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Though previous studies revealed the potential associations of elevated levels of plasma fibrinogen with dementia, there is still limited understanding regarding the influence of Alzheimer's disease (AD) biomarkers on these associations. We sought to investigate the interrelationships among fibrinogen, cerebrospinal fluid (CSF) AD biomarkers, and cognition in non-demented adults. We included 1996 non-demented adults from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study and 337 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The associations of fibrinogen with AD biomarkers and cognition were explored using multiple linear regression models. The mediation analyses with 10 000 bootstrapped iterations were conducted to explore the mediating effects of AD biomarkers on cognition. In addition, interaction analyses and subgroup analyses were conducted to assess the influence of covariates on the relationships between fibrinogen and AD biomarkers. Participants exhibiting low Aβ42 were designated as A+, while those demonstrating high phosphorylated tau (P-tau) and total tau (Tau) were labeled as T+ and N+, respectively. Individuals with normal measures of Aβ42 and P-tau were categorized as the A-T- group, and those with abnormal levels of both Aβ42 and P-tau were grouped under A+T+. Fibrinogen was higher in the A+ subgroup compared to that in the A- subgroup (p = 0.026). Fibrinogen was higher in the A+T+ subgroup compared to that in the A-T- subgroup (p = 0.011). Higher fibrinogen was associated with worse cognition and Aβ pathology (all p < 0.05). Additionally, the associations between fibrinogen and cognition were partially mediated by Aβ pathology (mediation proportion range 8%-28%). Interaction analyses and subgroup analyses showed that age and ApoE ε4 affect the relationships between fibrinogen and Aβ pathology. Fibrinogen was associated with both cognition and Aβ pathology. Aβ pathology may be a critical mediator for impacts of fibrinogen on cognition., (© 2024 International Society for Neurochemistry.)

Physical frailty and genetic factors are both risk factors for increased dementia; nevertheless, the joint effect remains unclear. This study aimed to investigated the long-term relationship between physical frailty, genetic risk, and dementia incidence. A total of 274,194 participants from the UK Biobank were included. We applied Cox proportional hazards regression models to estimate the association between physical frailty and genetic and dementia risks. Among the participants (146,574 females [53.45%]; mean age, 57.24 years), 3,353 (1.22%) new-onset dementia events were recorded. Compared to non-frailty, the hazard ratio (HR) for dementia incidence in prefrailty and frailty was 1.396 (95% confidence interval [CI], 1.294-1.506, P < 0.001) and 2.304 (95% CI, 2.030-2.616, P < 0.001), respectively. Compared to non-frailty and low polygenic risk score (PRS), the HR for dementia risk was 3.908 (95% CI, 3.051-5.006, P < 0.001) for frailty and high PRS. Furthermore, among the participants, slow walking speed (HR, 1.817; 95% CI, 1.640-2.014, P < 0.001), low physical activity (HR, 1.719; 95% CI, 1.545-1.912, P < 0.001), exhaustion (HR, 1.670; 95% CI, 1.502-1.856, P < 0.001), low grip strength (HR, 1.606; 95% CI, 1.479-1.744, P < 0.001), and weight loss (HR, 1.464; 95% CI, 1.328-1.615, P < 0.001) were independently associated with dementia risk compared to non-frailty. Particularly, precise modulation for different dementia genetic risk populations can also be identified due to differences in dementia risk resulting from the constitutive pattern of frailty in different genetic risk populations. In conclusion, both physical frailty and high genetic risk are significantly associated with higher dementia risk. Early intervention to modify frailty is beneficial for achieving primary and precise prevention of dementia, especially in those at high genetic risk., (© 2024. The Author(s).)

Background: Anti-synthetase syndrome (AS) is a rare autoimmune idiopathic inflammatory myopathy (IIM) with diverse manifestations, including arthritis, interstitial lung disease (ILD), Raynaud's phenomenon, unexplained persistent fever, and mechanic's hands., Case Presentation: We present the case of a 72-year-old woman, previously healthy, who was admitted to our hospital for treatment of cough and rapid breathing. The patient had elevated white blood cells and C-reactive protein, and tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). She was initially diagnosed with community-acquired pneumonia and received tamoxifen for anti-infection treatment, but her dystonia worsened. She eventually required non-invasive ventilator support, tested positive for SARS-Cov-2 again, and started antiviral therapy, corticosteroids to reduce alveolar effusion, anticoagulation, and other treatments. However, her condition continued to deteriorate, with the lowest oxygenation index reaching only 80mmHg. Ultimately, she underwent tracheal intubation and mechanical ventilation. Chest CT revealed rapid progressive interstitial changes in her lungs, and her hands showed noticeable fraternization changes. At this point, we suspected that the novel coronavirus infection might be associated with autoimmune diseases. The patient's autoimmune antibody spectrum showed positive results for anti-recombinant RO-52 antibody and myositis-specific antibody anti-alanyl tRNA synthetase (anti-PL-12). The patient was treated with dexamethasone sodium phosphate for anti-inflammatory and anti-fibrotic effects. After successful extubation, the patient was discharged with only oral prednisone tablets at a dose of 30 mg., Conclusions: This case presents an early diagnosis and successful treatment of anti-synthetase syndrome combined with SARS-Cov-2 infection, emphasizing the importance of comprehensive physical examination. Additionally, it highlights the rapid progression of interstitial lung disease under SARS-Cov-2 infection, which is often difficult to distinguish on imaging. In cases where treatment for SARS-Cov-2 infection is ineffective, early screening for autoimmune diseases is recommended. As there is currently no standardized method for treating AS-ILD, the successful treatment of this case provides a reference for clinical research on anti-synthetase syndrome in the later stage., (© 2024. The Author(s).)

Background: It has been reported that the risk of Alzheimer's disease (AD) could be predicted by the Australian National University Alzheimer Disease Risk Index (ANU-ADRI) scores. However, among non-demented Chinese adults, the correlations of ANU-ADRI scores with cerebrospinal fluid (CSF) core biomarkers and cognition remain unclear., Methods: Individuals from the Chinese Alzheimer's Biomarker and LifestyLE (CABLE) study were grouped into three groups (low/intermediate/high risk groups) based on their ANU-ADRI scores. The multiple linear regression models were conducted to investigate the correlations of ANU-ADRI scores with several biomarkers of AD pathology. Mediation model and structural equation model (SEM) were conducted to investigate the mediators of the correlation between ANU-ADRI scores and cognition., Results: A total of 1078 non-demented elders were included in our study, with a mean age of 62.58 (standard deviation [SD] 10.06) years as well as a female proportion of 44.16% (n = 476). ANU-ADRI scores were found to be significantly related with MMSE (β = -0.264, P < 0.001) and MoCA (β = -0.393, P < 0.001), as well as CSF t-tau (β = 0.236, P < 0.001), p-tau (β = 0.183, P < 0.001), and t-tau/Aβ42 (β = 0.094, P = 0.005). Mediation analyses indicated that the relationships of ANU-ADRI scores with cognitive scores were mediated by CSF t-tau or p-tau (mediating proportions ranging from 4.45% to 10.50%). SEM did not reveal that ANU-ADRI scores affected cognition by tau-related pathology and level of CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2)., Conclusion: ANU-ADRI scores were associated with cognition and tau pathology. We also revealed a potential pathological mechanism underlying the impact of ANU-ADRI scores on cognition., (© 2024. The Author(s).)

Background: Antipsychotics (APs) are among the most widely prescribed medications, and have been shown to cause cognitive decline. But previous studies on their effects on dementia risk are controversial and scarce. We aimed to examine the relationships of APs exposure with the risk of dementia., Methods: Data were obtained from a prospective cohort of 415,100 UK Biobank (UKB) participants. We investigated the effects of APs exposure and their various classes on dementia risk by using multivariable Cox proportional hazard models and further the dose-response effects of oral APs., Results: After a mean follow-up of 8.64 years, 5235 (1.3 %) participants developed all-cause dementia (ACD), among whom 2313 (0.6 %) developed Alzheimer's disease (AD), and 1213 (0.3 %) developed vascular dementia (VaD). Exposure to any APs conferred increased risks of ACD (HR: 1.33, 95 % CI = 1.17-1.51, P < 0.001) and VaD (HR: 1.90, 95 % CI = 1.51-2.40, P < 0.001), but not AD (HR: 1.22, 95 % CI = 1.00-1.48, P = 0.051). Cumulative dose-response relationships of oral APs with the risks of ACD and VaD were observed (P for trend, P < 0.05)., Limitations: Our study is observational and does not show evidence of causality. Since there are relatively few cases of dementia in the UKB, APs exposure may be higher than estimated in our study., Conclusions: APs exposure increased the risk of developing dementia. Dose-response relationships were found between oral APs and dementia risk. Efforts to raise awareness of doctors and patients about this potential drug-related risk are critical to reducing APs use., Competing Interests: Declaration of competing interest The authors declare that they have no financial disclosures and competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Cardiometabolic multimorbidity is associated with an increased risk of dementia, but the pathogenic mechanisms linking them remain largely undefined. We aimed to assess the associations of cardiometabolic multimorbidity with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology to enhance our understanding of the underlying mechanisms linking cardiometabolic multimorbidity and AD., Methods: This study included 1464 cognitively intact participants from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database. Cardiometabolic diseases (CMD) are a group of interrelated disorders such as hypertension, diabetes, heart diseases (HD), and stroke. Based on the CMD status, participants were categorized as CMD-free, single CMD, or CMD multimorbidity. CMD multimorbidity is defined as the coexistence of two or more CMDs. The associations of cardiometabolic multimorbidity and CSF biomarkers were examined using multivariable linear regression models with demographic characteristics, the APOE ε4 allele, and lifestyle factors as covariates. Subgroup analyses stratified by age, sex, and APOE ε4 status were also performed., Results: A total of 1464 individuals (mean age, 61.80 years; age range, 40-89 years) were included. The markers of phosphorylated tau-related processes (CSF P-tau181: β = 0.165, P = 0.037) and neuronal injury (CSF T-tau: β = 0.065, P = 0.033) were significantly increased in subjects with CMD multimorbidity (versus CMD-free), but not in those with single CMD. The association between CMD multimorbidity with CSF T-tau levels remained significant after controlling for Aβ42 levels. Additionally, significantly elevated tau-related biomarkers were observed in patients with specific CMD combinations (i.e., hypertension and diabetes, hypertension and HD), especially in long disease courses., Conclusions: The presence of cardiometabolic multimorbidity was associated with tau phosphorylation and neuronal injury in cognitively normal populations. CMD multimorbidity might be a potential independent target to alleviate tau-related pathologies that can cause cognitive impairment., (© 2024. The Author(s).)

Background: Blood-based biomarkers for dementia are gaining attention due to their non-invasive nature and feasibility in regular healthcare settings. Here, we explored the associations between 249 metabolites with all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VaD) and assessed their predictive potential., Methods: This study included 274,160 participants from the UK Biobank. Cox proportional hazard models were employed to investigate longitudinal associations between metabolites and dementia. The importance of these metabolites was quantified using machine learning algorithms, and a metabolic risk score (MetRS) was subsequently developed for each dementia type. We further investigated how MetRS stratified the risk of dementia onset and assessed its predictive performance, both alone and in combination with demographic and cognitive predictors., Results: During a median follow-up of 14.01 years, 5274 participants developed dementia. Of the 249 metabolites examined, 143 were significantly associated with incident ACD, 130 with AD, and 140 with VaD. Among metabolites significantly associated with dementia, lipoprotein lipid concentrations, linoleic acid, sphingomyelin, glucose, and branched-chain amino acids ranked top in importance. Individuals within the top tertile of MetRS faced a significantly greater risk of developing dementia than those in the lowest tertile. When MetRS was combined with demographic and cognitive predictors, the model yielded the area under the receiver operating characteristic curve (AUC) values of 0.857 for ACD, 0.861 for AD, and 0.873 for VaD., Conclusions: We conducted the largest metabolome investigation of dementia to date, for the first time revealed the metabolite importance ranking, and highlighted the contribution of plasma metabolites for dementia prediction., (© 2024. The Author(s).)

Inconsistent findings exist regarding the potential association between polluted air and Parkinson's disease (PD), with unclear insights into the role of inherited sensitivity. This study sought to explore the potential link between various air pollutants and PD risk, investigating whether genetic susceptibility modulates these associations. The population-based study involved 312,009 initially PD-free participants with complete genotyping data. Annual mean concentrations of PM 2.5 , PM 10 , NO 2 , and NO x were estimated, and a polygenic risk score (PRS) was computed to assess individual genetic risks for PD. Cox proportional risk models were employed to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between ambient air pollutants, genetic risk, and incident PD. Over a median 12.07-year follow-up, 2356 PD cases (0.76%) were observed. Compared to the lowest quartile of air pollution, the highest quartiles of NO 2 and PM 10 pollution showed HRs and 95% CIs of 1.247 (1.089-1.427) and 1.201 (1.052-1.373) for PD incidence, respectively. Each 10 μg/m 3 increase in NO 2 and PM 10 yielded elevated HRs and 95% CIs for PD of 1.089 (1.026-1.155) and 1.363 (1.043-1.782), respectively. Individuals with significant genetic and PM 10 exposure risks had the highest PD development risk (HR: 2.748, 95% CI: 2.145-3.520). Similarly, those with substantial genetic and NO 2 exposure risks were over twice as likely to develop PD compared to minimal-risk counterparts (HR: 2.414, 95% CI: 1.912-3.048). Findings suggest that exposure to air contaminants heightens PD risk, particularly in individuals genetically predisposed to high susceptibility., (© 2024. The Author(s).)

Object: The study aims to determine whether multimorbidity status is associated with cerebrospinal fluid (CSF) biomarkers for neurodegenerative disorders., Methods: A total of 827 patients were enrolled from the Parkinson's Progression Markers Initiative (PPMI) database, including 638 patients with early-stage Parkinson's disease (PD) and 189 healthy controls (HCs). Multimorbidity status was evaluated based on the count of long-term conditions (LTCs) and the multimorbidity pattern. Using linear regression models, cross-sectional and longitudinal analyses were conducted to assess the associations of multimorbidity status with CSF biomarkers for neurodegenerative disorders, including α-synuclein (αSyn), amyloid-β 42 (Aβ 42 ), total tau (t-tau), phosphorylated tau (p-tau), glial fibrillary acidic protein (GFAP), and neurofilament light chain protein (NfL)., Results: At baseline, the CSF t-tau (p = 0.010), p-tau (p = 0.034), and NfL (p = 0.049) levels showed significant differences across the three categories of LTC counts. In the longitudinal analysis, the presence of LTCs was associated with lower Aβ 42 (β < -0.001, p = 0.020), and higher t-tau (β = 0.007, p = 0.026), GFAP (β = 0.013, p = 0.022) and NfL (β = 0.020, p = 0.012); Participants with tumor/musculoskeletal/mental disorders showed higher CSF levels of t-tau (β = 0.016, p = 0.011) and p-tau (β = 0.032, p = 0.044) than those without multimorbidity., Conclusion: Multimorbidity, especially severe multimorbidity and the pattern of mental/musculoskeletal/ tumor disorders, was associated with CSF biomarkers for neurodegenerative disorders in early-stage PD patients, suggesting that multimorbidity might play a crucial role in aggravating neuronal damage in neurodegenerative diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Frailty is a vulnerability state increasing the risk of many adverse health outcomes, but little is known about the effects of frailty on neuropsychiatric health., Objective: To explore the associations between frailty and the risk of neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD), especially in its different clinical stages., Methods: We included 2,155 individuals assessed using modified frailty index-11 (mFI-11), Neuropsychiatric Inventory (NPI) and Neuropsychiatric Inventory Questionnaire (NPI-Q) in the Alzheimer's Disease Neuroimaging Initiative (ADNI). The relationships between frailty and NPSs were explored with logistic regression models and Cox proportional hazard regression models. Causal mediation analyses were conducted to explore the mediation factors between frailty and NPSs., Results: Among mild cognitive impairment (MCI) participants, frailty was cross-sectionally associated with an increased risk of apathy, and longitudinally associated with increased risk of depression and apathy. Among AD participants, frailty was cross-sectionally associated with increased risk of depression and anxiety, and longitudinally associated with an increased risk of apathy. Among participants with cognitive progression, frailty was associated with increased risk of depression and apathy. In MCI participants, the influence of frailty on NPSs was partially mediated by hippocampus volume, whole brain volume, and monocytes, with mediating proportions ranging from 8.40% to 9.29%., Conclusions: Frailty was associated with NPSs such as depression, anxiety, and apathy among MCI, AD, and cognitive progression participants. Atrophy of the hippocampus and whole brain, as well as peripheral immunity may be involved in the potential mechanisms underlying the above associations.

The relationship between liver dysfunction and dementia has been researched extensively but remains poorly understood. In this study, we investigate the longitudinal and cross-sectional associations between liver function and liver diseases and risk of incident dementia, impaired cognition, and brain structure abnormalities using Cox proportion hazard model and linear regression model. 431 699 participants with a mean of 8.65 (standard deviation [SD] 2.61) years of follow-up were included from the UK Biobank; 5542 all-cause dementia (ACD), 2427 Alzheimer's disease (AD), and 1282 vascular dementia (VaD) cases were documented. We observed that per SD decreases in alanine transaminase (ALT; hazard ratio [HR], 0.917; P FDR  <0.001) and per SD increases in aspartate aminotransferase (AST; HR, 1.048; P FDR  = 0.010), AST to ALT ratio (HR, 1.195; P FDR  <0.001), gamma-glutamyl transpeptidase (GGT; HR, 1.066; P FDR  <0.001), alcoholic liver disease (ALD; HR, 2.872; P FDR  <0.001), and fibrosis and cirrhosis of liver (HR, 2.285; P FDR  = 0.002), being significantly associated with a higher risk of incident ACD. Restricted cubic spline models identified a strong U-shaped association between Alb and AST and incident ACD (P nonlinear  <0.05). Worse cognition was positively correlated with AST, AST to ALT ratio, direct bilirubin (DBil), and GGT; negatively correlated with ALT, Alb, and total bilirubin (TBil); and ALD and fibrosis and cirrhosis of liver (P FDR  <0.05). Moreover, changes in ALT, GGT, AST to ALT ratio, and ALD were significantly associated with altered cortical and subcortical regions, including hippocampus, amygdala, thalamus, pallidum, and fusiform (P FDR  <0.05). In sensitivity analysis, metabolic dysfunction-associated steatotic liver disease (MASLD) was associated with the risk of ACD and brain subcortical changes. Our findings provide substantial evidence that liver dysfunction may be an important factor for incident dementia. Early intervention in the unhealthy liver may help prevent cognitive impairment and dementia incidence., (© 2023 International Society for Neurochemistry.)

Background: Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) risk score serves as a credible predictor of an individual's risk of dementia. However, studies on the link of the CAIDE score to Alzheimer's disease (AD) pathology are scarce., Objective: To explore the links of CAIDE score to cerebrospinal fluid (CSF) biomarkers of AD as well as to cognitive performance., Methods: In the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, we recruited 600 cognitively normal participants. Correlations between the CAIDE score and CSF biomarkers of AD as well as cognitive performance were probed through multiple linear regression models. Whether the correlation between CAIDE score and cognitive performance was mediated by AD pathology was researched by means of mediation analyses., Results: Linear regression analyses illustrated that CAIDE score was positively associated with tau-related biomarkers, including pTau (p < 0.001), tTau (p < 0.001), as well as tTau/Aβ42 (p = 0.008), while it was in negative association with cognitive scores, consisting of MMSE score (p < 0.001) as well as MoCA score (p < 0.001). The correlation from CAIDE score to cognitive scores was in part mediated by tau pathology, with a mediation rate varying from 3.2% to 13.2%., Conclusions: A higher CAIDE score, as demonstrated in our study, was linked to more severe tau pathology and poorer cognitive performance, and tau pathology mediated the link of CAIDE score to cognitive performance. Increased dementia risk will lead to cognitive decline through aggravating neurodegeneration.

Liver function has been suggested as a possible factor in the progression of Alzheimer's disease (AD) development. However, the association between liver function and cerebrospinal fluid (CSF) levels of AD biomarkers remains unclear. In this study, we analyzed the data from 1687 adults without dementia from the Chinese Alzheimer's Biomarker and LifestylE study to investigate differences in liver function between pathological and clinical AD groups, as defined by the 2018 National Institute on Aging-Alzheimer's Association Research Framework. We also examined the linear relationship between liver function, CSF AD biomarkers, and cognition using linear regression models. Furthermore, mediation analyses were applied to explore the potential mediation effects of AD pathological biomarkers on cognition. Our findings indicated that, with AD pathological and clinical progression, the concentrations of total protein (TP), globulin (GLO), and aspartate aminotransferase/alanine transaminase (ALT) increased, while albumin/globulin (A/G), adenosine deaminase, alpha-L-fucosidase, albumin, prealbumin, ALT, and glutamate dehydrogenase (GLDH) concentrations decreased. Furthermore, we also identified significant relationships between TP (β = -0.115, p FDR  < 0.001), GLO (β = -0.184, p FDR  < 0.001), and A/G (β = 0.182, p FDR  < 0.001) and CSF β-amyloid 1-42 (Aβ 1-42 ) (and its related CSF AD biomarkers). Moreover, after 10 000 bootstrapped iterations, we identified a potential mechanism by which TP and GLDH may affect cognition by mediating CSF AD biomarkers, with mediation effect sizes ranging from 3.91% to 16.44%. Overall, our results suggested that abnormal liver function might be involved in the clinical and pathological progression of AD. Amyloid and tau pathologies also might partially mediate the relationship between liver function and cognition. Future research is needed to fully understand the underlying mechanisms and causality to develop an approach to AD prevention and treatment approach., (© 2023 International Society for Neurochemistry.)

Introduction: To examine the extent to which positron emission tomography (PET)-, cerebrospinal fluid (CSF)-, and plasma-related amyloid-β/tau/neurodegeneration (A/T/N) biomarkers are associated with Alzheimer's disease (AD) neuropathology at autopsy., Methods: A total of 100 participants who respectively underwent antemortem biomarker measurements and postmortem neuropathology were included in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We examined the associations of PET-, CSF-, and plasma-related A/T/N biomarkers in combinations or alone with AD neuropathological changes (ADNC)., Results: PET- and CSF-related A/T/N biomarkers in combination showed high concordance with the ADNC stage and alone showed high accuracy in discriminating autopsy-confirmed AD. However, the plasma-related A/T/N biomarkers alone showed better discriminative performance only when combined with apolipoprotein E (APO)E ε4 genotype., Discussion: This study supports that PET- and CSF-related A/T/N profiles can be used to predict accurately the stages of AD neuropathology. For diagnostic settings, PET-, CSF-, and plasma-related A/T/N biomarkers are all useful diagnostic tools to detect the presence of AD neuropathology., Highlights: PET- and CSF-related A/T/N biomarkers in combination can accurately predict the specific stages of AD neuropathology. PET- and CSF-related A/T/N biomarkers alone may serve as a precise diagnostic tool for detecting AD neuropathology at autopsy. Plasma-related A/T/N biomarkers may need combined risk factors when used as a diagnostic tool. Aβ PET and CSF p-tau181/Aβ42 were most consistent with Aβ pathology, while tau PET and CSF p-tau181/Aβ42 were most consistent with tau pathology., (© 2023 the Alzheimer's Association.)

Introduction: This study aimed to assess whether biomarkers related to amyloid, tau, and neurodegeneration can accurately predict Alzheimer's disease (AD) neuropathology at autopsy in early and late clinical stages., Methods: We included 100 participants who had ante mortem biomarker measurements and underwent post mortem neuropathological examination. Based on ante mortem clinical diagnosis, participants were divided into non-dementia and dementia, as early or late clinical stages., Results: Amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) amyloid beta (Aβ)42/phosphorylated tau (p-tau)181 showed excellent performance in differentiating autopsy-confirmed AD and predicting the risk of neuropathological changes in early and late clinical stages. However, CSF Aβ42 performed better in the early clinical stage, while CSF p-tau181, CSF t-tau, and plasma p-tau181 performed better in the late clinical stage., Discussion: Our findings provide important clinical information that, if using PET, CSF, and plasma biomarkers to detect AD pathology, researchers must consider their differential performances at different clinical stages of AD., Highlights: Amyloid PET and CSF Aβ42/p-tau181 were the most promising candidate biomarkers for predicting AD pathology. CSF Aβ42 can serve as a candidate predictive biomarker in the early clinical stage of AD. CSF p-tau181, CSF t-tau, and plasma p-tau181 can serve as candidate predictive biomarkers in the late clinical stage of AD. Combining APOE ε4 genotypes can significantly improve the predictive accuracy of AD-related biomarkers for AD pathology., (© 2023 the Alzheimer's Association.)

In order to comprehensively evaluate the quality of Viticis Fructus, this study established HPLC fingerprints and evaluated the quality of 24 batches of Viticis Fructus samples from different species by similarity evaluation and multivariate statistical analysis(PCA, HCA, PLS-DA). On this basis, an HPLC method was established to compare the content differences of the main components, including casticin, agnuside, homoorientin, and p-hydroxybenzoic acid. The analysis was performed on the chromatographic column(Waters Symmetry C&#95;(18)) with a gradient mobile phase of acetonitrile(A)-0.05% phosphoric acid solution(B) at the flow rate of 1 mL·min~(-1) and detection wavelength of 258 nm. The column temperature was 30 ℃ and the injection volume was 10 μL. The HPLC fingerprint of 24 batches of Viticis Fructus samples was established with 21 common peaks, and nine peaks were identified. Similarity analysis was carried out based on chromatographic data of 24 batches of chromatographic data of Viticis Fructus, and the results showed that except for DYMJ-16, the similarity of Vitex trifolia var. simplicifolia was ≥0.900, while that of V. trifolia was ≤0.864. In addition, the similarity analysis of two different species showed that the similarity of 16 batches of V. trifolia var. simplicifolia was 0.894-0.997 and that of the eight batches of V. trifolia was between 0.990 and 0.997. The results showed that the similarity of fingerprints of these two species was different, but the similarity between the same species was good. The results of the three multivariate statistical analyses were consistent, which could distinguish the two different species. The VIP analysis results of PLS-DA showed that casticin and agnuside contributed the most to the distinction. The content determination results showed that there was no significant difference in the content of homoorientin and p-hydroxybenzoic acid in Viticis Fructus from different species, but the content of casticin and agnuside was significantly different in different species(P&lt;0.01). The content of casticin was higher in V. trifolia var. simplicifolia, while agnuside was higher in V. trifolia. The findings of this study show that there are differences in fingerprint similarity and component content of Viticis Fructus from different species, which can provide references for the in-depth study of the quality and clinical application of Viticis Fructus.

Background: Previous studies have suggested a correlation between elevated levels of β 2 -microglobulin (B2M) and cognitive impairment. However, the existing evidence is insufficient to establish a conclusive relationship. This study aims to analyze the link of plasma B2M to cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers and cognition., Methods: To track the dynamics of plasma B2M in preclinical AD, 846 cognitively healthy individuals in the Chinese Alzheimer's Biomarker and LifestylE (CABLE) cohort were divided into four groups (suspected non-AD pathology [SNAP], 2, 1, 0) according to the NIA-AA criteria. Multiple linear regression models were employed to examine the plasma B2M's relationship with cognitive and CSF AD biomarkers. Causal mediation analysis was conducted through 10,000 bootstrapped iterations to explore the mediating effect of AD pathology on cognition., Results: We found that the levels of plasma B2M were increased in stages 1 (P = 0.0007) and 2 (P < 0.0001), in contrast to stage 0. In total participants, higher levels of B2M were associated with worse cognitive performance (P = 0.006 for MMSE; P = 0.012 for MoCA). Moreover, a higher level of B2M was associated with decreases in Aβ 1-42 (P < 0.001) and Aβ 1-42 /Aβ 1-40 (P = 0.015) as well as increases in T-tau/Aβ 1-42 (P < 0.001) and P-tau/Aβ 1-42 (P < 0.001). The subgroup analysis found B2M correlated with Aβ 1-42 in non-APOE ε4 individuals (P < 0.001) but not in APOE ε4 carriers. Additionally, the link between B2M and cognition was partially mediated by Aβ pathology (percentage: 8.6 to 19.3%), whereas tau pathology did not mediate this effect., Conclusions: This study demonstrated the association of plasma B2M with CSF AD biomarkers as well as a possible important role of Aβ pathology in the association between B2M and cognitive impairment, particularly in cognitively normal individuals. The results indicated that B2M could be a potential biomarker for preclinical AD and might have varied functions throughout various stages of preclinical AD progression., (© 2023. The Author(s).)

Background: Titanium dioxide (TiO 2 ) nanotubes arrays have shown tremendous application foreground due to their unique characters of structure and performance. However, the single bio-function is still the limit on cardiovascular biomaterials., Methods: The loadability function provides the possibility for the TiO 2 nanotubes arrays to realize composite multifunction. The copper can catalyze the release of nitric oxide to promote the proliferation of endothelium cells and improve the anticoagulant. Also, zinc can adjust the inflammatory responses to improve anti-inflammation., Results: In this patent work, we co-doped the copper and zinc onto TiO 2 nanotubes arrays to estimate the hemocompatibility, cytocompatibility and responses of inflammation. The results showed that copper and zinc could introduce better multi-biofunctions to the TiO 2 nanotubes arrays for the application in cardiovascular biomaterials., Conclusion: In summary, the NTs@Cu/Zn sample as a new composite material in this study had significant biocompatibility in vascular implantation and can be used as a potential material for polymer- free drug-eluting stents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To investigate the clinicopathological characteristics, immunophenotype, molecular characteristics, differential diagnosis, clinical treatment and prognosis of mixed carcinoma of cervix with adenoid cystic pattern. Methods: Three cases of mixed cervical carcinoma with adenoid cystic pattern were collected at the Affiliated Hospital of Xuzhou University Medical School from 2018 to 2021.The clinicopathological characteristics were analyzed, immunohistochemistry (IHC) and in situ hybridization (ISH) were performed. The related literature was reviewed. Results: The three patients were postmenopausal women with a median age of 74.7 years. The clinical symptom was vaginal bleeding without obvious causes. One case was an endophytic tumor, and the others were exophytic. The median diameter of the three cases was 3.3 cm. Two patients underwent hysterectomy, the tumors infiltrated the external 1/3 and middle 1/3 of the cervix respectively. All the lymph nodes were negative. One patient had a previous biopsy. Microscopically, all three tumors were characterized by a cribriform structure, which were filled with basophilic myxoid substance and surrounded by tubules lined by two layers of cells. The tumor cells had scanty cytoplasm and showed the characteristics of cervical basal-like cells. All three cases were accompanied by high-grade squamous intraepithelial lesions and squamous cell carcinoma, and one also showed a non-specific spindle cell sarcomatoid component. Within the double-layered epithelial structure, the outer epithelium was positive for p63, CD117, p16 INK4a (clone E6H4) and MYB protein and negative for S-100 by IHC. The combined positive score of PD-L1 (clone 22C3) was less than 1 in all three cases. Human papillomavirus (HPV) types 16 and 18 were detected in one patient preoperatively, while high-risk HPV were positive in the other two patients by RNAscope ISH postoperatively. None of the three cases showed MYB gene rearrangement by FISH. The mean follow-up time was 23.3 months (36, 28 and 6 months, respectively). Two patients underwent hysterectomy and radiotherapy survived without disease. One patient survived with tumor just by radiotherapy and drug therapy. Conclusions: Mixed cervical carcinoma with adenoid cystic pattern is extremely rare. It is a high-grade malignancy with poor prognosis. The tumor is associated with high-risk HPV infection, without MYB gene rearrangement, and with low PD-L1 immunoreactivity. Radical surgery combined with radiotherapy and chemotherapy is the mainstay of treatment at present.

Neurodegenerative diseases (NDDs) are chronic neurological disorders associated with cognitive or motor dysfunction. As a common spice, Zingiber officinale Roscoe has been used as a medicine to treat a variety of NDDs. However, at the molecular level, the mechanisms of Z. officinale in treating of NDDs have not been deeply investigated. In this study, network pharmacology method, molecular docking, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to predict the mechanisms of Z. officinale in the treatment of NDDs. After a series of biological information analyses, five core targets were obtained, including heme oxygenase 1 (HMOX1), acetylcholinesterase (AChE), nitric oxide synthase (NOS), catechol-O-methyl-transferase (COMT), and metabotropic glutamate receptor 5 (mGluR5). Compounds 75, 68, 46, 67, 69, 49, 66, 50, 34, and 64 were identified as the main components of Z. officinale in the treatment of NDDs. The crucial pathways mainly include neuroactive ligand-receptor signaling pathways, cyclic adenosine monophosphate signaling pathways, dopamine synaptic signaling pathways, and so on. Besides, in vitro experiments by AChE inhibitory activities assay and neuroprotective activities against H 2 O 2 -induced injury in human neuroblastoma SH-SY5Y cells validated the reliability of the results of network analysis. PRACTICAL APPLICATIONS: Zingiber officinale Roscoe is widely used as a traditional spice and herbal medicine. It contains a number of active ingredients, which have shown activities on anti-neurodegenerative diseases (NDDs). In this paper, the potential mechanism of Z. officinale in the treatment of NDDs is explored through network pharmacology, and it was verified by in vitro experiments. The mechanism was not only clarified at the system level but also proved to be effective at the biological level. The results can be used as a reference for Z. officinale in the treating of NDDs., (© 2022 Wiley Periodicals LLC.)

Background: Postoperative brain edema is a common complication in patients with high-grade glioma after craniotomy. Both Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are applied to diagnose brain edema. Usually, MRI is considered to be better than CT for identifying brain edema. However, MRI is not generally applied in diagnosing acute cerebral edema in the early postoperative stage. Whether CT is reliable in detecting postoperative brain edema in the early stage is unknown., Objective: This study aimed at investigating the agreement and correlation between CT and MRI for measuring early postoperative brain edema., Methods: Patients with high-grade glioma who underwent craniotomy in the Beijing Tiantan hospital from January 2017 to October 2018 were retrospectively analyzed. The region of interest and operative cavity were manually outlined, and the volume of postoperative brain edema was measured on CT and MRI. Pearson correlation testing and the Intraclass Correlation Coefficient (ICC) were used to evaluate the association and agreement between CT and MRI for detecting the volume of postoperative brain edema., Results: Twenty patients were included in this study. The interrater agreement was perfect for detecting brain edema (CT: κ=1, ICC=0.977, P<0.001; MRI: κ=0.866, ICC=0.963, P<0.001). A significant positive correlation and excellent consistency between CT and MRI were found for measuring the volume of brain edema (rater 1: r=0.97, ICC=0.934, P<0.001; rater 2: r=0.97, ICC=0.957, P<0.001)., Conclusion: Substantial comparability between CT and MRI is demonstrated for detecting postoperative brain edema. It is reliable to use CT for measuring brain edema volume in the early stage after surgery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The relationship between serum uric acid (UA) and Alzheimer's disease (AD) risk still remained ambiguous despite extensive attempts., Objective: Via the two-sample Mendelian randomization (MR) design, we aimed to examine the bidirectional causal relationships of serum UA, gout, and the risk of AD., Methods: Genetic variants of UA, gout, and AD were extracted from published genome-wide association summary statistics. The inverse-variance weighted (IVW, the primary method), and several sensitivity methods (MR-Egger, weighted median, and weighted mode) were used to calculate the effect estimates. Egger regression, MR-PRESSO and leave-one-SNP-out analysis were performed to identify potential violations., Results: Genetic proxies for serum UA concentration [odds ratio (ORIVW) = 1.09, 95% confidence interval (CI) = 1.01-1.19, p = 0.031] were related with an increased risk of AD using 25 single nucleotide polymorphisms (SNPs). This causal effect was confirmed by sensitivity analyses including MR-Egger (1.22, 1.06-1.42, p = 0.014), weighted median (1.18, 1.05-1.33, p = 0.006), and weighted mode (1.20, 1.07-1.35, p = 0.005) methods. No evidence of notable directional pleiotropy and heterogeneity were identified (p &gt; 0.05). Three SNPs (rs2078267, rs2231142, and rs11722228) significantly drove the observed causal effects. Supportive causal effect of genetically determined gout on AD risk was demonstrated using two SNPs (ORIVW = 1.05, 95% CI = 1.00-1.11, p = 0.057). No reverse causal effects of AD on serum UA levels and gout risk were found., Conclusion: The findings revealed a causal relationship between elevated serum UA level and AD risk. However, further research is still warranted to investigate whether serum UA could be a reliable biomarker and therapeutic target for AD.

Objective: To summarize the clinical characteristics and laboratory diagnostic methods of infant botulism caused by Clostridium botulinum type B. Methods: Clinical data of 3 infants with type B botulism who were admitted to Children's Hospital Affiliated to Capital Institute of Pediatrics from May to November 2018 were retrospectively analyzed. Botulinum toxin was detected in fecal samples or fecal enrichment solution of the patients, and Clostridium botulinum was cultured and isolated from fecal samples. Results: The age of onset of the patients (two boys and one girl) was 3, 3 and 8 months old, respectively. Two cases had the onset in May and one case had the onset in November. There were two cases with mixed feeding and one case with breast feeding. One case's family members engaged in meat processing. All of them were previously healthy. All the children presented with acute flaccid paralysis, cranial nerve involvement and difficult defecation. Two cases had secondary urinary tract infection. Electromyograms of two cases showed that action potential amplitude of the motor nerve were lower than those of their peers. After treatments including intravenous human immunoglobulin, respiratory tract management, urethral catheterization, nasal feeding, etc., three cases recovered completely 2 to 4 months later. Type B botulinum toxin was detected in the fecal diluent of one patient, and the TPGYT enrichment solution and cooked meet medium of the feces of 3 patients, respectively. Clostridium botulinum B was identified from the feces of 3 infants after culture, isolation and purification. Conclusions: Combined with typical clinical manifestations including acute flaccid paralysis, cranial nerve involvement symptoms and difficult defecation examination, infant botulism can be clinically diagnosed. The detection of fecal botulinum toxin and the culture and isolation of Clostridium botulinum are helpful for the diagnosis.

Neogenkwanine I ( 1 ), a new daphnane-type diterpene with 4,7-ether group, along with four known ones ( 2 - 5 ), were isolated from Daphne genkwa . The structure including absolute configurations of 1 was established on the basis of NMR, 13 C-NMR and ECD calculations and CD exciton chirality analysis. 13 C-NMR and ECD calculations of daphnane-type diterpenes were reported here for the first time. All of the diterpenes were screened for their cytotoxic activities against MCF-7 and Hep3B cell lines. The cytotoxicity structure- activity relationship of compounds was illustrated with the absence of ortho-ester group of daphnane-type diterpenes.

Recent genome-wide association studies (GWAS) indicated that polymorphisms in ADAMTS7 were associated with artery disease caused by atherosclerosis. However, the correlation between the ADAMTS7 polymorphism and plaque stability remains unclear. The objective of this study was to evaluate the association between 2 ADAMTS7 variants rs3825807 and rs7173743 and ischemic stroke or atherosclerotic plaque vulnerability.This research is an observational study. Patients with ischemic stroke and normal control individuals admitted to Beijing Tiantan Hospital from May 2014 to October 2017 were enrolled. High-resolution magnetic resonance imaging was used to distinguish vulnerable and stable carotid plaques. The ADAMTS7 SNPs were genotyped using TaqMan assays on real-time PCR system. The multivariate logistic regression analyses were used to adjust for multiple risk factors between groups.Three hundred twenty-six patients with ischemic stroke (189 patients with vulnerable plaque and 81 patients with stable plaque) and 432 normal controls were included. ADAMTS7 polymorphisms of both rs7173743 and rs3825807 were associated with carotid plaque vulnerability but not the prevalence of ischemic stroke. The T/T genotype of rs7173743 [odds ratio (OR) = 1.885, 95% confidence interval (CI) = 1.067-3.328, P = .028] and A/A genotype of rs3825807 (OR = 2.146, 95% CI = 1.163-3.961, P = .013) were considered as risk genotypes for vulnerable plaque susceptibility.In conclusion, ADAMTS7 variants rs3825807 and rs7173743 are associated with the risk for carotid plaque vulnerability.

Neurodegenerative diseases (NDDs) are characterized by progressive and irreversible, is a kind of complex illnesses, and the long-term therapy which is frequently associated with adverse side effects. Medicago sativa L., widely consumed as a vegetable, has the effects of improving memory and relieving central nervous system diseases. However, there are less studies on its specific mechanism for NDDs. In this investigation, we applied a method of network pharmacology, which combined molecular docking and network analysis to decipher the mechanisms of M. sativa in NDDs. The pharmacological system generated 55 triterpene saponins from M. sativa, and predicted 27 potential targets with 100 pathways in the treatment of NDDs. As a result, 13 compounds, 10 target proteins, and 6 signaling pathways were found to play important roles in the treatment of NDDs. In addition, in vitro experiments of isolates confirmed activities for NDDs, which were consistent with the results of network pharmacology prediction. PRACTICAL APPLICATIONS: Medicago sativa L. has been widely consumed as a vegetable, which possesses many nutritional components. As a functional food stuff, M. sativa can improve human health, such as memory improving activities, relieving central nervous system diseases, immunomodulatory, antioxidant, anticancer, and anti-inflammatory. In this article, the mechanism of triterpene saponins from M. sativa against NDDs was successfully predicted by network pharmacology method. The results will serve as a reference of M. sativa against NDDs., (© 2019 Wiley Periodicals, Inc.)

Purpose: The purpose of this study was to investigate whether alterations of regional neural function in children with diffuse intrinsic pontine glioma (DIPG) had manifested deficit in behavioral inhibition using resting-state functional MRI (rs-fMRI)., Methods: There were 17 participants with DIPG who took part in the study. Eight children were with deficit in behavioral inhibition, whereas the other 9 children did not obtain deficit in behavioral inhibition. Five healthy children with age, sex, and education matched to the study group also participated as the control group. These 3 groups underwent rs-fMRI, and the results were then converted to amplitude of low-frequency fluctuation (ALFF) data. Amplitude of low-frequency fluctuation data were further analyzed by single-factor analysis of variance comparing among 3 groups based on the whole brain levels. Amplitude of low-frequency fluctuation results were subjected to t test of voxel-wised comparison to derive the rs-fMRI brain function differences between the 2 DIPG groups. The Pearson correlation between ALFF values of abnormal regions found in 3 groups and the scores obtained according to the Child Behavior Checklist were analyzed., Results: The 3 groups had shown significant differences in terms of the ALFF results, with the ALFF increased in several brain regions (P < 0.05, corrected with AlphaSim, clusters >59 voxels), which include left supramarginal gyrus, left dorsolateral superior frontal gyrus, right precentral gyrus, and right middle frontal gyrus. Participants with deficit in behavioral inhibition had shown significant differences (ALFF decreased) in several brain regions, including left dorsolateral superior frontal gyrus and right fusiform gyrus (P < 0.05, corrected with AlphaSim, clusters >123 voxels), whereas other brain regions had shown ALFF increased, including left supramarginal gyrus, left middle frontal gyrus, and right medial superior frontal gyrus (P < 0.05, corrected with AlphaSim, clusters >123 voxels). There was no significant correlation between ALFF values and Child Behavior Checklist scores (P > 0.05)., Conclusions: These findings of focal spontaneous hyperfunction and hypofunction, which correlate with deficit in behavioral inhibition processing, and the abnormal brain regions are considered to be inefficient (in regions of the brain that may relate to compensatory brain and behavioral functioning, and it may be that the brain region needs to exert extra energy to perform a task to the same degree as the control group) or inability (inability in a certain region, or underpowered), pointing to a pathophysiologic process in executive dysfunction.

Three new withanolides (1-3), named as daturanolide A-C, along with six known withanolides (4-9) were isolated from the flowers of Datura metel L. Their structures with absolute configurations were elucidated by a series of spectroscopic methods, electronic circular dichroism (ECD) analyses, and X-ray crystallography. All the isolates were evaluated for cytotoxicity against five human cancer cell lines (HCT116, U87-MG, NCI-H460, BGC823, and HepG2), and 6 exhibited marked cytotoxicity., (© 2019 Wiley-VHCA AG, Zurich, Switzerland.)

Medicago sativa L. is a forage legume plant widely distributed in all continents. Six new triterpenoid saponins, Medicagosides A-F (1-6) and five known ones (7-11) were isolated from M. sativa. Their structures were determined via HRESIMS, 1D and 2D NMR analysis. Biologically, all the isolates displayed neuroprotective activities against H 2 O 2 -induced damage in SH-SY5Y cells. Among them, compounds 1, 3-5 and 10 exhibited striking neuroprotective activities at 100 μM, restoring cell viability range from 79.66% to 89.03%, relative to 79.46% (100 μM) of Trolox used as the positive control., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Five novel and rare cadinane-type sesquiterpene glycosides, cornucadinoside A-E (1-5) were isolated from water extract of the fruit of Cornus officinalis Sieb. et Zuuc.. The new chemical structures, together with their absolute configurations, were elucidated on the basis of extensive spectroscopic analysis, including a comparison of their experimental and calculated electronic circular dichroism (ECD) spectra. Their structures, which possess a naphthalene skeleton, are the first report on the occurrence of cadinane sesquiterpene glycosides in Cornus. Additionally, all the compounds exhibited marked α-glucosidase inhibitory activity except for 3in vitro., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: H3K27M is the most frequent mutation in brainstem gliomas (BSGs), and it has great significance in the differential diagnosis, prognostic prediction and treatment strategy selection of BSGs. There has been a lack of reliable noninvasive methods capable of accurately predicting H3K27M mutations in BSGs., Methods: A total of 151 patients with newly diagnosed BSGs were included in this retrospective study. The H3K27M mutation status was obtained by whole-exome, whole-genome or Sanger's sequencing. A total of 1697 features, including 6 clinical parameters and 1691 imaging features, were extracted from pre- and post-contrast T1-weighted and T2-weighted images. Using a random forest algorithm, 36 selected MR image features were integrated with 3 selected clinical features to generate a model that was predictive of H3K27M mutations. Additionally, a simplified prediction model comprising the Karnofsky Performance Status (KPS) at diagnosis, symptom duration at diagnosis and edge sharpness on T2 was established for practical clinical utility using the least squares estimation method., Results: H3K27M mutation was an independent prognostic factor that conferred a worse prognosis (p = 0.01, hazard ratio = 3.0, 95% confidence interval [CI], 1.57-5.74). The machine learning-based model achieved an accuracy of 84.44% (area under the curve [AUC] = 0.8298) in the test cohort. The simplified model achieved an AUC of 0.7839 in the test cohort., Conclusions: Using conventional MRI and clinical features, we established a machine learning-based model with high accuracy and a simplified model with improved clinical utility to predict H3K27M mutations in BSGs., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The use of thrombolysis in acute ischemic stroke is restricted to a small proportion of patients because of the rigid 4·5-h window. With advanced imaging-based patient selection strategy, rescuing penumbra is critical to improving clinical outcomes. In this study, we included 155 acute ischemic stroke patients (84 patients in training dataset, age from 43 to 80, 59 males; 71 patients in validation dataset, age from 36 to 80, 45 males) who underwent MR scan within the first 9-h after onset, from 7 independent centers. Based on the mismatch concept, penumbra and core area were identified and quantitatively analyzed. Moreover, predictive models were developed and validated to provide an approach for identifying patients who may benefit from thrombolytic therapy. Predictive models were constructed, and corresponding areas under the curve (AUC) were calculated to explore their performances in predicting clinical outcomes. Additionally, the models were validated using an independent dataset both on Day-7 and Day-90. Significant correlations were detected between the mismatch ratio and clinical assessments in both the training and validation datasets. Treatment option, baseline systolic blood pressure, National Institutes of Health Stroke Scale score, mismatch ratio, and three regional radiological parameters were selected as biomarkers in the combined model to predict clinical outcomes of acute ischemic stroke patients. With the external validation, this predictive model reached AUCs of 0·863 as short-term validation and 0·778 as long-term validation. This model has the potential to provide quantitative biomarkers that aid patient selection for thrombolysis either within or beyond the current time window., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC), the most common type of liver cancer, has high morbidity and mortality rates, and its prognosis is poor. The treatment options of HCC are limited by the lack of effective chemotherapy. Therefore, looking for effective drugs with little toxicity is very urgent. The aim of this study was to search for small molecule targeting on liver cancer from Juglans mandshurica, which has been used to treat cancers for a long time in China. Under the guide of anti-hepatoma activity, a new coumarin (1), together with eight reported analogs (2‒9), was isolated from the 75% EtOH extract. The structures of these compounds were determined by 1D and 2D NMR experiments. The absolute configuration of 1 was established by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. The in vitro cytotoxicity experiments on two liver cancer cell lines (HepG2 and Hep3B) showed that compounds 2 and 5 had moderate antitumor activities on both cell lines. And further studies of antitumor mechanisms by the observation of morphological changes and Western blot analyses exhibited that induction of apoptosis might be a possible way that inhibited cell growth.

Objective: To evaluate the efficacy of pleural abrasion in treatment of spontaneous pneumothorax with video-assisted thoracic surgery (VATS) for bullae resection. Methods: The clinical data of 158 patients with initial spontaneous pneumothorax who underwent video-assisted thoracic wedge resections with or without pleural abrasion in Henan Provincial People's Hospital from June 2010 to June 2015 were retrospectively analyzed. The patients were assigned to two equal groups according to whether pleural abrasion was applied or not: experimental group (with pleural abrasion) and control group (without pleural abrasion); and there were 79 patients in each group.There were 62 males and 17 females aged 15-60 years (mean age 34 years) in pleural abrasion group. And there were 70 males and 9 females aged 18-60 years (mean age 38 years) in non-pleural abrasion group.After surgery, all patients were evaluated for postoperative pain, chest tube removal time, hospital stay and other complications.Independent samples t test was used to compare the data between groups. Results: Surgeries for 158 patients were performed successfully.No mortality occurred.There was no conversion to thoracotomy.Postoperative pain, operation time, intraoperative blood loss, chest tube removal time, pleural canals flowand average hospital stay in non-pleural abrasion group was significantly lower for 4.4, 19 minutes, 10 ml, 21 hours, 87 ml and 1.4 days respectively when compared with those in pleural abrasion group ( t =32.478, 7.140, 11.093, 7.288, 10.246, 8.070, all P <0.05). There was no missing case with a follow-up of 30 months.No complications, such as pneumothorax, was observed. Conclusions: Postoperative pain, chest tube removal time and hospital stay in non-pleural abrasion group are all lower than those in pleural abrasion group.And there is no significant difference in the recurrence of pneumothorax between the two groups after VATS bullae resection.

Background: Functional magnetic resonance imaging (fMRI) mapping can present the activated cortical area during movement, while little is known about precise location in facial and tongue movements., Objective: To investigate the representation of facial and tongue movements by task fMRI., Methods: Twenty right-handed healthy subjects were underwent block design task fMRI examination. Task movements included lip pursing, cheek bulging, grinning and vertical tongue excursion. Statistical parametric mapping (SPM8) was applied to analysis the data., Results: One-sample t-test was used to calculate the common activation area between facial and tongue movements. Also, paired t-test was used to test for areas of over- or underactivation in tongue movement compared with each group of facial movements., Conclusions: The common areas within facial and tongue movements suggested the similar motor circuits of activation in both movements. Prior activation in tongue movement was situated laterally and inferiorly in sensorimotor area relative to facial movements. Prior activation of tongue movement was investigated in left superior parietal lobe relative to lip pursing. Also, prior activation in bilateral cuneus lobe in grinning compared with tongue movement was detected., (© 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, and treatment options for HCC are limited. In addition, the discovery of new natural compounds with anti-hepatocarcinoma activity is attracting increasing attention. For this reason, phytochemical investigation of Croton crassifolius led to the isolation of 17 diterpenoids, including three new clerodane diterpenoids, named crassifolius A-C (1-3), along with 14 known ones (4-17). Their structures were established by 1D, 2D NMR, HR-ESI-MS, detailed calculated electronic circular dichroism (ECD) spectra and the assistance of quantum chemical predictions (QCP) of 13 C NMR chemical shifts. The cytotoxicities of all these compounds against human liver cancer lines (HepG2 and Hep3B) were determined. Among them, compound 1 exhibited good cytotoxicity with IC 50 value of 17.91μM against human liver tumor cells Hep3B. Following further studies of the anti-tumor mechanism of compound 1-induced cell growth inhibition, we found that compound 1 caused apoptotic cell death in Hep3B cells by detecting morphologic changes and Western blotting analysis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To compare the respective effects of propofol and emulsified isoflurane administered alone and in combination with dexmedetomidine on the quality of induction of anesthesia, physiological variables and recovery in dogs., Study Design: Prospective, randomized, experimental trial., Animals: Thirty-six adult mixed-breed dogs., Methods: Animals were randomly assigned to one of four induction protocols: propofol alone (group P); emulsified isoflurane alone (group EI); both propofol and dexmedetomidine (group PD), or both emulsified isoflurane and dexmedetomidine (group EID). Pulse rate (PR), respiratory rate (fR ), non-invasive arterial blood pressure and arterial blood gases were measured at baseline, before induction, immediately after intubation (time 0), and at 5 minute intervals until the dog began to swallow and the trachea was extubated. The quality of induction and recovery, and degree of ataxia were scored by a single investigator unaware of group assignment. The durations of anesthesia and recovery, and the incidence of adverse events were recorded., Results: There were no clinically significant differences among the groups in induction quality. Systolic arterial pressure was lower in EID compared with P at 5 minutes. PR and fR were lower in PD and EID compared with P after induction. The PaCO2 at 5 minutes was higher than at baseline in group P. Ataxia score was lower in EID than in P. Time from induction to extubation and time from extubation to sternal recumbency were lower in EID compared with PD., Conclusions and Clinical Relevance: There were no clinically significant differences among the groups in induction quality. In PD and EID, but not in P, PR and fR were decreased after induction. The EID combination resulted in smooth and rapid induction and recovery and thus may be useful clinically for induction of anesthesia., (© 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Patients suffering different intervals of facial nerve injury were investigated by functional magnetic resonance imaging to study changes in activation within cortex.Forty-five patients were divided into 3 groups based on intervals of facial nerve injury. Another 16 age and sex-matched healthy participants were included as a control group. Patients and healthy participants underwent task functional magnetic resonance imaging (eye blinking and lip pursing) examination.Functional reorganization after facial nerve injury is dynamic and time-dependent. Correlation between activation in sensorimotor area and intervals of facial nerve injury was significant, with a Pearson correlation coefficient of -0.951 (P < 0.001) in the left sensorimotor area and a Pearson correlation coefficient of 0.333 (P = 0.025) in the right sensorimotor area.Increased activation in integration areas, such as supramarginal gyrus and precunes lobe, could be detected in the early-middle stage of facial dysfunction compared with normal individuals. Decreased activation in sensorimotor area contralateral to facial nerve injury could be found in late stage of facial dysfunction compared with normal individuals. Dysfunction in the facial nerve has devastating effects on the activity of sensorimotor areas, whereas enhanced intensity in the sensorimotor area ipsilateral to the facial nerve injury in middle stage of facial dysfunction suggests the possible involvement of interhemispheric reorganization. Behavioral or brain stimulation technique treatment in this stage could be applied to alter reorganization within sensorimotor area in the rehabilitation of facial function, monitoring of therapeutic efficacy, and improvement in therapeutic intervention along the course of recovery.

Based on the fact that timosaponin A-III (TA-III) exhibits potent cytotoxic effects and has been considered as a potential anti-tumor agent, a range of novel sarsasapogenin derivatives 1, 2a-2g, 3, 4, 5, 6a-6g have been synthesized by a simple and facile synthetic route. The in vitro cytotoxic activity of these synthetic compounds has been evaluated against ten human cancer cell lines. The pharmacological results showed that most of the sarsasapogenin derivatives displayed excellent selective cytotoxicity toward the cancer cell lines. An amino group at C-3 or C-26 position of the sapogenin had a profound influence on the cytotoxic activity. In particular, compound 6c exhibited significantly inhibitory activity against A375-S2 (IC50=0.56μM) and HT1080 (IC50=0.72μM) cells. However, introducing a bromo or morpholinyl substituent at the C-3 and C-26 position of the sapogenin generally rendered it inactive against the human cancer cell lines. This research provides a theoretical reference for the exploration of new anti-tumor drugs., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Unlabelled: OBJECTIVE To explore the perihematomal perfusion typing and spot sign on computed tomography angiography (CTA) source images in order to assist in individualizing therapeutic decisions for patients with intracerebral hemorrhage by possibly forecasting perihematomal ischemia and hematoma enlargement. METHODS We examined 58 patients with spontaneous intracerebral hemorrhage by computed tomography perfusion and CTA within 6 hours after symptom onset. Hematoma volumes were determined from non-contrast CT images and compared between first and second CT images. The perfusion of hematoma region and perihematoma region was evaluated for presence or absence of the perihematomal penumbra. Three kinds of perihematoma perfusion typing were defined according to the perfusion of hematoma region and perihematoma region. CTA source images was reviewed to make sure presence or absence of the spot sign. RESULTS Finally, 53 patients (34 males, 19 females) were enrolled in our study according to exclusion criteria. Finally, 21 patients were classified into the normal group, 23 patients were classified into the mild group, and 9 patients were classified into the severe group. There were significant differences in hematoma size between the presence and absence of the perihematomal penumbra group (P<0.05). Thirteen (24.5%) patients presented with spot sign. Hematoma expansion occurred in 15 (28.3%) patients on follow-up. In which 12 patients were with spot sign. Sensitivity, specificity, positive predictive value, and negative predictive value for expansion were 80.0%, 97.4%, 92.3%, and 92.5%, respectively., Conclusion: In acute intracerebral hemorrhage patients, the perihematoma perfusion typing and CTA spot sign provide more radiological information that might assist in individualizing therapeutic decisions for patients by possibly forecasting perihematomal ischemia and hematoma enlargement.

Objectives: Exact characterization and localization of white matter lesions (WMLs) as they relate and contribute to vascular cognitive impairment is highly debated. The purpose of this study was to investigate the impact of WML on cognitive function by using a new anatomy-based classification method., Methods: We detected WML accurately by using a three-dimensional fluid-attenuated inversion recovery (3D FLAIR) imaging technique and subsequently segmented WMLs by using an anatomy-based method. Participants included 56 consecutive patients diagnosed with subcortical vascular cognitive impairment (SubVCI). The volume of WMLs in different anatomic regions was measured. The volume of the hippocampus, the corpus callosum (CC), any lacunar infarcts, total gray matter (GM), and total brain volumes were also calculated., Results: Hippocampal (P  =  0.005) as well as temporal WML volumes (P  =  0.039) were both independently associated with mini-mental state examination (MMSE) score. Only the parietal WML volume (P  =  0.000) was independently associated with Montreal Cognitive Assessment (MoCA) score. Frontal WMLs were independently correlated with executive function. Occipital WMLs were independently associated with visuospatial and recall function. Language impairment was independently correlated with both parietal GM and parietal WML volume. Functions related to orientation were independently associated with parietal WML volume., Discussion: The volume of WMLs in the temporal region as well as in the hippocampus were both independently associated with MMSE score. For the MoCA score, however, only parietal WML volumes were independently correlated. White matter lesions within different anatomic regions were separately correlated with different subdomains of cognitive function.

Two new alkaloids named (3R)-3,5-bis(3-methoxy-4-hydroxyphenyl)-2,3-dihydro-2(1H)-pyridinone (1) and 1,5-dimethyl-6-phenyl-1,2-dihydro-1,2,4-triazin-3(2H)-one (2), together with two known compounds (7'R)-N-feruloyl normetanephrine (3) and N-trans-feruloyl tyramine (4) were isolated from the air-dried aerial parts of Portulaca oleracea L. Their structures and configurations were elucidated by spectroscopic methods including 1D NMR, 2D NMR, and HR-MS techniques. In addition, compounds 1-4 were tested for in vitro cytotoxic activities against human lung (K562 and A549) and breast (MCF-7 and MDA-MB-435) cancer cell lines.