Development and validation of a predictive model for stroke associated pneumonia in patients after thrombectomy for acute ischemic stroke.

Objective: This study aims to identify the risk factors associated with stroke-associated pneumonia (SAP) in patients who have undergone thrombectomy for acute ischemic stroke and to develop a nomogram chart model for predicting the occurrence of pneumonia. Methods: Consecutive patients who underwent thrombectomy for acute ischemic stroke were enrolled from three hospitals at Taizhou Enze Medical Center. They were randomly divided into a training group and a validation group in a 7:3 ratio. The training group data was used to screen for effective predictive factors using LASSO regression. Multiple logistic regression was then conducted to determine the predictive factors and construct a nomogram chart. The model was evaluated using the validation group, analyzing its discrimination, calibration, and clinical decision curve. Finally, the newly constructed model was compared with the AIS-APS, A2DS2, ISAN, and PANTHERIS scores for acute ischemic stroke-associated pneumonia. Results: Out of 913 patients who underwent thrombectomy, 762 were included for analysis, consisting of 473 males and 289 females. The incidence rate of SAP was 45.8%. The new predictive model was constructed based on three main influencing factors: NIHSS ≥16, postoperative LMR, and difficulty swallowing. The model demonstrated good discrimination and calibration. When applying the nomogram chart to threshold probabilities between 7 and 90%, net returns were increased. Furthermore, the AUC was higher compared to other scoring systems. Conclusion: The constructed nomogram chart in this study outperformed the AIS-APS, A2DS2 score, ISAN score, and PANTHERIS score in predicting the risk of stroke-associated pneumonia in patients with acute ischemic stroke after thrombectomy. It can be utilized for clinical risk prediction of stroke-associated pneumonia in patients after thrombectomy for acute ischemic stroke.

Effects of different dietary fiber supplement strategies on incidence of acute gastrointestinal injury in ICU patients: A prospective observational study.

OBJECTIVE: This study aimed to explore the effects of dietary fiber (DF) supplement strategies on the incidence of acute gastrointestinal injury (AGI) in critically ill patients. DESIGN: A prospective observational study. SETTING: The study was conducted in the First Affiliated Hospital of Soochow University from April 2021 to March 2023. METHODS: Using a five-day dietary log counted the amount of DF supplement. The best fitting trajectories of DF supplement were determined based on the latent class trajectory modelling (LCTM). The data of AGI were evaluated on the day 5 (D5) and day 7 (D7) after intensive care unit admission. RESULTS: A total of 179 patients were included in the study. The LCTM yielded a four-trajectories of models, named; Sustained Low - Group, Slowly Rising - Group, Early Supplement & Slowly Rising - Group and Rapidly Rising - Group, respectively. The incidences of AGI on D5 and D7 were 51.4 % and 40.0 %, respectively. There was an increased risk in the grade of AGI in the Sustained Low - Group compared with the Rapidly Rising - Group on D5 [odds ratio (OR), 4.8; 95 % confidence interval (CI), 1.9-12.1] and D7 (OR, 12.0; 95 % CI, 3.9-37.0); and an increased risk in the Slowly Rising - Group on D5 (OR, 3.6; 95 % CI, 1.3-9.9). CONCLUSION: The supplement of DF in critically ill patients may be insufficient and the incidence of AGI is high. Sustained low and slow rising DF supplement may be associated with an increased risk in the AGI. IMPLICATIONS FOR CLINICAL PRACTICE: The clinical staff could focus on the supplementation of not only the three macronutrients, but also DF in critically ill patients.

Ozone, hydrogen peroxide, and peroxymonosulfate disinfection of MS2 coliphage in water.

The control of viruses in water is critical to preventing the spread of infectious viral diseases. Many oxidants can inactivate viruses, and this study aims to systematically compare the disinfection effects of ozone (O3), peroxymonosulfate (PMS), and hydrogen peroxide (H2O2) on MS2 coliphage. The effects of oxidant dose and contact time on disinfection were explored, as were the disinfection effects of three oxidizing agents in secondary effluent. The 4-log inactivation of MS2 coliphage required 0.05 mM O3, 0.5 mM PMS, or 25 mM H2O2 with a contact time of 30 min. All three oxidants achieved at least 4-log disinfection within 30 min, and O3 required only 0.5 min. In secondary effluent, all three oxidants also achieved 4-log inactivation of MS2 coliphage. Excitation-emission matrix (EEM) results indicate that all three oxidants removed dissolved organic matter synchronously and O3 oxidized dissolved organic matter more thoroughly while maintaining disinfection efficacy. Considering the criteria of oxidant dose, contact time, and disinfection efficacy in secondary effluent, O3 is the best choice for MS2 coliphage disinfection among the three oxidants.

Silencing of LINC00707 Alleviates Brain Injury by Targeting miR-30a-5p to Regulate Microglia Inflammation and Apoptosis.

The role of microglia in traumatic brain injury (TBI) has gained considerable attention. The present study aims to elucidate the potential mechanisms of Long intergenic non-protein coding RNA 707 (LINC00707) in TBI-induced microglia activation and inflammatory factor release. An in vivo model of rat TBI and in vitro microglia model was established using Controlled cortex injury (CCI) and lipopolysaccharide (LPS) stimulation. RT-qPCR to detect LINC00707 levels in rat cerebral cortex or cells. Modified Neurological Impairment Score (mNSS) and Morris Water Maze test was conducted to assess the neurological deficits and cognitive impairment. ELISA analysis of pro-inflammatory factors levels. CCK-8 and flow cytometry for cell viability and apoptosis levels. Dual-luciferase report and RIP assay to validate the targeting relationship between LINC00707 and miR-30a-5p. LINC00707 was elevated in the TBI rat cerebral cortex and LPS-induced microglia, while miR-30a-5p was noticeably decreased (P < 0.05). Increased mNSS, cognitive dysfunction, and brain edema in TBI rats were all prominently reversed by silencing of LINC00707, but this reversal was partially abrogated by decreasing miR-30a-5p (P < 0.05). Inhibition of LINC00707 suppressed the overproduction of inflammatory factors in TBI rats (P < 0.05). LPS decreased microglial cell viability, increased apoptosis, and promoted inflammatory overproduction than control, but the silencing of LINC00707 reversed its effect. Suppression of miR-30a-5p attenuated this reversal (P < 0.05). miR-30a-5p was the target miRNA of LINC00707. All in all, the results suggested that inhibiting LINC00707/miR-30a-5p axis could alleviate the progression of TBI by suppressing the inflammation and apoptosis of microglia cells.

Association between regular physical activity and biomarker changes in early Parkinson's disease patients.

INTRODUCTION: Physical activity benefits patients with Parkinson's disease (PD) and is assumed to possess disease-modifying potential. PD-related biomarkers, such as dopamine transporter (DAT) imaging and cerebrospinal fluid (CSF) α-synuclein (α-syn) and amyloid ß (Aß), correlate with disease severity and, to some extent, reflect disease progression and pathology. However, the association between regular physical activity and PD biomarker changes remains unknown. This study aimed to investigate the association between physical activity and longitudinal trajectories of PD biomarkers. METHODS: This retrospective study included 444 patients with a median follow-up time of 5 years from the Parkinson's Progression Markers Initiative cohort. Data collection included physical activity as scaled by the Physical Activity Scale for the Elderly questionnaire, dopamine transporter imaging, CSF assessment, and serum biomarkers. We analyzed the data using a linear mixed regression model. RESULTS: Regular physical activity was associated with a slower decline of DAT uptake in the caudate (ß = 0.063, p = 0.011) and the putamen (ß = 0.062, p = 0.023). No association was detected between regular physical activity and CSF, as well as serum biomarkers. CONCLUSION: Regular physical activity is associated with favorable PD biomarker progression, indicating a potential disease-modifying effect.

A Ratiometric SERS Probe for Imaging the Macrophage Phenotypes in Live Mice with Epilepsy and Brain Tumor.

Macrophage performs multiple functions such as pathogen phagocytosis, antigen presentation, and tissue remodeling by polarizing toward a spectrum of phenotypes. Dynamic imaging of macrophage phenotypes is critical for evaluating disease progression and the therapeutic response of drug candidates. However, current technologies cannot identify macrophage phenotypes in vivo. Herein, a surface-enhanced Raman scattering nanoprobe, AH1, which enables the accurate determination of physiological pH with high sensitivity and tissue penetration depth through ratiometric Raman signals is developed. Due to the phenotype-dependent metabolic reprogramming, AH1 can effectively identify macrophage subpopulations by measuring the acidity levels in phagosomes. After intravenous administration, AH1 not only visualizes the spatial distribution of macrophage phenotypes in brain tumors and epileptic regions of mouse models, but also reveals the repolarization of macrophages in brain lesions after drug intervention. This work provides a new tool for dynamically monitoring the disease-associated immune microenvironment and evaluating the efficacy of immune-therapeutics in vivo.

Association between regular physical activity and biomarker changes in early Parkinson's disease patients.

INTRODUCTION: Physical activity benefits patients with Parkinson's disease (PD) and is assumed to possess disease-modifying potential. PD-related biomarkers, such as dopamine transporter (DAT) imaging and cerebrospinal fluid (CSF) α-synuclein (α-syn) and amyloid ß (Aß), correlate with disease severity and, to some extent, reflect disease progression and pathology. However, the association between regular physical activity and PD biomarker changes remains unknown. This study aimed to investigate the association between physical activity and longitudinal trajectories of PD biomarkers. METHODS: This retrospective study included 444 patients with a median follow-up time of 5 years from the Parkinson's Progression Markers Initiative cohort. Data collection included physical activity as scaled by the Physical Activity Scale for the Elderly questionnaire, dopamine transporter imaging, CSF assessment, and serum biomarkers. We analyzed the data using a linear mixed regression model. RESULTS: Regular physical activity was associated with a slower decline of DAT uptake in the caudate (ß = 0.063, p = 0.011) and the putamen (ß = 0.062, p = 0.023). No association was detected between regular physical activity and CSF, as well as serum biomarkers. CONCLUSION: Regular physical activity is associated with favorable PD biomarker progression, indicating a potential disease-modifying effect.

The Association of Planetary Health Diet with the Risk of Type 2 Diabetes and Related Complications: A Systematic Review.

BACKGROUND: Nutritional interventions such as the planetary health diet, which the EAT-Lancet commission proposed, may be an effective strategy for reducing type 2 diabetes risks and its associated complications. The planetary health diet demonstrates the significant role of diet in associating human health with environmental sustainability and the significance of transforming food systems in order to ensure that the UN's Sustainable Development Goals and the Paris Agreement are achieved. Therefore, the aim of this review is to examine the association of the planetary health diet (PHD) with the risk of type 2 diabetes and its related complications. METHOD: The systematic review was conducted in line with established guidelines. The searches were carried out in health sciences research databases through EBSCOHost. The population, intervention, comparator and outcomes framework was used in order to define the research question and the search terms. The searches were carried out from the inception of the databases to 15 November 2022. Search terms including synonyms and medical subject headings were combined using Boolean operators (OR/AND). RESULTS: Seven studies were included in the review and four themes were identified, including incidence of diabetes; cardiovascular risk factors and other disease risks; indicators of obesity and indicators of environmental sustainability. Two studies examined the association between the PHD and the incidence of type 2 diabetes and found that high adherence to the reference diet (EAT-Lancet reference diet) was correlated with a lower incidence of type 2 diabetes. High adherence to the PHD was also associated with some cardiovascular risk factors and environmental sustainability. CONCLUSION: This systematic review has shown that high adherence to the PHD is associated with a reduced risk of type 2 diabetes and may be associated with a lower risk of subarachnoid stroke. In addition, an inverse relationship was found between adherence to the PHD and markers of obesity and environmental sustainability. Adherence to the reference diet was also associated with lower values of some markers of cardiovascular risk. More studies are needed to fully examine the relationship between the planetary health diet, type 2 diabetes and its related conditions.

Guiding Epilepsy Surgery with an LRP1-Targeted SPECT/SERRS Dual-Mode Imaging Probe.

Accurate identification of the resectable epileptic lesion is a precondition of operative intervention to drug-resistant epilepsy (DRE) patients. However, even when multiple diagnostic modalities are combined, epileptic foci cannot be accurately identified in ∼30% of DRE patients. Inflammation-associated low-density lipoprotein receptor-related protein-1 (LRP1) has been validated to be a surrogate target for imaging epileptic foci. Here, we reported an LRP1-targeted dual-mode probe that is capable of providing comprehensive epilepsy information preoperatively with SPECT imaging while intraoperatively delineating epileptic margins in a sensitive high-contrast manner with surface-enhanced resonance Raman scattering (SERRS) imaging. Notably, a novel and universal strategy for constructing self-assembled monolayer (SAM)-based Raman reporters was proposed for boosting the sensitivity, stability, reproducibility, and quantifiability of the SERRS signal. The probe showed high efficacy to penetrate the blood-brain barrier. SPECT imaging showed the probe could delineate the epileptic foci clearly with a high target-to-background ratio (4.11 ± 0.71, 2 h). Further, with the assistance of the probe, attenuated seizure frequency in the epileptic mouse models was achieved by using SPECT together with Raman images before and during operation, respectively. Overall, this work highlights a new strategy to develop a SPECT/SERRS dual-mode probe for comprehensive epilepsy surgery that can overcome the brain shift by the co-registration of preoperative SPECT and SERRS intraoperative images.

Gradual financial integration and macroeconomic fluctuations in emerging market economies: evidence from China.

This paper extends the conventional DSGE literature by developing a New Keynesian DSGE model featuring imperfect financial markets with various friction costs, which allows for the study of macroeconomic dynamics under different levels of financial integration. We conduct Bayesian estimation and draw implications on the macroeconomic effects of gradual financial integration using the Chinese economy as an example. We find that macroeconomic fluctuations vary with different levels of financial integration and the specific relationship depends on the nature of exogenous shocks. Variance decomposition analysis shows that as financial integration increases, the contribution of foreign exchange shocks declines while that of domestic shocks increases. We also find that there is a notable enhancement of welfare associated with improvement in financial integration, and the effectiveness of monetary policy in emerging market economies would be weakened as financial integration increases.

Recent advances in ATM inhibitors as potential therapeutic agents.

ATM, a member of the PIKK-like protein family, plays a central role in responding to DNA double-strand breaks and other lesions to protect the genome against DNA damage. Loss of ATM's kinase function has been shown to increase the sensitivity of most cells to ionizing radiation. Therefore, ATM is thought to be a promising target for chemotherapy as a radiotherapy sensitizer. The mechanism of ATM in cancer treatment and the development of its inhibitors have become research hotspots. Here we present an overview of research concerning ATM protein domains, functions and inhibitors, as well as perspectives and insights for future development of ATM-targeting agents.

Atroposelective Amination of Indoles via Chiral Center Induced Chiral Axis Formation.

The construction of an N-C chiral axis for N-aryl indole derivatives is meaningful as they widely exist in functionalized molecules. This work provides a novel method for this purpose via amination of amino acid derivatives at the C2 position of the indole and chiral center induced chiral axis formation. The protocol of this transformation is easily accessible, not requiring metal or an organic chiral catalyst, endowing this method with great potential in the construction of axis chiral N-aryl indoles.

The Effect of Prebiotics and Oral Anti-Diabetic Agents on Gut Microbiome in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials.

Background: Nutritional interventions such as the use of prebiotics can promote eubiosis of gut microbiome and maintain glucose homeostasis in patients with type 2 diabetes (T2D). However, it would appear that results of the effects of prebiotics on the community of microbes in the gut are not consistent. Aim: To examine the effect of prebiotics and oral antidiabetic agents on gut microbiome in patients with T2D. Methods: The PRISMA Extension Statement for Systematic Reviews and Network Meta-analyses was used to conduct this review. Searches were carried out in EMBASE, EBSCO-host databases, Google Scholar and the reference lists of articles for studies that are relevant to the research question, from database inception to 15 August 2022. The search strategy was based on PICOS framework. Network Meta-analysis which allows the estimation of relative treatment effects by combing both direct trial evidence (e.g., treatment A vs. treatment B) and indirect evidence was conducted. Furthermore, pairwise meta-analysis was also carried out to estimate effect sizes based on head-to-head comparisons of treatments and/or control conditions. Results: Findings of the Network meta-analysis revealed that prebiotics significantly reduced HbA1c compared with control and the SMD was −0.43 [95% CI, −0.77, −0.08; p = 0.02], whereas there was no significant difference (p > 0.05) between the other treatments and control. In addition, anti-diabetic agents including glipizide and metformin also reduced HbA1C, although these were not significantly different (p > 0.05) from control. While prebiotics promoted Bifidobacterium and Akkermansia, the improvements were not significantly different (p > 0.05) from control. On the other hand, metformin decreased the relative abundance of Bifidobacterium, but increased Lactobacillus and Akkermansia, although the differences were not significant (p > 0.05) compared with control. With respect to fasting blood glucose and BMI, the effects of prebiotics and oral antidiabetic agents did not differ significantly (p > 0.05) from controls. Conclusions: The findings of the systematic review and Network meta-analysis demonstrated prebiotics were significantly (p < 0.05) more effective in reducing HbA1c than control in patients with T2D. However, the effects of prebiotics and oral antidiabetic agents did not differ significantly (p > 0.05) from the controls in relation to fasting blood glucose, post-prandial blood glucose, body mass index and the genera of gut bacteria examined. More studies are required to fully investigate the effects of prebiotics and oral antidiabetic agents in patients with T2D

Association between Dietary Carbohydrate Intake and Control of Blood Pressure in Patients with Essential Hypertension.

BACKGROUND: Both high and low percentages of carbohydrate diets were associated with increased mortality and new-onset hypertension. However, few studies have aggregated to explore the association between carbohydrate intake and blood pressure (BP) control in patients with hypertension. This study aimed to explore the association between carbohydrate-to-energy proportion (CEP) and the rate of poorly controlled BP in patients with hypertension. METHODS: A cross-sectional survey was conducted in one comprehensive hospital and one community clinic in China. Dietary CEP was obtained through two-24 h dietary recalls. According to the quintiles of CEP, the participants were divided into Q1-Q5 groups. The average of two BP values was adopted as the final BP value, and poorly controlled BP was defined as systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥ 90 mmHg. RESULTS: A total of 459 hypertensive patients were recruited. In univariate analyses, CEP was associated with the control of SBP and DBP. After the covariates were adjusted for, fewer CEPs in Q1 (OR, 4.335; 95% CI, 1.663, 11.299) and Q2 (OR, 2.482; 95% CI, 1.234, 4.989) were significantly associated with higher rates of poor SBP control. CONCLUSIONS: A lower dietary CEP is a risk factor for SBP control, whereas an appropriate CEP of 56% to 66% is beneficial for BP control in patients with essential hypertension.

Comparing Long-Term Survival Outcomes for Muscle-Invasive Bladder Cancer Patients Who Underwent with Radical Cystectomy and Bladder-Sparing Trimodality Therapy: A Multicentre Cohort Analysis.

Background: Although radical cystectomy (RC) is the clinical practice guideline-recommended treatment of muscle-invasive bladder cancer (MIBC), bladder-sparing trimodality therapy (TMT) has emerged as a valid treatment option. Findings comparing the survival outcomes for MIBC patients who underwent RC and TMT are inconclusive. Objective: We designed a large hospital-based multicohort study to compare the effectiveness of TMT with RC. Methods: Information on deaths was jointly retrieved from EMR (electronic medical record), cause of death registry, and chronic disease surveillance as well as study-specific questionnaire. To avoid the systematical difference between patients who received two modalities, RC-MIBC cohort was propensity score-matched to TMT-MIBC cohort, and the Cox proportional hazard regression was used to calculate the overall survival (OS) and disease-specific survival (DSS). Results: There were 891 MIBC patients treated with RC and another 891 MIBC patients who underwent with TMT in the propensity score matching. Comparable effectiveness between two modalities was observed for DSS (HR, 1.20; 95% confidence interval (CI), 0.94 to 1.49) and OS (HR, 1.17; 95% CI, 0.91 to 1.43) according to multiple adjustment after a median follow-up of approximately 9.3 years. However, a relatively higher mortality rate around 5 years after TMT treatment was found compared to RC (HR, 1.26; 95% CI, 1.01 to 1.53). The respective 5-year OS rates were 69% and 73% for TMT cohort and RC cohort, respectively. Conclusions: Our findings supported that MIBC patients with TMT yielded survival outcomes comparable to MIBC patients who underwent RC overall. Treatment options should be suggested considering patients' age and willingness.

Inhibitors of cell cycle checkpoint target Wee1 kinase - a patent review (2003-2022).

INTRODUCTION: DNA damage repair in most malignancies with mutation of p53 is more dependent on the G2/M checkpoint. Wee1 kinase is a key regulator of the G2/M checkpoint. If Wee1 is inhibited, it results in cells with unrepaired DNA damage entering mitosis prematurely, leading to mitotic catastrophe and subsequent cell death via the apoptotic program. Therefore, inhibition of Wee1 kinase which overexpressed in several cancer cell lines has emerged as a promising therapy for cancer treatment. AREAS COVERED: This review summarizes for the first time the structures of small-molecule inhibitors of Wee1 reported in patents published from 2003 to 2022 and the recent clinical developments. It also provides perspectives on the challenges and the future directions. We used different methods to search different databases (PubMed, Reaxys, clinicaltrials.gov)for the literature we needed. EXPERT OPINION: Although the small-molecule inhibitors of Wee1, Adavosertib, and ZN-C3 have entered the clinical phase II, the clinical toxicity exhibited by Adavosertib remains the subject of greater concern. The use of Wee1 inhibitors as monotherapy or in combination therapy remains the main trend in Wee1 inhibitors at present.

RAPID Software to the Clinical Application Value of Acute Basilar Artery Occlusion with Endovascular Treatment.

OBJECTIVE: To investigate the clinical application value of RAPID software based on computed tomography perfusion imaging (CTP) in the endovascular treatment of acute basilar artery occlusion (BAO). MATERIALS AND METHODS: The data of patients with acute basilar artery occlusion who received endovascular treatment in Taizhou Hospital, Zhejiang Province, between January 2020 and April 2021 were retrospectively analysed. The patients were divided into a perfusion imaging and a no-perfusion imaging group based on whether the image analysis results were obtained by RAPID software. Age, preoperative National Institute of Health stroke scale (NIHSS) score, onset to puncture time (OPT), operation methods, good prognosis at 3 months after surgery (modified Rankin scale (mRS) score ≤3), symptomatic intracranial haemorrhage (sICH) and other clinical data were compared between the two groups. Multivariate logistic regression analysis was used to identify the independent factors affecting the prognosis of BAO patients. RESULTS: In total, 61 patients with acute BAO were included: 31 patients in the perfusion imaging group and 30 patients in the no-perfusion imaging group. There were no statistically significant differences between the two groups in age, NIHSS score or operation methods (all P >0.05). However, OPT and the good prognosis rate were significantly higher in the perfusion imaging group than in the no-perfusion imaging group (χ2=8.176, 5.003, P < 0.05). SICH was significantly lower in the perfusion imaging group than in the no-perfusion imaging group (χ2=5.628, P < 0.05). Logistic regression analysis showed that the image analysis results of RAPID software influenced the prognosis of EVT in patients with acute BAO (OR=4.048, 95%CI: 1.276-12.840). CONCLUSIONS: RAPID software based on CTP can be used for preoperative screening of patients with acute basilar artery occlusion to identify those suitable for endovascular treatment, which is worthy of clinical promotion.

MMP-10 rs17435959 Polymorphism is Associated with the Formation and Stability of Carotid Atherosclerosis Plaque: A Case-Control Study.

BACKGROUND: Matrix metalloproteinase 10 (MMP-10) has a close relationship with carotid atherosclerosis (CAS) and cerebral infarction. The MMP-10 rs17435959 polymorphism causes a leucine to valine transition at codon 4 in exon 1 of the MMP-10 gene and may have functional effects. OBJECTIVES: To investigate the relationship between the MMP-10 rs17435959 polymorphism and the formation and stability of CAS plaques. MATERIALS AND METHODS: The present case-control study contains 738 visitors who came to our health examination center for the first time. According to the carotid ultrasound examinations, visitors were classified into the vulnerable plaque group (41-86 years old, 141 male, 105 female), the stable plaque group (41-86 years old, 141 male, 105 female) and the no plaque group (41-85 years old, 141 male, 105 female). All visitors in the three groups were sex- and- age-matched, and cardiovascular and cerebrovascular diseases were absent. The polymorphism was genotyped by real-time polymerase chain reaction- restriction. RESULTS: Compared to the GG genotype, the frequency of the CC and CG genotypes was significantly more common in the vulnerable plaque group than in the no plaque group (18.7% vs. 7.7%, unadjusted P = 0.002). Moreover, compared to the G allele, the frequency of the C allele was significantly more common in the vulnerable plaque group than in the no plaque group (10.4% vs. 3.9%, unadjusted P = 0.000) and in the vulnerable plaque group than in the stable plaque group (10.4% vs. 5.1%, unadjusted P = 0.008). Binary logistic regression showed that the CC and CG genotype was independent risk factor for the formation (P = 0.019, OR = 1.961, 95% CI [1.117, 3.444]) and vulnerability (P = 0.035, OR = 1.842, 95% CI [1.045, 3.247]) of CAS plaques. Moreover, individuals who have the C allele showed a higher level of fibrinogen, which was an independent risk factor for the formation of CAS plaques (P = 0.000, OR = 2.425, 95% CI [1.475, 3.985]). CONCLUSIONS: The rs17435959 polymorphism was associated with the formation and vulnerability of CAS plaques. Individuals who had variant-type MMP-10 showed higher levels of fibrinogen, which promoted the formation of CAS plaques.

Association of obstructive sleep apnea with cognitive decline and age among non-demented older adults.

We aimed to investigate whether obstructive sleep apnea (OSA) status affects the relationship between cognitive decline and age among non-demented elderly people. A total of 1422 participants (493 normal cognition and 929 amnestic mild cognitive impairment) were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Based on the self-reported medical history of OSA, participants were categorized into two groups (OSA- and OSA +). Multiple linear regression models were performed to assess the effect of the OSA * Age interaction on MMSE, ADAS-cog11 and RAVLT immediate recall in non-demented group and in APOE ε4 carriers/non-carriers adjusting for gender and educational attainment. In the present study, the OSA + group demonstrated significant cognitive decline versus the OSA- group. In addition, in APOE ε4- group, our findings showed a significant OSA * age interaction for ADAS-cog11 and RVALT immediate recall, but not MMSE. No significant interaction was observed in the APOE ε4+ individuals. In conclusion, our findings implicate that OSA status may affect the association of age with cognitive impairment among non-demented older people.

Intratumoral Injection of Anlotinib Hydrogel Combined With Radiotherapy Reduces Hypoxia in Lewis Lung Carcinoma Xenografts: Assessment by Micro Fluorine-18-fluoromisonidazole Positron Emission Tomography/Computed Tomography Hypoxia Imaging.

Hypoxia is a common feature of solid tumors that increases tumor invasiveness and resistance to radiotherapy (RT) and chemotherapy. Local application of anlotinib (AL) might increase the regulation of new blood vessel growth and improve tumor hypoxia in RT. Therefore, it is essential to fully understand the drug delivery system of AL. Herein, we applied hypoxia imaging using micro fluorine-18-fluoromisonidazole positron emission tomography/computed tomography (micro 18F-FMISO PET/CT) to assess responses to intratumoral injections of an AL hydrogel (AL-HA-Tyr) combined with RT in mice bearing Lewis lung carcinoma (LLC). We formed AL-HA-Tyr by encapsulating AL with hyaluronic acid-tyramine (HA-Tyr) conjugates via the oxidative coupling of tyramine moieties catalyzed by H2O2 and horseradish peroxidase. AL-HA-Tyr restrained the proliferation of human umbilical endothelial cells (HUVECs) in colony formation assays in vitro (p < 0.001). We established a subcutaneous LLC xenograft model using C57BL/6J mice that were randomly assigned to six groups that were treated with AL, HA-Tyr, AL-HA-Tyr, RT, and RT+AL-HA-Tyr, or untreated (controls). Tumor volume and weight were dynamically measured. Post treatment changes in hypoxia were assessed in some mice using micro 18F-FMISO PET/CT, and survival was assessed in others. We histopathologically examined toxicity in visceral tissues and Ki-67, VEGF-A, γ-H2AX, and HIF-1α expression using immunohistochemistry. Direct intratumoral injections of AL-HA-Tyr exerted anti-tumor effects and improved hypoxia like orally administered AL (p > 0.05), but reduced visceral toxicity and prolonged survival. The uptake of 18F-FMISO did not significantly differ among the AL, AL-HA-Tyr, and RT+AL-HA-Tyr treated groups. Compared with the other agents, RT+AL-HA-Tyr decreased HIF-1α, Ki67, and VEGF-A expression, and increased γ-H2AX levels in tumor cells. Overall, compared with AL and AL-HA-Tyr, RT+AL-HA-Tyr improved tumor hypoxia, enhanced anti-tumor effects, and prolonged the survival of mice bearing LLC.