Simvastatin Enhances Immune Responses to Aβ Vaccination and Attenuates Vaccination-Induced Behavioral Alterations

Statins are widely used to lower cholesterol levels by inhibiting cholesterol biosynthesis. Some evidence has indicated that statins might have therapeutic and preventive benefits for Alzheimer\u27s disease (AD). We and others also have shown the beneficial effect of statin treatment in reversing learning and memory deficits in animal models of AD. However, data from clinical trials are inconclusive. We previously documented that the adenovirus vector encoding 11 tandem repeats of Aβ1-6 fused to the receptor-binding domain (Ia) of Pseudomonas exotoxin A, AdPEDI-(Aβ1-6)(11), is effective in inducing an immune response against amyloid-β protein (Aβ) and reducing brain Aβ load in Alzheimer\u27s mouse models. In the present study, we examined whether the administration of simvastatin can modulate immune and behavioral responses of C57BL/6 mice to vaccination. Simvastatin was given to the animals as a diet admixture for four weeks, followed by nasal vaccination with AdPEDI-(Aβ1-6)(11) once per week for four weeks. The cholesterol-lowering action of simvastatin was monitored by measuring the cholesterol levels in plasma. Simvastatin significantly increased the number of the mice responding to vaccination compared with the mice receiving only AdPEDI-(Aβ1-6)(11). Immunoglobulin isotyping revealed that the vaccination predominantly induced Th2 immune responses. Simvastatin treatment prevented Aβ-induced production of IFN-γ in splenocytes. The adenovirus vaccination altered mouse behavior in T- and elevated plus-maze tests and simvastatin counteracted such behavioral changes. Our results indicate that simvastatin clearly enhances the immune responses of C57BL/6 mice to the nasal vaccination with AdPEDI-(Aβ1-6)(11). Simvastatin may be effective in preventing behavioral changes associated with vaccination

Network meta-analysis of first-line thrombectomy strategy for acute posterior circulation strokes: a preliminary evaluation for combined approach

ObjectiveThrombectomy may provide superior results compared to best medical care for acute posterior circulation strokes (PCS). Contact aspiration (CA), stent retriever (SR), and combined SR + CA (SRA) are commonly employed as first-line techniques. However, the optimal strategy and the role of SRA remain uncertain.MethodsSystematic searching was conducted in three databases (PubMed, Embase, and Cochrane). Network meta-analyzes were performed using random-effects models. The reperfusion and clinical outcomes were compared. Pooled outcomes were presented as odds ratios (OR) with 95% confidence intervals (CI). Rankograms with surface under the cumulative ranking curve (SUCRA) were calculated.ResultsSeventeen studies were included, involving a total of 645 patients who received first-line CA, 850 patients who received SR, and 166 patients who received SRA. Regarding final recanalization outcomes, both first-line SRA (OR = 3.2, 95%CI 1.4–11.0) and CA (OR = 2.1, 95%CI 1.3–3.7) demonstrated superiority over SR in achieving successful reperfusion [modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3], with values of SUCRA 91.1, 58.5, and 0.4%, respectively. In addition, first-line SRA showed an advantage in achieving final mTICI 2c/3 compared to CA (OR = 3.6, 95%CI 0.99–16.0) and SR (OR = 6.4, 95%CI 1.3–35.0), with SUCRA value of 98.0, 44.7, and 7.2%, respectively. Regarding reperfusion outcome after the first pass, SRA also achieved a higher rate of mTICI 3 than SR (OR = 4.1, 95%CI 1.3–14.0), while CA did not (SUCRA 97.4, 4.6, 48.0%). In terms of safety outcomes, first-line CA was associated with a lower incidence of symptomatic intracranial hemorrhage (sICH) compared to SR (OR = 0.38, 95%CI 0.1–1.0), whereas the SRA technique did not (SUCRA 15.6, 78.6, 55.9%). Regarding clinical prognosis, first-line CA achieved a higher proportion of functional independence (modified Rankin Scale (mRS) 0–2) at 90 days than SR (OR = 1.4, 95%CI 1.1–1.9), whereas SRA did not (SUCRA 90.5, 17.4, 42.1%).ConclusionFor acute PCS, a first-line CA strategy yielded better results in terms of final successful reperfusion and 90-day functional independence compared to SR. As the combined technique, first-line SRA was associated with superior first-pass and final reperfusion outcomes compared to SR. However, no significant difference was observed in functional independence achieved by first-line SRA compared to the other two strategies. Further high-quality studies are warranted

SATB2 shows different profiles between appendiceal adenocarcinomas ex goblet cell carcinoids and appendiceal/colorectal conventional adenocarcinomas: An immunohistochemical study with comparison to CDX2

Background: Special AT-rich sequence-binding protein 2 (SATB2) is a novel marker for colorectal adenocarcinomas but little is known about its expression in appendiceal adenocarcinomas. We aim to investigate SATB2 in these tumors and colorectal adenocarcinomas with comparison to CDX2. Methods: Immunohistochemical stains for SATB2 and CDX2 were performed in 49 appendiceal adenocarcinomas (23 conventional, 26 adenocarcinoma ex goblet cell carcinoids (AdexGCCs)) and 57 colorectal adenocarcinomas. Their expression was correlated with tumor differentiation and growth patterns. Results: SATB2 staining was positive in 26/26 (100%) appendiceal AdexGCCs and 15/23 (65%) appendiceal conventional adenocarcinomas (P = 0.001). Their mean percentage of SATB2-positive cells was 93% and 34%, respectively (P \u3c 0.0001). CDX2 staining was seen in 26/26 (100%) AdexGCCs and 22/23 (96%) appendiceal conventional adenocarcinomas (P = 0.4694). SATB2 and CDX2 showed similar staining in AdexGCCs but CDX2 labeled more tumor cells than SATB2 in conventional adenocarcinomas (mean 84% vs. 34%, P \u3c 0.0001). SATB2 and CDX2 staining was seen in 82% (47/57) and 96% (55/57) colorectal adenocarcinomas, respectively (P = 0.01). The mean percentage of cells positive for SATB2 and CDX2 was 48% and 91%, respectively (P \u3c 0.00001). Decreased SATB2 immunoreactivity was associated with non-glandular differentiation particularly signet ring cells in colorectal (P = 0.001) and appendiceal conventional adenocarcinomas (P = 0.04) but not in appendiceal AdexGCCs. Conclusions: SATB2 is a highly sensitive marker for appendiceal AdexGCCs with similar sensitivity as CDX2. In colorectal and appendiceal conventional adenocarcinomas, SATB2 is not as sensitive as CDX2 and its immunoreactivity is dependent on tumor differentiation

Selective on/off switching at room temperature of a magnetic bistable {Fe2Co2} complex with single crystal-to-single crystal transformation via intramolecular electron transfer

National Nature Science Foundation of China [21172084, 20802022]; Self-determined research funds of CCNU from the colleges' basic research and operation of MOE [CCNU13F006, CCNU11C01002]A cyano-bridged {Fe2Co2} complex shows reversible single crystal-to-single crystal transformation between diamagnetic and paramagnetic states switched specifically by losing and absorbing methanol at room temperature in the solid state. And the solvent loss form presents temperature- and pressure-induced intramolecular electron transfer behaviour

Original Article Benefit of a 360-degree horizontal turn following premedication with simethicone on image quality during gastroendoscopy: a randomized controlled trial

Abstract: Objectives: To investigate whether a 360-degree horizontal turn after oral premedication with simethicone improves the mucosal visibility during gastroendoscopic examination, and to determine the proper time to turn over the patient. Methods: This study involved 993 patients scheduled for gastroendoscopy. Just before gastroendoscopy，after oral premedication with simethicone, patients were randomly assigned to three groups：in Group A, patients waited for 20 min before gastroendoscopy; in Group B, patients were separately waited for 5/10/15/20 min and were then turned 360 degrees just before gastroendoscopy; in Group C, patients were immediately turned 360 degrees and then separately waited for 5/10/15/20 min before examination. The sum of the gastric mucosal visibility scores (MVS) was calculated after the examination. The MVS and proportion of images with higher visibility scores for the mucosal surface. Lower scores indicate better visibility of the mucosal surface. Results: In Groups B and Groups C, when waiting time more than 10 min had lower mean total MVS than Group A. The MVS of four subgroups of Group B were not different from those of Group C. Conclusion: Oral premedication with simethicone and immediately make a body posture change (turning over 360 degrees) then waiting for 10min can increase the image quality during gastroendoscopy and effectively decrease the premedication time

Blood pressure, body mass index and risk of cardiovascular disease in Chinese men and women

<p>Abstract</p> <p>Background</p> <p>It is still uncertain whether increased blood pressure (BP) has a stronger effect on the risk of cardiovascular disease (CVD) in lean persons than in obese persons. We tested it using a data set collected from a large cohort of Chinese adults.</p> <p>Methods</p> <p>Systolic and diastolic BP, body mass index (BMI) and other variables were measured in 169,871 Chinese men and women ≥ 40 years of age in 1991 using standard protocols. Follow-up evaluation was conducted in 1999-2000, with a response rate of 93.4%. Data were analyzed with Cox proportional hazards models.</p> <p>Results</p> <p>After adjusted for age, sex, cigarette smoking, alcohol consumption, high school education, physical inactivity, geographic region, and urbanization, we found that the effects of systolic or diastolic BP on risk of CVD generally increased with the increasing BMI levels (underweight, normal, overweight, and obese). For example, hazard ratios (HRs) and 95% confidence interval (CI) per 1- standard deviation (SD) increase in systolic BP within corresponding BMI levels were 1.27(1.21-1.33), 1.45(1.41-1.48), 1.52 (1.45-1.59) and 1.63 (1.51-1.76), respectively. Statistically significant interactions (P < 0.0001) were observed between systolic BP, diastolic BP and BMI in relation to CVD. In baseline hypertensive participants we found both obese men and women had higher risk of CVD than normal-weight persons. The multivariate-adjusted HRs(95%CI) were 1.23(1.03-1.47) and 1.20(1.02-1.40), respectively.</p> <p>Conclusion</p> <p>Our study suggests that the magnitude of the association between BP and CVD generally increase with increasing BMI. Hypertension should not be regarded as a less serious risk factor in obese than in lean or normal-weight persons in Chinese adults.</p

Lysolipids are prominent in subretinal drusenoid deposits, a high-risk phenotype in age-related macular degeneration

IntroductionAge related macular degeneration (AMD) causes legal blindness worldwide, with few therapeutic targets in early disease and no treatments for 80% of cases. Extracellular deposits, including drusen and subretinal drusenoid deposits (SDD; also called reticular pseudodrusen), disrupt cone and rod photoreceptor functions and strongly confer risk for advanced disease. Due to the differential cholesterol composition of drusen and SDD, lipid transfer and cycling between photoreceptors and support cells are candidate dysregulated pathways leading to deposit formation. The current study explores this hypothesis through a comprehensive lipid compositional analysis of SDD.MethodsHistology and transmission electron microscopy were used to characterize the morphology of SDD. Highly sensitive tools of imaging mass spectrometry (IMS) and nano liquid chromatography tandem mass spectrometry (nLC-MS/MS) in positive and negative ion modes were used to spatially map and identify SDD lipids, respectively. An interpretable supervised machine learning approach was utilized to compare the lipid composition of SDD to regions of uninvolved retina across 1873 IMS features and to automatically discern candidate markers for SDD. Immunohistochemistry (IHC) was used to localize secretory phospholipase A2 group 5 (PLA2G5). ResultsAmong the 1873 detected features in IMS data, three lipid classes, including lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE) and lysophosphatidic acid (LysoPA) were observed nearly exclusively in SDD while presumed precursors, including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidic acid (PA) lipids were detected in SDD and adjacent photoreceptor outer segments. Molecular signals specific to SDD were found in central retina and elsewhere. IHC results indicated abundant PLA2G5 in photoreceptors and retinal pigment epithelium (RPE). DiscussionThe abundance of lysolipids in SDD implicates lipid remodeling or degradation in deposit formation, consistent with ultrastructural evidence of electron dense lipid-containing structures distinct from photoreceptor outer segment disks and immunolocalization of secretory PLA2G5 in photoreceptors and RPE. Further studies are required to understand the role of lipid signals observed in and around SDD