Association between blood pressure and dementia in older adults: a cross-sectional study from China.

Background and aims: The association between blood pressure (BP) and dementia in older adults remains unclear, prompting this study to investigate the relationship between various BP indicators and dementia in this population. Methods: A cross-sectional survey was conducted in 2019, including 3,599 participants aged 65 years or older. The basic demographic characteristics of participants were collected. BP measurements and neuropsychological assessments were performed. From the systolic BP (SBP) and diastolic BP (DBP) values, mean arterial pressure (MAP), pulse pressure (PP) and blood pressure index (BPI) were calculated. Generalized additive models and logistic regression models were used to analyze the association between BP indicators and dementia. Results: Generalized additive models identified a U-shaped relationship between DBP and dementia, which was more significant in males and people 70 years of age and older. The optimal DBP associated with the lowest dementia risk was 85 mmHg. Logistic regression models revealed that compared to the DBP subgroup (80-89 mmHg), participants in the DBP < 80 mmHg subgroup and the DBP ≥100 mmHg subgroup had OR for dementia of 1.611 (95% CI: 1. 252-2.073, P < 0.001) and 1.423 (95% CI: 0.999-2.028, p = 0.050), respectively. A significant association was observed between BPI and dementia (OR:1.746 95% CI: 1.142-2.668, p = 0.010). Conclusion: In older adults, we found a U-shaped relationship between DBP and dementia, and a linear relationship between BPI and dementia. These results underscore the importance of considering DBP and BPI in BP management strategies for older adults to potentially prevent or delay dementia onset.

Blood-brain barrier breakdown in dementia with Lewy bodies.

BACKGROUND: Blood-brain barrier (BBB) dysfunction has been viewed as a potential underlying mechanism of neurodegenerative disorders, possibly involved in the pathogenesis and progression of Alzheimer's disease (AD). However, a relation between BBB dysfunction and dementia with Lewy bodies (DLB) has yet to be systematically investigated. Given the overlapping clinical features and neuropathology of AD and DLB, we sought to evaluate BBB permeability in the context of DLB and determine its association with plasma amyloid-ß (Aß) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: For this prospective study, we examined healthy controls (n = 24, HC group) and patients diagnosed with AD (n = 29) or DLB (n = 20) between December 2020 and April 2022. Based on DCE-MRI studies, mean rates of contrast agent transfer from intra- to extravascular spaces (Ktrans) were calculated within regions of interest. Spearman's correlation and multivariate linear regression were applied to analyze associations between Ktrans and specific clinical characteristics. RESULTS: In members of the DLB (vs HC) group, Ktrans values of cerebral cortex (p = 0.024), parietal lobe (p = 0.007), and occipital lobe (p = 0.014) were significantly higher; and Ktrans values of cerebral cortex (p = 0.041) and occipital lobe (p = 0.018) in the DLB group were significantly increased, relative to those of the AD group. All participants also showed increased Ktrans values of parietal ( ß  = 0.391; p = 0.001) and occipital ( ß  = 0.357; p = 0.002) lobes that were significantly associated with higher scores of the Clinical Dementia Rating, once adjusted for age and sex. Similarly, increased Ktrans values of cerebral cortex ( ß  = 0.285; p = 0.015), frontal lobe ( ß  = 0.237; p = 0.043), and parietal lobe ( ß = 0.265; p = 0.024) were significantly linked to higher plasma Aß1-42/Aß1-40 ratios, after above adjustments. CONCLUSION: BBB leakage is a common feature of DLB and possibly is even more severe than in the setting of AD for certain regions of the brain. BBB leakage appears to correlate with plasma Aß1-42/Aß1-40 ratio and dementia severity.

Prolonged elevated heart rate is association with adverse outcome in severe pulmonary embolism: A retrospective study.

BACKGROUND: Pulmonary embolism (PE) is a critical condition characterized by the obstruction of pulmonary arteries by thrombi, which significantly contributes to morbidity and mortality globally. Although prolonged elevated heart rate (peHR) is recognized as a risk factor for adverse outcomes in critically ill patients, its specific impact on severe PE has remained unexplored. METHODS: This retrospective cohort study analyzed data from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients diagnosed with PE were included in the study. peHR was defined as heart rates exceeding 100 beats per minute on at least 11 occasions within any 12-h interval. Cox proportional hazards regression models were used to evaluate the impact of peHR on 30-day and 90-day mortality rates, adjusting for a broad range of demographic and clinical variables. RESULTS: A total of 1248 patients were included in this study, of whom 540 exhibited peHR. These patients experienced significantly longer hospital and intensive care unit (ICU) stays, as well as higher mortality rates at both 30 days (25.93 % vs. 14.97 %, P < 0.001) and 90 days (33.89 % vs. 22.74 %, P < 0.001) compared to patients without peHR. Multivariate Cox regression analysis confirmed peHR as an independent predictor of increased mortality at 30 days (HR 1.56, 95 % CI 1.19-2.07; P = 0.0014) and 90 days (HR 1.66, 95 % CI 1.32-2.10; P < 0.001). CONCLUSION: peHR significantly worsens outcomes in severe PE patients, underscoring the need for stringent heart rate monitoring and management. These findings advocate for integrating heart rate control within management strategies for severe PE, potentially improving survival outcomes.

Synergistic Antimicrobial Mechanism of the Ultrashort Antimicrobial Peptide R3W4V with a Tadpole-like Conformation.

Antimicrobial peptides (AMPs) are promising candidates in combating multidrug-resistant microorganisms because of their unique mode of action. Among these peptides, ultrashort AMPs (USAMPs) possess sequences containing less than 10 amino acids and have some advantages over traditional AMPs. However, one of the main limitations of designing novel and highly active USAMPs is that their mechanism of action at the molecular level is not well-known. In this article, we report the antimicrobial mechanism of the USAMP verine (R3W4V) with high antibacterial activity against Escherichia coli. Here, by using well-tempered bias-exchange metadynamics simulations and long-time conventional molecular dynamics simulations, we evaluated whether verine exhibits the same antimicrobial mode of action as that of traditional AMPs. The single verine-membrane system exhibited a relatively flat surface with multiple shallow minima separated by very small energy barriers and adopted highly dynamic structural ensembles. Although the verine sequence is very short, it can still exist briefly in the center of the cell membrane in a transmembrane state. As the concentration of verine increased, the transmembrane conformation was relatively stabilized in the membrane center or proceeded toward the membrane bottom. The lipid bilayer membrane showed relatively large deformation, including the phospholipid head groups embedded inside the lipid hydrophobic center, accompanied by a flip-flop of some lipids. Simulation results indicated that verine has a specific mechanism of action different from that of traditional AMPs. Based on this antimicrobial mechanism of verine, we can design new high-potential USAMPs by enhancing the structural stability of the transmembrane state.

Development and validation of a nomogram for assessing survival in acute exacerbation of chronic obstructive pulmonary disease patients.

BACKGROUND: Early prediction of survival of hospitalized acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients is vital. We aimed to establish a nomogram to predict the survival probability of AECOPD patients. METHODS: Retrospectively collected data of 4601 patients hospitalized for AECOPD. These patients were randomly divided into a training and a validation cohort at a 6:4 ratio. In the training cohort, LASSO-Cox regression analysis and multivariate Cox regression analysis were utilized to identify prognostic factors for in-hospital survival of AECOPD patients. A model was established based on 3 variables and visualized by nomogram. The performance of the model was assesed by AUC, C-index, calibration curve, decision curve analysis in both cohorts. RESULTS: Coexisting arrhythmia, invasive mechanical ventilation (IMV) usage and lower serum albumin values were found to be significantly associated with lower survival probability of AECOPD patients, and these 3 predictors were further used to establish a prediction nomogram. The C-indexes of the nomogram were 0.816 in the training cohort and 0.814 in the validation cohort. The AUC in the training cohort was 0.825 for 7-day, 0.807 for 14-day and 0.825 for 21-day survival probability, in the validation cohort this were 0.796 for 7-day, 0.831 for 14-day and 0.841 for 21-day. The calibration of the nomogram showed a good goodness-of-fit and decision curve analysis showed the net clinical benefits achievable at different risk thresholds were excellent. CONCLUSION: We established a nomogram based on 3 variables for predicting the survival probability of AECOPD patients. The nomogram showed good performance and was clinically useful.

Simultaneous determination of 78 pesticide residues and 16 mycotoxins in tsampa by an improved QuEChERS method coupled with ultra performance liquid chromatography-tandem mass spectrometry.

Tsampa may contain pesticide residues and mycotoxins, which may pose a risk to human health. Currently, pesticide detection and mycotoxin detection are two independent experiments. To improve the efficiency of the analysis, a method based on QuEChERS combined with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the simultaneous determination of 78 pesticides and 16 mycotoxins in tsampa was developed. All the target compounds showed good linear correlation with correlation coefficients (R2) greater than 0.9990. The limits of detection (LODs) and limits of quantification (LOQs) were in the ranges of 0.10-3.00 µg kg-1 and 0.40-10.00 µg kg-1, respectively. The average recoveries of the pesticides and mycotoxins spiked at the 1, 2, and 10-fold LOQ were in the range of 73.0-115.2%, and the relative standard deviations (RSDs) were lower than 11.7%. This method was applied to 19 batches of real samples in which 32% of samples exceeded the maximum residue limits of the European Union involving aflatoxin G2, ochratoxin A, and hexaconazole. It proved to be excellent, efficient, greatly simplified, and highly applicable, which could reduce the workload and time significantly for the daily monitoring of the pesticides and mycotoxins in tsampa.

Surgical intervention of Lemierre's syndrome: a case report and review of the literature.

BACKGROUND: Lemierre's syndrome is a fatal and rare disease that is typically characterized by oropharyngeal infection and internal jugular vein thrombosis. Timely institution of appropriate antibiotics is the standard treatment. CASE PRESENTATION: The authors report a case of Lemierre's syndrome. A 67-year-old male patient of Han ethnicity in China suffered from a large inflammatory neck mass involving left internal jugular vein thrombosis diagnosed as Lemierre's syndrome and finally cured by surgical treatment. In addition, a literature review was carried out through PubMed using the terms "Lemierre's syndrome/disease and review, meta-analysis or retrospective study" and "Lemierre's syndrome/disease and internal jugular vein". This search yielded six articles that recorded surgical methods such as drainage, craniotomy, tooth extraction, and ligation of the occluded vein to give clinicians more ideas about the treatment of the Lemierre's syndrome. CONCLUSION: This is the first review to summarize the conditions under which surgical treatment are conducted. Additionally, this is the first report of such a large inflammatory neck mass that was completely cured by surgical resection and internal jugular vein ligation. The authors also offer several conclusions regarding surgical intervention in Lemierre's syndrome for the first time.

Revealing a Novel Methylated Integrin Alpha-8 Related to Extracellular Matrix and Anoikis Resistance Using Proteomic Analysis in the Immune Microenvironment of Lung Adenocarcinoma.

Genomic epigenetics of extracellular matrix (ECM) play an important role in lung adenocarcinoma (LUAD). Our study identified a signature of potential prognostic genes associated with ECM and constructed immune risk-related prognosis model in LUAD. We downloaded mRNAs transcriptome data, miRNAs expression data, and clinical patient information for LUAD based on The Cancer Genome Atlas. "Limma, clusterProfiler, ggplot2" R packages and GSEA were used to analyze meaningful genes and explore potential biological function. A competing endogenous RNA network was constructed to reveal the mechanism of ECM-related genes. Combined with clinical LUAD patients' characteristics, univariate and multivariate Cox regression analyses were used to build prognostic immune risk model. Next, we calculated AUC value of ROC curve, and explored survival probability of different risk groups. A total of 2966 mRNAs were differently expressed in LUAD samples and normal samples. Function enrichment analyses proved mRNAs were associated with many tumor pathways, such as cell adhesion, vascular smooth muscle contraction, and cell cycle. There were 18 mRNAs related to ECM receptor signaling pathway, and 7 mRNAs expressions were correlated with EGFR expression, but only 5mRNAs were associated with the long-term prognosis. Based on Integrin alpha-8 (ITGA8) molecule, we identified potential 3 miRNAs from several databases. The promoter of ITGA8 was higher-methylated and lower-expressed in LUAD. And lower-expressed group has poor prognosis for patients. 66 immunomodulators related to ITGA8 were performed to construct immune correlation prediction model (p < 0.05). Comprehensive analyses of ITGA8 revealed it combined focal adhesion kinase to activate PI3K/AKT signaling pathway to influence the occurrence and development of LUAD. A novel immune prognostic model about ITGA8 was constructed and verified in LUAD patients. Combined with non-coding genes and genomic epigenetics, identification of potential biomarkers provided new light on therapeutic strategy for clinical patients.

Spontaneous uterine rupture with amniotic sac protrusion during the third trimester of a unicornuate uterus pregnancy: A rate case report.

RATIONALE: Uterine rupture is an obstetrical emergency associated with severe maternal and fetal mortality. It is rare in the unscarred uterus of a primipara. PATIENT CONCERNS: A 25-year-old woman in her 38th week of gestation presented with slight abdominal pain of sudden onset 10 hours before. An emergency cesarean section was done. After surgery, the patient and the infant survived. DIAGNOSES: With slight abdominal pain of clinical signs, ultrasound examination showed that the amniotic sac was found in the peritoneal cavity with a rupture of the uterine fundus. INTERVENTIONS: Uterine repair and right salpingectomy. OUTCOMES: After surgery, the patient and the infant survived. The newborn weighed 2600 g and had an Apgar score of 10 points per minute. Forty-two days after delivery, the uterus recovered well. LESSONS: Spontaneous uterine rupture should be considered in patients even without acute pain, regardless of gestational age, and pregnancy with abdominal cystic mass should consider the possibility of uterine rupture.

The association between chronic obstructive pulmonary disease and autoimmune diseases: a bidirectional Mendelian randomization study.

Objective: Observational studies have reported that chronic obstructive pulmonary disease (COPD) is often accompanied by autoimmune diseases, but the causal relationships between them remain uncertain. In this Mendelian study, we aimed to investigate the potential causal relationship between COPD and four common autoimmune diseases. Methods: We conducted an analysis of summary data on COPD and autoimmune disease using publicly available genome-wide association studies (GWAS) summary data. We initially employed the inverse- variance weighted method as the primary approach to establish the causal impact of COPD on autoimmune diseases in the sample and conducted additional sensitivity analyses to examine the robustness of the results. Subsequently, we performed reverse Mendelian randomization (MR) analyses for the four autoimmune diseases. Finally, the potential for bidirectional causal relationships was assessed. Results: Our MR analysis revealed no significant causal relationship between COPD and any of the studied autoimmune diseases. However, reverse MR results indicated a significant association between rheumatoid arthritis (RA), osteoarthritis (OA) and the risk of developing COPD, with respective odds ratios (OR) of 377.313 (95% CI, 6.625-21487.932, P = 0.004) for RA and 11.097 (95% CI, 1.583-77.796, P = 0.015) for OA. Sensitivity analyses confirmed the robustness of the results. Conclusion: Our findings support a potential causal relationship between autoimmune diseases and COPD, highlighting the importance of considering comorbidities in clinical management of COPD.

Mediating Effect of Tobacco Dependence on the Association Between Maternal Smoking During Pregnancy and Chronic Obstructive Pulmonary Disease: Case-Control Study.

BACKGROUND: Maternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. OBJECTIVE: This study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). METHODS: This case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was <0.7 in a postbronchodilator pulmonary function test according to the 2017 Global Initiative for Chronic Obstructive Lung Disease criteria. Logistic regression was used to examine the correlation between MSDP and COPD, adjusting for age, sex, BMI, educational attainment, place of residence, ethnic background, occupation, childhood passive smoking, residential fine particulate matter, history of childhood pneumonia or bronchitis, average annual household income, and medical history (coronary heart disease, hypertension, and diabetes). Mediation analysis examined TD as a potential mediator in the link between MSDP and COPD risk. The significance of the indirect effect was assessed through 1000 iterations of the "bootstrap" method. RESULTS: The study included 5943 participants (2991 with COPD and 2952 controls). Mothers of the COPD group had higher pregnancy smoking rates (COPD: n=305, 10.20%; controls: n=211, 7.10%; P<.001). TD was more prevalent in the COPD group (COPD: n=582, 40.40%; controls: n=478, 33.90%; P<.001). After adjusting for covariates, MSDP had a significant effect on COPD (ß=.097; P<.001). There was an association between MSDP and TD (ß=.074; P<.001) as well as between TD and COPD (ß=.048; P=.007). Mediation analysis of TD in the MSDP-COPD association showed significant direct and indirect effects (direct: ß=.094; P<.001 and indirect: ß=.004; P=.03). The indirect effect remains present in the smoking population (direct: ß=.120; P<.001 and indirect: ß=.002; P=.03). CONCLUSIONS: This study highlighted the potential association between MSDP and the risk of COPD in offspring, revealing the mediating role of TD in this association. These findings contribute to a deeper understanding of the impact of prenatal tobacco exposure on lung health, laying the groundwork for the development of relevant prevention and treatment strategies.

Characterization of de novo Dementia with Lewy Body with different duration of rapid eye movement sleep behavior disorder.

BACKGROUND: Cognitive disorder, parkinsonism, autonomic dysfunction (AuD) and rapid eye movement sleep behavior disorder (RBD) can occur prior to or simultaneously with Dementia with Lewy Body (DLB) onset. RBD is generally linked with progressive neurodegenerative traits. However, associations between RBD with DLB, RBD without DLB, and RBD duration effects on DLB symptoms remain unclear. OBJECTIVES: To examine DLB symptom frequency and subtypes in RBD, and explore the effects of different RBD onset times on symptoms in de novo DLB patients. METHODS: In this multicenter investigation, we consecutively recruited 271 de novo DLB patients. All had standardized clinical and comprehensive neuropsychological evaluations. Subgroup analyses, performed based on the duration of RBD confirmed by polysomnography before the DLB diagnosis, we compared the proportion of patients with cognitive impairment, parkinsonism, and AuD features between groups. RESULTS: Parkinsonism and AuD incidences were significantly elevated in DLB patients with RBD when compared with patients without RBD. Subgroup analyses indicated no significant differences in parkinsonism between DLB patients who developed RBD ≥10 years prior to the DLB diagnosis and DLB patients without RBD. The incidence of non-tremor-predominant parkinsonism and AuD was significantly higher in DLB patients whose RBD duration before the DLB diagnosis was <10 years when compared with DLB patients without RBD. CONCLUSIONS: We identified significant symptom and phenotypic variability between DLB patients with and without RBD. Also, different RBD duration effects before the DLB diagnosis had a significant impact on symptomatic phenotypes, suggesting the existence of a slowly progressive DLB neurodegenerative subtype.

First-principles study of the electronic structure and optical properties of C-doped SnS2.

CONTEXT: Density functional theory (DFT) was used to investigate the effects of varying carbon doping concentrations on the electronic and optical properties of SnS2-doped systems. The findings show that a doping concentration of 3.7% in SnS2 results in the highest structural stability and the lowest formation energy. A pure SnS2 monolayer is an indirect bandgap semiconductor, and the result reveals that increasing carbon doping correlates with a gradual reduction in the system's bandgap. The density of states analysis reveals that the valence band comprises C-2p, S-3p, and Sn-5p orbitals, whereas the conduction band consists of S-3p, Sn-5 s, and C-2p orbitals. Furthermore, doping concentration appears to cause a redshift in both the absorption coefficient and reflection peaks, which both decrease as doping concentration increases. METHODS: The calculations for this study were performed using DFT within the CASTEP module of Materials Studio Segall et al. J Phys: Condens Matter 14(11):2717, 2002. The system parameters and structures were optimized to determine the electronic structure and optical properties. Geometric optimization and calculations were carried out with the generalized gradient approximation plane-wave pseudopotential method and the Perdew-Burke-Ernzerhof functional Perdew et al. Phys Rev Lett 80(4):891-891, 1998. The parameters for structural optimization included a plane-wave expansion cutoff energy set at 500 eV and a k-point mesh of 6 × 6 × 1 for Brillouin zone integration. The electronic convergence criteria were established at 1.0 × 10-5 eV/atom for the unit cell energy and 1.0 × 10-6 eV/atom for self-consistency. The internal stress deviation was maintained below 0.05 GPa, the atomic force interactions were kept under 0.03 eV/Å, and atomic displacements during geometric optimization were confined to less than 0.001 Å. To calculate the properties of the SnS2 monolayer, a vacuum spacing of 15 Å along the z-axis was introduced to prevent interactions between adjacent layers.

Molecular mechanism of calcitriol enhances membrane water permeability.

Helicobacter pylori (H. pylori) exhibits a unique membrane lipid composition, including dimyristoyl phosphatidylethanolamine (DMPE) and cholesterol, unlike other Gram-negative bacteria. Calcitriol has antimicrobial activity against H. pylori, but cholesterol enhances antibiotics resistance in H. pylori. This study explored the changes in membrane structure and the molecular mechanisms of cholesterol/calcitriol translocation using well-tempered metadynamics (WT-MetaD) simulations and microsecond conventional molecular dynamics (CMD) simulations. Calcitriol facilitated water transport across the membrane, while cholesterol had the opposite effect. The differing effects might result from the tail 25-hydroxyl group and a wider range of orientations of calcitriol in the DMPE/dimyristoyl phosphatidylglycerol (DMPG) (3:1) membrane. Calcitriol moves across the bilayer center without changing its orientation along the membrane Z-axis, becomes parallel to the membrane surface at the membrane-water interface, and then rotates approximately 90° in this interface. The translocation mechanism of calcitriol is quite different from the flip-flop of cholesterol. Moreover, calcitriol crossed from one layer to another more easily than cholesterol, causing successive perturbations to the hydrophobic core and increasing water permeation. These results improve our understanding of the relationship between cholesterol/calcitriol concentrations and the lipid bilayer structure and the role of lipid composition in water permeation.

Toward Reagent-Free Discrimination of Alzheimer's Disease Using Blood Plasma Spectral Digital Biomarkers and Machine Learning.

BACKGROUND: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease. The detection of early-stage AD is particularly desirable because it would allow early intervention. However, a minimally invasive, low-cost, and accurate discrimination or diagnostic method for AD is especially difficult in the earliest stage of AD. OBJECTIVE: The aim of this research is to discover blood plasma spectral digital biomarkers of AD, develop a novel intelligent method for the discrimination of AD and accelerate the translation of Fourier transform infrared (FTIR) spectral-based disease discrimination methods from the laboratory to clinical practice. METHODS: Since vibration spectroscopy can provide the structure and chemical composition information of biological samples at the molecular level, we investigated the potential of FTIR spectral biomarkers of blood plasma to differentiate between AD patients and healthy controls. Combined with machine learning technology, we designed a hierarchical discrimination system that provides reagent-free and accurate AD discrimination based on blood plasma spectral digital biomarkers of AD. RESULTS: Accurate segregation between AD patients and healthy controls was achieved with 89.3% sensitivity and 85.7% specificity for early-stage AD patients, 92.8% sensitivity and 87.5% specificity for middle-stage AD patients, and 100% sensitivity and 100% specificity for late-stage AD patients. CONCLUSIONS: Our results show that blood plasma spectral digital biomarkers hold great promise as discrimination markers of AD, indicating the potential for the development of an inexpensive, reagent-free, and less laborious clinical test. As a result, our research outcome will accelerate the clinical application of spectral digital biomarkers and machine learning.

Serum lipid levels are associated with orthostatic hypotension in multiple system atrophy patients.

OBJECTIVES: Orthostatic hypotension (OH) is one of the most important autonomic features of multiple system atrophy (MSA). This study was established to confirm the correlation between lipid levels and OH in MSA. METHODS: A total of 580 patients with probable or possible MSA from neurological wards in six hospitals in Tianjin, Beijing, Hebei Province, and Henan Province, China, were included in this study. The tilt test or stand test was used to assess the severity of OH. Lipid contents, including total cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), and triglyceride were evaluated. RESULTS: Serum levels of total cholesterol, LDL-C, and triglyceride in MSA-OH patients were significantly lower than those in MSA without OH. The risks of OH were significantly higher in the lowest quartiles of triglyceride and LDL-C than in the highest quartiles, after adjusting for confounders (OR = 2.17, 95% CI: 1.23-3.82, P = 0.008 and OR = 2.02, 95% CI: 1.16-3.47, P = 0.012). The risk of severe OH was significantly higher in the lowest quartile and the second quartile of triglyceride than in the highest quartile after adjusting for confounders (OR = 2.16, 95% CI: 1.20-3.87, P = 0.010 and OR = 2.25, 95% CI: 1.24-4.07, P = 0.007). Moreover, the risk of OH was significantly higher in the lowest quartile, and the third quartile of TC than in the highest quartile after adjusting for confounders (OR = 2.04, 95% CI: 1.18-3.52, P = 0.010 and OR = 2.06, 95% CI: 1.19-3.56, P = 0.010). CONCLUSION: Low levels of TC, LDL-C, and triglyceride increased the risk of OH in MSA. A low level of triglyceride predicted severe OH in MSA.

White matter hyperintensities in cognitive impairment with Lewy body disease: a multicentre study.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) are associated with cognitive deficits and worse clinical outcomes in dementia, but rare studies have been carried out of cognitive impairment in Lewy body disease (CI-LB) patients. The objective was to investigate the associations between WMHs and clinical manifestations in patients with CI-LB. METHODS: In this retrospective multicentre cohort study, 929 patients (486 with dementia with Lewy bodies [DLB], 262 with Parkinson's disease dementia [PDD], 74 with mild cognitive impairment [MCI] with Lewy bodies [MCI-LB] and 107 with Parkinson's disease with MCI [PD-MCI]) were analysed from 22 memory clinics between January 2018 and June 2022. Demographic and clinical data were collected by reviewing medical records. WMHs were semi-quantified according to the Fazekas method. Associations between WMHs and clinical manifestations were investigated by multivariate linear or logistic regression models. RESULTS: Dementia with Lewy bodies patients had the highest Fazekas scores compared with PDD, MCI-LB and PD-MCI. Multivariable regressions showed the Fazekas score was positively associated with the scores of Unified Parkinson's Disease Rating Scale Part III (p = 0.001), Hoehn-Yahn stage (p = 0.004) and total Neuropsychiatric Inventory (p = 0.001) in MCI-LB and PD-MCI patients. In patients with DLB and PDD, Fazekas scores were associated with the absence of rapid eye movement sleep behaviour disorder (p = 0.041) and scores of Unified Parkinson's Disease Rating Scale Part III (p < 0.001), Hoehn-Yahn stage (p < 0.001) and the Montreal Cognitive Assessment (p = 0.014). CONCLUSION: White matter hyperintensity burden of DLB was higher than for PDD, MCI-LB and PD-MCI. The greater WMH burden was significantly associated with poorer cognitive performance, worse motor function and more severe neuropsychiatric symptoms in CI-LB.

Cleft palate in fetuses: feasibility of early diagnosis by Crystal and Realistic Vue rendering 3D ultrasound technology in the first trimester.

Objectives: This study aimed to evaluate the feasibility of direct visualization of a normal fetal palate and detect cleft palate in the first trimester with a novel three-dimensional ultrasound (3D US) technique, Crystal and Realistic Vue (CRV) rendering technology. Methods: Two-dimensional (2D) images and 3D volumes of healthy and cleft palate fetuses at 11-13+6 weeks were obtained prospectively. 2D ultrasound views included the coronal view of the retronasal triangle and the midsagittal view of the face. 3D-CRV views were analyzed by multiplanar mode display. The pregnancy outcomes of all fetuses were determined during the follow-up period. Results: In our study, 124 fetuses were recruited, including 100 healthy fetuses and 24 cleft palate fetuses. The cleft palate with lip was observed in 23 fetuses (bilateral in 15, unilateral in 6, median in 2), and one cleft palate was only found in the abnormal group. The bilateral (n = 12) and median (n = 2) cleft palates with lips and the cleft palate alone (n = 1) were associated with other anatomical or chromosomal abnormalities, and one unilateral cleft palate with cleft lip had concomitant NT thickening. In the cleft palate fetus group, 16 fetuses suffered intrauterine death, which was associated with other structural or chromosomal abnormalities in 14 fetuses, seven cases were terminated after consultation, and one was delivered at term. The coronal view of the retronasal triangle and the midsagittal view was easily obtained in all fetuses. 3D-CRV images of palatal parts were clearly obtained in all cases. Unilateral, bilateral, and median cleft palates with cleft lips were visually demonstrated and classified by the 3D-CRV technique. Conclusion: It is feasible to identify the palate by 3D-CRV in the first trimester in both healthy and cleft palate fetuses. Together with 2D ultrasonography as a complementary diagnostic tool, 3D-CRV is helpful in classifying the cleft palate with a reasonable degree of certainty.

Comprehensive analyses of genome-wide methylation and RNA epigenetics identify prognostic biomarkers, regulating the tumor immune microenvironment in lung adenocarcinoma.

The aim of our study was to identify a signature of immune-regulated molecules and reveal its prognostic role in lung adenocarcinoma (LUAD). We downloaded RNA-Sequencing data and DNA methylation data from the Gene Expression Omnibus (GEO) database. GEO2R was used to analyze differentially expressed mRNAs (DEmRNAs). we used "factoextra" R package to do the principal component analysis (PCA) of DEmRNAs. "Limma" R package was used to identify DEmRNAs, differentially expressed miRNAs (DEmiRNAs), differentially expressed lncRNAs (DElncRNAs) from The Cancer Genome Atlas (TCGA) database. Three R packages "org.Hs.eg.db", "clusterProfiler", "ggplot2″ were used to show enrichment results. Considering about methylation and mutation data, TEK and SOX17 mediated cancer signaling pathways. Through tumor-immune system interactions database (TISIDB) and Tumor Immune Estimation Resource (TIMER), higher methylated and lower expressed TEK may act as a prognostic marker, regulating the tumor immunity in LUAD. Through four databases (MEXPRESS, DNMIVD, MethSurv, Firehose), we further verified the methylation (P = 2.33e-23) and mutation about TEK. A signature of immune-associated TEK to predict survival of LUAD patients was validated. Prognostic, methylation, immune microenvironment analysis showed new light on potential novel therapeutic targets in LUAD.