Dose-Response Relationship between C-Reactive Protein/Albumin Ratio and In-Hospital Mortality in Elderly Patients with Acute Ischemic Stroke.

INTRODUCTION: The C-reactive protein/albumin ratio is a reliable indicator of outcome risk in several diseases. This study aims to evaluate prognostic power of the C-reactive protein/albumin ratio for in-hospital mortality and the dose-response relationship between the two in the oldest-old patients with acute ischemic stroke. METHODS: A longitudinal observational study was conducted on patients with acute ischemic stroke (aged ≥80 years) from two tertiary hospitals between January 1, 2014, and January 31, 2020. Based on the tertiles of the C-reactive protein/albumin ratio, the patients were divided into three groups. Restrictive cubic spline and robust locally weighted regression analysis were performed on continuous variables to examine the dose-response relationship between the C-reactive protein/albumin ratio and in-hospital mortality risk. All-cause mortality during hospitalization was the outcome for this study. RESULTS: The study included 584 patients (mean age = 84.6 ± 3.1 years; 59.6% men). The C-reactive protein/albumin ratio was divided into three groups, namely, T1 of <0.73, T2 of 0.73-2.03, and T3: >2.03. After adjusting for demographic and clinical characteristics, a higher C-reactive protein/albumin ratio was independently associated with in-hospital mortality. The hazard ratio for this association was 2.01 (95% confidence interval: 1.12-3.60, p = 0.019). A dose-response relationship between the C-reactive protein/albumin ratio and in-hospital mortality risk was observed. Sensitivity analysis found no attenuation in the hazard ratio in uninfected individuals, whereas no difference in the hazard ratio was noted in individuals with infections. CONCLUSIONS: When predicting in-hospital mortality in the oldest-old patients with ischemic stroke, the C-reactive protein/albumin ratio might be a helpful and convenient metric.

Proteomics revealed an association between ribosome-associated proteins and amyloid beta deposition in Alzheimer's disease.

Most scholars believe that amyloid-beta (Aß) has the potential to induce apoptosis, stimulate an inflammatory cascade, promote oxidative stress and exacerbate the pathological progression of Alzheimer's disease (AD). Therefore, it is crucial to investigate the deposition of Aß in AD. At approximately 6 months of age, APP/PS1 double transgenic mice gradually exhibit the development of plaques, as well as spatial and learning impairment. Notably, the hippocampus is specifically affected in the course of AD. Herein, 6-month-old APP/PS1 double transgenic mice were utilized, and the differentially expressed (DE) proteins in the hippocampus were identified and analyzed using 4D label-free quantitative proteomics technology and parallel reaction monitoring (PRM). Compared to wild-type mice, 29 proteins were upregulated and 25 proteins were downregulated in the AD group. Gene Ontology (GO) enrichment analysis of biological processes (BP) indicated that the DE proteins were mainly involved in 'ribosomal large subunit biogenesis'. Molecular function (MF) analysis results were primarily associated with '5.8S rRNA binding' and 'structural constituent of ribosome'. In terms of cellular components (CC), the DE proteins were mainly found in 'polysomal ribosome', 'cytosolic large ribosomal subunit', 'cytosolic ribosome', and 'large ribosomal subunit', among others. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the results were mainly enriched in the 'Ribosome signaling pathway'. The key target proteins identified were ribosomal protein (Rp)l18, Rpl17, Rpl19, Rpl24, Rpl35, and Rpl6. The PRM verification results were consistent with the findings of the 4D label-free quantitative proteomics analysis. Overall, these findings suggest that Rpl18, Rpl17, Rpl19, Rpl24, Rpl35, and Rpl6 may have potential therapeutic value for the treatment of AD by targeting Aß.

Trumpet-Like ZnS@C Composite for High-Performance Potassium Ion Battery Anode.

ZnS has acquired increasing attention for high-performance PIBs anode because of its remarkable theoretical capacity, and redox reversibility for conversion reaction. However, the larger volume variation and delayed reaction kinetics for the ZnS in the discharge/charge processes lead to pulverization and severe capacity degradation. Herein, the trumpet-like ZnS@C composite was synthesized by template method by using sodium citrate as carbon source followed by vulcanization process. As potassium ion batteries (PIB) anode, ZnS@C composite exhibits good rate performance and long life (stable reversible capacity of 107.8 mAh/g over 2000 charge-discharge cycles at 5 A/g and high reversible capacity of 310 mAh/g at 0.1 A/g). The outstanding electrochemical performance of the ZnS@C composite is ascribed to its unique structure, which can mitigate the volume expansion of ZnS in the charge discharge process, expand the contact area between the electrode and electrolyte, and improve the conductivity of electrode materials by the introduction of carbon layer. This method of synthesizing trumpet-like ZnS@C composite provides an important strategy for obtaining potassium ion batteries anode with long cycle.

Dose-Response Relationship between Red Blood Cell Distribution Width and In-Hospital Mortality in Oldest Old Patients with Acute Ischemic Stroke.

INTRODUCTION: It is crucial to identify predictors of mortality in the early stage of acute ischemic stroke for the oldest old (aged ≥80 years) because of their poor overall survival outcomes. However, limited data are available as the oldest old have often been excluded from previous clinical studies. Hence, we aimed to assess the predictive effect of red blood cell distribution width on in-hospital mortality and the dose-response relationship between the red blood cell distribution width and in-hospital mortality in oldest old with acute ischemic stroke. METHODS: A retrospective cohort study was performed in two tertiary hospitals. Patients aged ≥80 years admitted due to acute ischemic stroke from January 1, 2014, to January 31, 2020, were included in the study. We divided the eligible patients into 3 groups with tertiles of red blood cell distribution width. Restrictive cubic spline and robust locally weighted regression analysis were performed to test the dose-response relationship between red blood cell distribution width and the in-hospital mortality risk. All-cause in-hospital mortality was the main study outcome. RESULTS: Overall, 606 patients were included in the final analysis. Red blood cell distribution width was categorized into 3 groups (T1: <13.7%, T2: 13.8-15.7%, and T3: >15.7%). The rationality of this categorization was then validated with restricted cubic spline and robust locally regression smoothing scatterplot, respectively. After adjusting for demographic and clinical features, a higher red blood cell distribution width was independently associated with in-hospital mortality and the hazard ratio (HR) was 3.31 (95% CI 2.47-4.45, p < 0.001). There was a positive dose-response relationship between red blood cell distribution width and mortality risk. Sensitivity analysis identified no conspicuous change in the HR. CONCLUSIONS: Red blood cell distribution width may be a valuable and simple measure for predicting in-hospital mortality in oldest old patients with acute ischemic stroke.

Exploring the therapeutic mechanism of Banxia Xiexin Decoction in mild cognitive impairment and diabetes mellitus: a network pharmacology approach.

The incidence of mild cognitive impairment (MCI) and diabetes mellitus (DM) is increasing year by year. Clinical findings show that Banxia Xiexin Decoction (BXD) can be combined to treat MCI and DM. However, the principle and mechanism of BXD in treating MCI and DM remain unclear. In this study, to explore the common mechanism of BXD in treating MCI and DM by using the method of network pharmacology. Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) was used to screen the main active components of BXD, as well as to predict and screen its potential targets. Using Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), DisGeNET, GeneCards to select the target proteins of two diseases, and intersecting the drug target and the disease target to obtain the common target of drug diseases, which is imported into cytoscape software to draw the network diagram of "drug components-target diseases" and the interaction network diagram between the common target proteins. According to the Database for Annotation, Visualization and Integrated Discovery (DAVID) database, we analyzed the common targets using two methods, gene ontology Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway enrichment analysis and Gene Ontology (GO) function enrichment analysis, as well as studied the interaction mechanism of the two diseases, with the results validated using molecular docking. A total of 267 main active components of BXD were screened, together with the two diseases shared 233 common targets. The top five key targets identified by the topological analysis were TP53, AKT1, STAT3, TNF, and MAPK3. Go enrichment results indicated that it was primarily related to response to drug, extracellular space, enzyme binding, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding. t KEGG enrichment pathway analysis identified 20 significant pathways, the majority of which are AGE-RAGE signaling pathways in diabetic complications, lipid and atherosclerosis, fluid shear stress and atherosclerosis, IL-17 signaling pathway, TNF signaling pathway, and so on. The results of molecular docking revealed that the key components of BXD, baicalein, licochalcone a, quercetin, and naringenin, had strong binding ability with core targets TP53, AKT1, STAT3, TNF, MAPK3. BXD can treat MCI and DM by multi-targets and multi-channels,and plays a role of "homotherapy for heteropathy" mainly through response to drug, positive regulation of gene expression, extracellular space and enzyme binding and other ways.

Distributed Refractive Index Sensing Based on Etched Ge-Doped SMF in Optical Frequency Domain Reflectometry.

A distributed optical fiber refractive index sensor based on etched Ge-doped SMF in optical frequency domain reflection (OFDR) was proposed and demonstrated. The etched Ge-doped SMF was obtained by only using wet-etching, i.e., hydrofluoric acid solution. The distributed refractive index sensing is achieved by measuring the spectral shift of the local RBS spectra using OFDR. The sensing length of 10 cm and the spatial resolution of 5.25 mm are achieved in the experiment. The refractive index sensing range is as wide as 1.33-1.44 refractive index units (RIU), where the average sensitivity was about 757 GHz/RIU. Moreover, the maximum sensitivity of 2396.9 GHZ/RIU is obtained between 1.43 and 1.44 RIU.

The protection effect of rhodionin against methicillin-resistant Staphylococcus aureus-induced pneumonia through sortase A inhibition.

Methicillin-resistant Staphylococcus aureus (MRSA) is a zoonotic antibiotic-resistant pathogen that negatively impacts society from medical, veterinary, and societal standpoints. The search for alternative therapeutic strategies and innovative anti-infective agents is urgently needed. Among the pathogenic mechanisms of Staphylococcus aureus (S. aureus), sortase A is a virulence factor of great concern because it is highly linked with the ability of MRSA to invade the host. In this study, we identified that rhodionin, a natural compound of flavonoid glucosides, effectively inhibited the activity of SrtA without affecting the survival and growth of bacteria, and its half maximal inhibitory concentration (IC50) value was 22.85 µg/mL. In vitro, rhodionin prominently attenuated the virulence-related phenotype of SrtA by reducing the adhesion of S. aureus to fibrinogen, reducing the capacity of protein A (SpA) on the bacterial surface and biofilm formation. Subsequently, fluorescence quenching and molecular docking were performed to verify that rhodionin directly bonded to SrtA molecule with KA value of 6.22 × 105 L/mol. More importantly, rhodionin showed a significant protective effect on mice pneumonia model and improved the survival rate of mice. According to the above findings, rhodionin achieved efficacy in the treatment of MRSA-induced infections, which holds promising potential to be developed into a candidate used for MRSA-related infections.

Clinical characteristics of moderate COVID-19 patients aggravation in Wuhan Stadium Cabin Hospital: A 571 cases of retrospective cohort study.

To report the clinical characteristics and potential risk factors of patients with coronavirus disease 2019 (COVID-19) in Wuhan Stadium Cabin Hospital in Hubei Province. A total of 571 patients of COVID-19 treated in the Wuhan Stadium Cabin Hospital were selected for analysis, univariable and multivariable logistic regression methods were used to explore the risk factors associated with disease aggravation. The main clinical symptoms of moderate COVID-19 were fever, cough and dyspnea, hypertension, diabetes, and coronary heart diseases were the main comorbidities both in transferred and stable patients. Twenty-six patients (4.55%) of mild and moderate patients had disease aggravation, and most of which occurred between 36 and 48 hours after admission. Multiple regression analysis showed increasing odds of disease aggravation associated with former smoker history, diabetes, dyspnea, consolidation, and interstitial abnormalities of computed tomography scanning, lymphopenia and elevated of C-reactive protein, the time points of transferred patients mainly between 36 and 48 hours (65.38%), and the average hospital stay for stable patients was 15 days.It could help clinicians to identify patients with poor prognosis at an early stage, and provide early warning role for timely intervention.

Admission Hemoglobin Is Prognostic for In-Hospital Mortality in Oldest-Old Patients with Acute Ischemic Stroke.

INTRODUCTION: Anemia is a common condition encountered in acute ischemic stroke, and only a few pieces of evidence has been produced suggesting its possible association with short-term mortality have been produced. The study sought to assess whether admission anemia status had any impact on short-term clinical outcome among oldest-old patients with acute ischemic stroke. MATERIALS AND METHODS: A retrospective review of Electronic Medical Recording System was performed in 2 tertiary hospitals. Data, from the oldest-old patients aged > = 80 years consecutively admitted with a diagnosis of acute ischemic stroke between January 1, 2015, and December 31, 2019, were analyzed. Admission hemoglobin was used as indicator for anemia and severity. Univariate and multivariate regression analyses were used to compare in-hospital mortality and length of in-hospital stay in different anemia statuses and normal hemoglobin patients. RESULTS: A total of 705 acute ischemic stroke patients were admitted, and 572 were included in the final analysis. Of included patients, 240 of them were anemic and 332 nonanemic patients. A statistical difference between the 2 groups was found in in-hospital mortality (p < 0.001). After adjustment for baseline characteristics, the odds ratio value of anemia for mortality were 3.91 (95% confidence intervals (CI) 1.60-9.61, p = 0.003) and 7.15 (95% CI: 1.46-34.90, p = 0.015) in moderate and severely anemic patients, respectively. Similarly, length of in-hospital stay was longer in anemic patients (21.64 ± 6.17 days) than in nonanemic patients (19.08 ± 5.48 days, p < 0.001). CONCLUSIONS: Increased severity of anemia may be an independent risk factor for increased in-hospital mortality and longer length of stay in oldest-old patients with acute ischemic stroke.

Neuronal Apoptosis Preventive Potential of Sophocarpine via Suppression of Aß-Accumulation and Down-Regulation of Inflammatory Response.

In the current study sophocarpine was investigated in vitro for prevention of ß-amyloid induced PC12 neuronal cell damage. Exposure to ß-amyloid caused a dose-dependent suppression in growth of PC12 cells with maximum reduction at 10 µM. Sophocarpine pre-treatment reversed suppressive effect of ß-amyloid (10 µM) on PC12 cell growth in concentration-based manner. In sophocarpine pre-treated PC12 cells the ß-amyloid mediated PGE2 level elevation was attenuated significantly at 0.25-2 µM doses. Moreover, in sophocarpine pretreated PC12 cells the ß-amyloid mediated promotion of COX-2 level was also inhibited. Sophocarpine pre-treatment attenuated iNOS expression in ß-amyloid exposed PC12 cells at 0.25-2 µM doses. Pre-treatment of PC12 cells with sophocarpine suppressed NO-species generation induced by ß-amyloid exposure. In sophocarpine pretreated PC12 cells elevation of nuclear NF-κB expression induced by ß-amyloid was significantly inhibited. In summary, sophocarpine prevents reduction of PC12 cell growth induced by ß-amyloid exposure via inhibition of inflammatory processes. The preventive effect of sophocarpine on ß-amyloid induced PC12 cell damage is associated with inhibition of NF-κB nuclear translocation. Therefore, sophocarpine may be used for treatment of neurological disorders like Alzheimer's disease.

Admission serum cholinesterase concentration for prediction of in-hospital mortality in very elderly patients with acute ischemic stroke: a retrospective study.

BACKGROUND: Cholinesterase as a sensitive biomarker for prognosis in a variety of conditions but it is rare in stroke studies. The very elderly (≥ 80 years of age) represent the most susceptible group of ischemic stroke. We aimed to determine whether admission serum cholinesterase concentration had any effect on clinical outcome in very elderly patients (individuals aged ≥ 80 years) with acute ischemic stroke. METHODS: A retrospective record review was conducted in two tertiary university hospitals. Elderly patients aged ≥ 80 years admitted with a diagnosis of acute ischemic stroke from January 1, 2014 to November 30, 2019, who had a cholinesterase concentration drawn, were included. The patients were grouped based on the inflection points of the locally weighted regression and smoothing scatterplot (LOESS) curve between cholinesterase levels and in-hospital mortality (study outcome) with lower concentration as reference group. RESULTS: A total of 612 patients were admitted with a diagnosis of acute ischemic stroke, and 569 met the inclusion criteria. A threshold effect was identified using regression smoothing scatterplot (LOESS), with one cutoff point of 4.0 KU/L. There was a significant difference in-hospital mortality was observed (P < 0.001). After adjusted demographic and clinical features, the OR of cholinesterase for mortality was 0.43 (95% CI 0.34-0.54, P < 0.001), suggesting that lower admission cholinesterase level was an independent risk factors for all-cause mortality among patients with AIS. CONCLUSIONS: We have demonstrated a significant association between admission cholinesterase concentration and in-hospital mortality in very elderly patients with AIS.

Development and validation of a prediction rule for estimating gastric cancer risk in the Chinese high-risk population: a nationwide multicentre study.

OBJECTIVE: To develop a gastric cancer (GC) risk prediction rule as an initial prescreening tool to identify individuals with a high risk prior to gastroscopy. DESIGN: This was a nationwide multicentre cross-sectional study. Individuals aged 40-80 years who went to hospitals for a GC screening gastroscopy were recruited. Serum pepsinogen (PG) I, PG II, gastrin-17 (G-17) and anti-Helicobacter pylori IgG antibody concentrations were tested prior to endoscopy. Eligible participants (n=14 929) were randomly assigned into the derivation and validation cohorts, with a ratio of 2:1. Risk factors for GC were identified by univariate and multivariate analyses and an optimal prediction rule was then settled. RESULTS: The novel GC risk prediction rule comprised seven variables (age, sex, PG I/II ratio, G-17 level, H. pylori infection, pickled food and fried food), with scores ranging from 0 to 25. The observed prevalence rates of GC in the derivation cohort at low-risk (≤11), medium-risk (12-16) or high-risk (17-25) group were 1.2%, 4.4% and 12.3%, respectively (p<0.001).When gastroscopy was used for individuals with medium risk and high risk, 70.8% of total GC cases and 70.3% of early GC cases were detected. While endoscopy requirements could be reduced by 66.7% according to the low-risk proportion. The prediction rule owns a good discrimination, with an area under curve of 0.76, or calibration (p<0.001). CONCLUSIONS: The developed and validated prediction rule showed good performance on identifying individuals at a higher risk in a Chinese high-risk population. Future studies are needed to validate its efficacy in a larger population.

[Exploring Chinese medicine and Western medicine group modules in acute phase of ischemic stroke disease].

Under the theoretical guidance of "combination of disease and syndrome， correspondence between syndrome and prescription， and dynamic space-time"， 11 135 acute ischemic stroke patients were collected from hospital information system(HIS) of many 3A grade hospitals of traditional Chinese medicine. Complex network analysis was adopted to obtain the core syndrome elements in different periods of acute ischemic stroke patients， and it was found that the core syndrome elements were blood stasis syndrome， phlegm， endogenous wind， Yin deficiency， Qi deficiency， heat， hyperactivity of liver Yang， liver， and kidney of patients in hospital for the first day， and during 8-14 d in hospitalization， the core syndrome elements were blood stasis， phlegm， Yin deficiency， Qi deficiency， endogenous wind， hyperactivity of liver Yang， liver， and kidney. The data with "improved" and "cured" treatment outcomes were adopted for complex network analysis and correlation analysis to identify the Chinese and Western medicine group modules in patients with different disease conditions in different phases after hospitalization. It was found that the Chinese and Western medicine modules within 14 d after hospitalization mainly included "blood-activating and stasis-dissolving module "consisted by "anti-platelet drug + circulation-improving medicine(or anticoagulant drug and anti-fibrinogen drug， et al) + blood-activating and stasis-dissolving drugs"， as well as "stasis-dissolving and phlegm-reducing module" consisted by "anti-platelet drugs + circulation-improving medicine(or anticoagulant drug and anti-fibrinogen drug， et al) + phlegm refreshing drug". The core Chinese and Western medicine modules in patients with urgent and general conditions within 7 d after hospitalization mainly used "blood-activating and stasis-dissolving module" and "stasis-dissolving and phlegm-reducing module". Three or more Chinese medicine and Western medicines module with more than 1% utilization rate was not found in the patients with critical disease condition in admission. The urgent， general and critically ill patients in admission mainly used "blood-activating and stasis-dissolving module" in 8-14 d. From the real world medical big data research， it was found that the combined use of Chinese and Western medicines were consistent with "combination of disease and syndrome， correspondence between syndrome and prescription， and dynamic space-time" theory， and multiple multidimensional dynamic Chinese medicine and Western medicine group modules of "patient-syndrome-drug-time-effective" at the acute ischemic stroke stage were dug out， forming the method of Chinese and Western medicine combination research based on electrical medical big data.

[Intensive hospital monitoring of Shuxuening injection in 30 209 cases].

In order to obtain the characteristics and incidence of adverse reactions of Shuxuening injection (Xingxue), the design method of a multi-center, large sample intensive monitoring in the hospitals was adopted. The hospitalized patients with use of Shuxuening injection from 27 medical institutions were enrolled as the research subjects to monitor their entire process of treatment cycle. The main content of monitoring included the patients' general information, diagnostic information, medication information, and adverse event information. A total of 30 209 patients with Shuxuening injection were enrolled; adverse reactions occurred in 34 cases, with an incidence of 0.113%, which belonged to the rare adverse reactions. Adverse reactions were characterized by headache, dizziness, pruritus, palpitations, nausea, et al. All the above results showed that Xingxue Shuxuening injection had high safety in clinical application.

[Incidence rate of adverse reaction/event by Qingkailing injection: a Meta-analysis of single rate].

To systematically review the incidence rate of adverse drug reaction/event by Qingkailing injection. Such databases as the PubMed, EMbase, the Cochrane library, CNKI, VIP WanFang data and CBM were searched by computer from foundation to July 30, 2015. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and cross check data. Then, Meta-analysis was performed by using the R 3.2.0 software, subgroup sensitivity analysis was performed based on age, mode of medicine, observation time and research quality. Sixty-three studies involving 9,793 patients with Qingkailing injection were included, 367 cases of adverse reactions/events were reported in total. The incidence rate of adverse reaction in skin and mucosa group was 2% [95% CI (0.02; 0.03)]; the digestive system adverse reaction was 6% [95% CI(0.05; 0.07); the injection site adverse reaction was 4% [95% CI (0.02; 0.07)]. In the digestive system as the main types of adverse reactions/events, incidence of children and adults were 4.6% [0.021 1; 0.097 7] and 6.9% [0.053 5; 0.089 8], respectively. Adverse reactions to skin and mucous membrane damage as the main performance/event type, the observation time > 7 days and ≤ 7 days incidence of 3% [0.012 9; 0.068 3] and 1.9% [0.007 8; 0.046 1], respectively. Subgroup analysis showed that different types of adverse reactions, combination in the incidence of adverse reactions/events were higher than that of single drug, the difference was statistically significant (P < 0.05). This study suggested the influence factors of adverse reactions occur, and clinical rational drug use, such as combination, age and other fators, and the influence factors vary in different populations. Therefore, clinical doctors for children and the elderly use special care was required for a clear and open spirit injection, the implementation of individualized medication.

Influence of surface cracks on laser-induced damage resistance of brittle KH2PO4 crystal.

Single point diamond turning (SPDT) currently is the leading finishing method for achieving ultra-smooth surface on brittle KH(2)PO(4) crystal. In this work, the light intensification modulated by surface cracks introduced by SPDT cutting is numerically simulated using finite-difference time-domain algorithm. The results indicate that the light intensification caused by surface cracks is wavelength, crack geometry and position dependent. Under the irradiation of 355 nm laser, lateral cracks on front surfaces and conical cracks on both front and rear surfaces can produce light intensification as high as hundreds of times, which is sufficient to trigger avalanche ionization and finally lower the laser damage resistance of crystal components. Furthermore, we experimentally tested the laser-induced damage thresholds (LIDTs) on both crack-free and flawed crystal surfaces. The results imply that brittle fracture with a series of surface cracks is the dominant source of laser damage initiation in crystal components. Due to the negative effect of surface cracks, the LIDT on KDP crystal surface could be sharply reduced from 7.85J/cm(2) to 2.33J/cm(2) (355 nm, 6.4 ns). In addition, the experiment of laser-induced damage growth is performed and the damage growth behavior agrees well with the simulation results of light intensification caused by surface cracks with increasing crack depths.

Advances in the Understanding of the Correlation Between Neuroinflammation and Microglia in Alzheimer's Disease.

Alzheimer's disease (AD) is a fatal neurodegenerative disease with a subtle and progressive onset and is the most common type of dementia. However, its etiology and pathogenesis have not yet been fully elucidated. The common pathological manifestations of AD include extraneuronal ß-amyloid deposition (Aß), intraneuronal tau protein phosphorylation leading to the formation of 'neurofibrillary tangles' (NFTs), neuroinflammation, progressive loss of brain neurons/synapses, and glucose metabolism disorders. Current treatment approaches for AD primarily focus on the 'Aß cascade hypothesis and abnormal aggregation of hyperphosphorylation of tau proteins', but have shown limited efficacy. Therefore, there is an ongoing need to identify more effective treatment targets for AD. The central nervous system (CNS) inflammatory response plays a key role in the occurrence and development of AD. Neuroinflammation is an immune response activated by glial cells in the CNS that usually occurs in response to stimuli such as nerve injury, infection and toxins or in response to autoimmunity. Neuroinflammation ranks as the third most prominent pathological feature in AD, following Aß and NFTs. In recent years, the focus on the role of neuroinflammation and microglia in AD has increased due to the advancements in genome-wide association studies (GWAS) and sequencing technology. Furthermore, research has validated the pivotal role of microglia-mediated neuroinflammation in the progression of AD. Therefore, this article reviews the latest research progress on the role of neuroinflammation triggered by microglia in AD in recent years, aiming to provide a new theoretical basis for further exploring the role of neuroinflammation in the process of AD occurrence and development.

Association between blood urea nitrogen to creatinine ratio and 3-month outcome in patients with acute ischaemic stroke: a retrospective cohort study from a large healthcare system.

OBJECTIVES: The blood urea nitrogen to creatinine (BUN/Cr) ratio is associated with early neurological deterioration in acute ischaemic stroke (AIS). However, the predictive value of the BUN/Cr ratio for the AIS prognosis remains unclear. Therefore, we evaluated the correlation between the BUN/Cr ratio and the 3-month outcome in patients with AIS, further testing their dose-response relationship. DESIGN: This retrospective cohort study enrolled patients with AIS who were admitted between 1 January 2013 and 31 May 2022. Poor clinical outcome was defined as 3-month Modified Rankin Scale (mRS) >2. Cox proportional HR was used to evaluate the correlation between the BUN/Cr ratio and 3-month outcome. Restricted cubic spline and robust locally weighted regression analyses were conducted to determine the dose-response relationship between the BUN/Cr ratio and the 3-month outcome. RESULTS: A total of 4952 eligible patients were included in the study. The patients were divided into three groups according to the tertiles of BUN/Cr ratio (T1, <0.071; T2, 0.071-0.093; and T3, >0.093). After logistic regression adjustment for demographic and clinical characteristics, the BUN/Cr ratio was found to be independently associated with the 3-month outcome in patients with AIS. The restricted cubic spline and locally regression smoothing scatterplot graph showed a strong dose-response relationship between the BUN/Cr ratio and the 3-month outcome in patients with AIS. CONCLUSION: A dose-response relationship was observed between the BUN/Cr ratio and the 3-month outcome in patients with AIS, suggesting that the BUN/Cr ratio could serve as a reliable predictor for the AIS prognosis.

Ferroptosis mechanism and Alzheimer's disease.

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms. This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms. Ferroptosis is a classic regulatory mode of cell death. Extensive studies of regulatory cell death in Alzheimer's disease have yielded increasing evidence that ferroptosis is closely related to the occurrence, development, and prognosis of Alzheimer's disease. This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferroptosis in Alzheimer's disease. Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer's disease.

Fabrication of spherical mitigation pit on KH2PO4 crystal by micro-milling and modeling of its induced light intensification.

Micro-machining is the most promising method for KH(2)PO(4) crystal to mitigate the surface damage growth in high power laser system. In this work, spherical mitigation pit is fabricated by micro-milling with an efficient machining procedure. The light intensification caused by rear surface features before and after mitigation is numerically modeled based on the finite-difference time-domain method. The results indicate that the occurrence of total internal reflections should be responsible for the largest light intensification inside the crystal. For spherical pits after mitigation, the light intensification can be greatly alleviated by preventing the occurrence of total internal reflections. The light intensification caused by spherical mitigation pit is strongly dependent on the width-depth ratio and it is suggested that the width-depth ratio of spherical mitigation pit must be devised to be larger than 5.0 to achieve the minimal light intensification for the mitigation of surface damage growth. Laser damage tests for KH(2)PO(4) crystal validate that the laser damage resistance of initially damaged surface can be retrieved to near the level of ideal surface by replacing initial damage site with predesigned mitigation pit.