Correction: Wang et al. Role of Berberine Thermosensitive Hydrogel in Periodontitis via PI3K/AKT Pathway In Vitro. Int. J. Mol. Sci. 2023, 24, 6364.

In the original publication, there was a mistake in Figure 3 as published [...].

Clinical and neuroimaging association between neuropsychiatric symptoms and nutritional status across the Alzheimer's disease continuum: a longitudinal cohort study.

OBJECTIVES: To investigate the association between neuropsychiatric symptoms (NPS) and nutritional status, and explore their shared regulatory brain regions on the Alzheimer's disease (AD) continuum. DESIGN: A longitudinal, observational cohort study. SETTING: Data were collected from the Chinese Imaging, Biomarkers, and Lifestyle study between June 1, 2021 and December 31, 2022. PARTICIPANTS: Overall, 432 patients on the AD continuum, including amnestic mild cognitive impairment and AD dementia, were assessed at baseline, and only 165 patients completed the (10.37 ± 6.08) months' follow-up. MEASUREMENTS: The Mini-Nutritional Assessment (MNA) and Neuropsychiatric Inventory (NPI) were used to evaluate nutritional status and NPS, respectively. The corrected cerebral blood flow (cCBF) measured by pseudo-continuous arterial spin labeling of the dietary nutrition-related brain regions was analyzed. The association between the NPS at baseline and subsequent change in nutritional status and the association between the changes in the severity of NPS and nutritional status were examined using generalized linear mixed models. RESULTS: Increased cCBF in the left putamen was associated with malnutrition, general NPS, affective symptoms, and hyperactivity (P < 0.05). The presence of general NPS (ß = -1.317, P = 0.003), affective symptoms (ß = -1.887, P < 0.001), and appetite/eating disorders (ß = -1.714, P < 0.001) at baseline were associated with a decline in the MNA scores during follow-up. The higher scores of general NPI (ß = -0.048), affective symptoms (ß = -0.181), and appetite/eating disorders (ß = -0.416; all P < 0.001) were longitudinally associated with lower MNA scores after adjusting for confounding factors. CONCLUSIONS: We found that baseline NPS were predictors of a decline in nutritional status on the AD continuum. The worse the severity of affective symptoms and appetite/eating disorders, the poorer the nutritional status. Furthermore, abnormal perfusion of the putamen may regulate the association between malnutrition and NPS, which suggests their potentially common neural regulatory basis.

Oxygen Self-Supplied Nanoplatform for Enhanced Photodynamic Therapy against Enterococcus Faecalis within Root Canals.

The successful treatment of persistent and recurrent endodontic infections hinges upon the eradication of residual microorganisms within the root canal system, which urgently needs novel drugs to deliver potent yet gentle antimicrobial effects. Antibacterial photodynamic therapy (aPDT) is a promising tool for root canal infection management. Nevertheless, the hypoxic microenvironment within the root canal system significantly limits the efficacy of this treatment. Herein, a nanohybrid drug, Ce6/CaO2/ZIF-8@polyethylenimine (PEI), is developed using a bottom-up strategy to self-supply oxygen for enhanced aPDT. PEI provides a positively charged surface, which enables precise targeting of bacteria. CaO2 reacts with H2O to generate O2, which alleviates the hypoxia in the root canal and serves as a substrate for Ce6 under 660 nm laser irradiation, leading to the successful eradication of planktonic Enterococcus faecalis (E. faecalis) and biofilm in vitro and, moreover, the effective elimination of mature E. faecalis biofilm in situ within the root canal system. This smart design offers a viable alternative for mitigating hypoxia within the root canal system to overcome the restricted efficacy of photosensitizers, providing an exciting prospect for the clinical management of persistent endodontic infection.

Biodegradation of Urethane Dimethacrylate-based materials (CAD/CAM resin-ceramic composites) and its effect on the adhesion and proliferation of Streptococcus mutans.

OBJECTIVE: To investigate whether urethane dimethacrylate (UDMA) -based dental restorative materials biodegrade in the presence of Streptococcus mutans (S. mutans) and whether the monomers affect the adhesion and proliferation of S. mutans in turn. METHODS: Cholesterol esterase and pseudocholinesterase-like activities in S. mutans were detected using p-nitrophenyl substrate. Two UDMA-based CAD/CAM resin-ceramic composites, Lava Ultimate (LU) and Vita Enamic (VE), and a light-cured UDMA resin block were co-cultured with S. mutans for 14 days. Their surfaces were characterized by scanning electron microscopy and laser microscopy, and the byproducts of biodegradation were examined by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS). Then, the antimicrobial components (silver nanoparticles with quaternary ammonium salts) were added to the UDMA resin block to detect whether the biodegradation was restrained. Finally, the effect of UDMA on biofilm formation and virulence expression of S. mutans was assessed. RESULTS: Following a 14-day immersion, the LU and UDMA resin blocks' surface roughness increased. The LU and VE groups had no UDMA or its byproducts discovered, according to the UPLC-MS/MS data, whereas the light-cured UDMA block group had UDMA, urethane methacrylate (UMA), and urethane detected. The addition of antimicrobial agents showed a significant reduction in the release of UDMA. Biofilm staining experiments showed that UDMA promoted the growth of S. mutans biofilm and quantitative real-time polymerase chain reaction results indicated that 50 µg/mL UDMA significantly increase the expression of gtfB, comC, comD, comE, and gbpB genes within the biofilm. CONCLUSIONS: UDMA in the light-cured resin can be biodegraded to produce UMA and urethane under the influence of S. mutans. The formation of early biofilm can be promoted and the expression of cariogenic genes can be up-regulated by UDMA. CLINICAL SIGNIFICANCE: This study focuses for the first time on whether UDMA-based materials can undergo biodegradation and verifies from a genetic perspective that UDMA can promote the formation of S. mutans biofilms, providing a reference for the rational use of UDMA-based materials in clinical practice.

Mediation of Regional Cerebral Blood Flow in the Relationship between Specific Gut Microbiota and Cognition in Vascular Cognitive Impairment.

BACKGROUND: Gut microbiota could affect the onset and development of vascular cognitive impairment (VCI) through modulating metabolic and immune pathways. However, the vascular mechanisms involved remain unclear. OBJECTIVE: To investigate the gut microbiota associated with VCI and examine the mediating effects of regional cerebral blood flow (CBF) to explore potential therapeutic targets for VCI. METHODS: This prospective study enrolled patients with VCI (n = 16) and healthy controls (n = 18) from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1 and June 30, 2022. The gut microbiota composition and diversity were determined by 16 S ribosomal RNA gene sequencing. The association between gut microbiota and Montreal Cognitive Assessment (MoCA) scores was determined using Spearman's correlation analysis. Regional CBF was calculated using pseudo-continuous arterial spin labeling. The mediating effects of regional CBF on the relationship between specific gut microbiota and cognition in VCI were investigated using mediation analysis. RESULTS: Compared to healthy controls, patients with VCI had significantly greater abundance of Bifidobacterium, Veillonella, R uminococcus gnavus , Fusobacterium, and Erysipelatoclostridium and smaller abundance of Collinsella. The abundance of Ruminococcus gnavus was negatively associated with MoCA scores in patients with VCI, with the CBF in the left hypothalamus, right hypothalamus, and left amygdala accounting for 63.96%, 48.22%, and 36.51%, respectively, of this association after adjusting for confounders. CONCLUSIONS: Ruminococcus gnavus is associated with cognition in VCI, which is strongly mediated by CBF in the bilateral hypothalamus and left amygdala. These findings highlight the potential regulatory roles of nutrition and metabolism-related areas of the brain in VCI.

Development and validation of a nutrition-related genetic-clinical-radiological nomogram associated with behavioral and psychological symptoms in Alzheimer's disease.

BACKGROUND: Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism. METHODS: This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demoimagedatas, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram. RESULTS: Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. CONCLUSION: A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD. REGISTRATION: Chictr.org.cn, ChiCTR2100049131.

Chain Mediation Analysis of the Effects of Nutrition and Cognition on the Association of Apolipoprotein E ɛ4 with Neuropsychiatric Symptoms in Alzheimer's Disease.

BACKGROUND: Apolipoprotein E (APOE) is the most recognized risk gene for cognitive decline and clinical progression of late-onset Alzheimer's disease (AD); nonetheless, its association with neuropsychiatric symptoms (NPSs) remains inconclusive. OBJECTIVE: To investigate the association of APOE ɛ4 with NPSs and explore nutritional status and cognition as joint mediators of this association. METHODS: Between June 2021 and October 2022, patients with amnestic mild cognitive impairment (aMCI) or AD were recruited from the Chinese Imaging, Biomarkers, and Lifestyle Study. NPSs were assessed using the Neuropsychiatric Inventory, while global cognition and nutritional status were evaluated using the Mini-Mental State Examination (MMSE) and Mini-Nutritional Assessment (MNA), respectively. Simple mediation and multiple chain mediation models were developed to examine the mediating effects of the MNA and MMSE scores on the relationship between APOE ɛ4 and specific neuropsychiatric symptom. RESULTS: Among 310 patients, 229 (73.87%) had NPSs, and 110 (35.48%) carried APOE ɛ4. Patients with APOE ɛ4 were more likely to have hallucinations (p = 0.014), apathy (p = 0.008), and aberrant motor activity (p = 0.018). MNA and MMSE scores mediated the association between APOE ɛ4 and hallucinations (17.97% and 37.13%, respectively), APOE ɛ4 and apathy (30.73% and 57.72%, respectively), and APOE ɛ4 and aberrant motor activity (17.82% and 34.24%), respectively. Chain-mediating effects of MNA and MMSE scores on the association of APOE ɛ4 with hallucinations, apathy, and aberrant motor activity after adjusting for confounding factors were 6.84%, 11.54%, and 6.19%, respectively. CONCLUSION: Nutritional status and cognition jointly mediate the association between APOE ɛ4 and neuropsychiatric symptoms in patients with aMCI or AD.

Spatiotemporal Characteristics of Regional Brain Perfusion Associated with Neuropsychiatric Symptoms in Patients with Alzheimer's Disease.

BACKGROUND: Current technology for exploring neuroimaging markers and neural circuits of neuropsychiatric symptoms (NPS) in patients with Alzheimer's disease (AD) is expensive and usually invasive, limiting its use in clinical practice. OBJECTIVE: To investigate the cerebral morphology and perfusion characteristics of NPS and identify the spatiotemporal perfusion circuits of NPS sub-symptoms. METHODS: This nested case-control study included 102 AD patients with NPS and 51 age- and sex-matched AD patients without NPS. Gray matter volume, cerebral blood flow (CBF), and arterial transit time (ATT) were measured and generated using time-encoded 7-delay pseudo-continuous arterial spin labeling (pCASL). Multiple conditional logistic regression analysis was used to identify neuroimaging markers of NPS. The associations between the CBF or ATT of affected brain areas and NPS sub-symptoms were evaluated after adjusting for confounding factors. The neural circuits of sub-symptoms were identified based on spatiotemporal perfusion sequencing. RESULTS: Lower Mini-Mental State Examination scores (p < 0.001), higher Caregiver Burden Inventory scores (p < 0.001), and higher CBF (p = 0.001) and ATT values (p < 0.003) of the right anteroventral thalamic nucleus (ATN) were risk factors for NPS in patients with AD. Six spatiotemporal perfusion circuits were found from 12 sub-symptoms, including the anterior cingulate gyri-temporal pole/subcortical thalamus-cerebellum circuit, insula-limbic-cortex circuit, subcortical thalamus-temporal pole-cortex circuit, subcortical thalamus-cerebellum circuit, frontal cortex-cerebellum-occipital cortex circuit, and subcortical thalamus-hippocampus-dorsal raphe nucleus circuit. CONCLUSIONS: Prolonged ATT and increased CBF of the right ATN may be neuroimaging markers for detecting NPS in patients with AD. Time-encoded pCASL could be a reliable technique to explore the neural perfusional circuits of NPS.

Hedge transfer learning routing for dynamic searching and reconnoitering applications in 3D multimedia FANETs.

With the fast development of unmanned aerial vehicles (UAVs) and the user increasing demand of UAV video transmission, UAV video service is widely used in dynamic searching and reconnoitering applications. Video transmissions not only consider the complexity and instability of 3D UAV network topology but also ensure reliable quality of service (QoS) in flying ad hoc networks (FANETs). We propose hedge transfer learning routing (HTLR) for dynamic searching and reconnoitering applications to address this problem. Compared with the previous transfer learning framework, HTRL has the following innovations. First, hedge principle is introduced into transfer learning. Online model is continuously trained on the basis of offline model, and their weight factors are adjusted in real-time by transfer learning, so as to adapt to the complex 3D FANETs. Secondly, distributed multi-hop link state scheme is used to estimate multi-hop link states in the whole network, thus enhancing the stability of transmission links. Among them, we propose the multiplication rule of multi-hop link states, which is a new idea to evaluate link states. Finally, we use packet delivery rate (PDR) and energy efficiency rate (EER) as two main evaluation metrics. In the same NS3 experimental scenario, the PDR of HTLR is at least 5.11% higher and the EER is at least 1.17 lower than compared protocols. Besides, we use Wilcoxon test to compare HTLR with the simplified version of HTLR without hedge transfer learning (N-HTLR). The results show that HTRL is superior to N-HTRL, effectively ensuring QoS.

Patient Acceptability of Symptom Screening and Patient Education Using a Chatbot for Autoimmune Inflammatory Diseases: Survey Study.

BACKGROUND: Chatbots have the potential to enhance health care interaction, satisfaction, and service delivery. However, data regarding their acceptance across diverse patient populations are limited. In-depth studies on the reception of chatbots by patients with chronic autoimmune inflammatory diseases are lacking, although such studies are vital for facilitating the effective integration of chatbots in rheumatology care. OBJECTIVE: We aim to assess patient perceptions and acceptance of a chatbot designed for autoimmune inflammatory rheumatic diseases (AIIRDs). METHODS: We administered a comprehensive survey in an outpatient setting at a top-tier rheumatology referral center. The target cohort included patients who interacted with a chatbot explicitly tailored to facilitate diagnosis and obtain information on AIIRDs. Following the RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework, the survey was designed to gauge the effectiveness, user acceptability, and implementation of the chatbot. RESULTS: Between June and October 2022, we received survey responses from 200 patients, with an equal number of 100 initial consultations and 100 follow-up (FU) visits. The mean scores on a 5-point acceptability scale ranged from 4.01 (SD 0.63) to 4.41 (SD 0.54), indicating consistently high ratings across the different aspects of chatbot performance. Multivariate regression analysis indicated that having a FU visit was significantly associated with a greater willingness to reuse the chatbot for symptom determination (P=.01). Further, patients' comfort with chatbot diagnosis increased significantly after meeting physicians (P<.001). We observed no significant differences in chatbot acceptance according to sex, education level, or diagnosis category. CONCLUSIONS: This study underscores that chatbots tailored to AIIRDs have a favorable reception. The inclination of FU patients to engage with the chatbot signifies the possible influence of past clinical encounters and physician affirmation on its use. Although further exploration is required to refine their integration, the prevalent positive perceptions suggest that chatbots have the potential to strengthen the bridge between patients and health care providers, thus enhancing the delivery of rheumatology care to various cohorts.

Role of Berberine Thermosensitive Hydrogel in Periodontitis via PI3K/AKT Pathway In Vitro.

Periodontitis is a long-term inflammatory illness and a leading contributor to tooth loss in humans. Due to the influence of the anatomic parameters of teeth, such as root bifurcation lesions and the depth of the periodontal pocket, basic periodontal treatment on its own often does not completely obliterate flora microorganisms. As a consequence, topical medication has become a significant supplement in the treatment of chronic periodontitis. Berberine (BBR) has various pharmacological effects, such as hypoglycemic, antitumor, antiarrhythmic, anti-inflammatory, etc. The target of our project is to develop a safe and non-toxic carrier that can effectively release berberine, which can significantly reduce periodontal tissue inflammation, and to investigate whether berberine thermosensitive hydrogel can exert anti-inflammatory and osteogenic effects by modulating phosphatifylinositol-3-kinase/Protein Kinase B (PI3K/AKT) signaling pathway. Consequently, firstly berberine temperature-sensitive hydrogel was prepared, and its characterizations showed that the mixed solution gelated within 3 min under 37 °C with a hole diameter of 10-130 µm, and the accumulation of berberine release amounted to 89.99% at 21 days. CCK-8 and live-dead cell staining results indicated that this hydrogel was not biotoxic, and it is also presumed that the optimum concentration of berberine is 5 µM, which was selected for subsequent experiments. Real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB)results demonstrated that inflammatory factors, as well as protein levels, were significantly reduced in the berberine-loaded hydrogel group, and LY294002 (PI3K inhibitor) could enhance this effect (p < 0.05). In the berberine-loaded hydrogel group, osteogenesis-related factor levels and protein profiles were visibly increased, along with an increase in alkaline phosphatase expression, which was inhibited by LY294002 (p < 0.05). Therefore, berberine thermosensitive hydrogel may be an effective treatment for periodontitis, and it may exert anti-inflammatory and osteogenic effects through the PI3K/AKT signaling pathway.

Nutrition in Alzheimer's disease: a review of an underappreciated pathophysiological mechanism.

Alzheimer's disease (AD) is the leading cause of dementia in older individuals and is an escalating challenge to global public health. Pharmacy therapy of AD is one of the well-funded areas; however, little progress has been made due to the complex pathogenesis. Recent evidence has demonstrated that modifying risk factors and lifestyle may prevent or delay the incidence of AD by 40%, which suggests that the management should pivot from single pharmacotherapy toward a multipronged approach because AD is a complex and multifaceted disease. Recently, the gut-microbiota-brain axis has gained tremendous traction in the pathogenesis of AD through bidirectional communication with multiple neural, immune, and metabolic pathways, providing new insights into novel therapeutic strategies. Dietary nutrition is an important and profound environmental factor that influences the composition and function of the microbiota. The Nutrition for Dementia Prevention Working Group recently found that dietary nutrition can affect cognition in AD-related dementia directly or indirectly through complex interactions of behavioral, genetic, systemic, and brain factors. Thus, considering the multiple etiologies of AD, nutrition represents a multidimensional factor that has a profound effect on AD onset and development. However, mechanistically, the effect of nutrition on AD is uncertain; therefore, optimal strategies or the timing of nutritional intervention to prevent or treat AD has not been established.Thus, this review summarizes the current state of knowledge concerning nutritional disorders, AD patient and caregiver burden, and the roles of nutrition in the pathophysiology of AD. We aim to emphasize knowledge gaps to provide direction for future research and to establish optimal nutrition-based intervention strategies for AD.

A Multifunctional Dental Resin Composite with Sr-N-Doped TiO2 and n-HA Fillers for Antibacterial and Mineralization Effects.

Dental caries, particularly secondary caries, which is the main contributor to dental repair failure, has been the subject of extensive research due to its biofilm-mediated, sugar-driven, multifactorial, and dynamic characteristics. The clinical utility of restorations is improved by cleaning bacteria nearby and remineralizing marginal crevices. In this study, a novel multifunctional dental resin composite (DRC) composed of Sr-N-co-doped titanium dioxide (Sr-N-TiO2) nanoparticles and nano-hydroxyapatite (n-HA) reinforcing fillers with improved antibacterial and mineralization properties is proposed. The experimental results showed that the anatase-phase Sr-N-TiO2 nanoparticles were synthesized successfully. After this, the curing depth (CD) of the DRC was measured from 4.36 ± 0.18 mm to 5.10 ± 0.19 mm, which met the clinical treatment needs. The maximum antibacterial rate against Streptococcus mutans (S. mutans) was 98.96%, showing significant inhibition effects (p < 0.0001), which was experimentally verified to be derived from reactive oxygen species (ROS). Meanwhile, the resin exhibited excellent self-remineralization behavior in an SBF solution, and the molar ratio of Ca/P was close to that of HA. Moreover, the relative growth rate (RGR) of mouse fibroblast L929 indicated a high biocompatibility, with the cytotoxicity level being 0 or I. Therefore, our research provides a suitable approach for improving the antibacterial and mineralization properties of DRCs.

A Self-Supplying H2O2 Modified Nanozyme-Loaded Hydrogel for Root Canal Biofilm Eradication.

The success of root canal therapy depends mainly on the complete elimination of the root canal bacterial biofilm. The validity and biocompatibility of root canal disinfectant materials are imperative for the success of root canal treatment. However, the insufficiency of the currently available root canal disinfectant materials highlights that more advanced materials are still needed. In this study, a nanozyme-loaded hydrogel (Fe3O4-CaO2-Hydrogel) was modified and analyzed as a root canal disinfectant material. Fe3O4-CaO2-Hydrogel was fabricated and examined for its release profile, biocompatibility, and antibacterial activity against E. faecalis and S. sanguis biofilms in vitro. Furthermore, its efficiency in eliminating the root canal bacterial biofilm removal in SD rat teeth was also evaluated. The results in vitro showed that Fe3O4-CaO2-Hydrogel could release reactive oxygen species (ROS). Moreover, it showed good biocompatibility, disrupting bacterial cell membranes, and inhibiting exopolysaccharide production (p < 0.0001). In addition, in vivo results showed that Fe3O4-CaO2-Hydrogel strongly scavenged on root canal biofilm infection and prevented further inflammation expansion (p < 0.05). Altogether, suggesting that Fe3O4-CaO2-Hydrogel can be used as a new effective biocompatible root canal disinfectant material. Our research provides a broad prospect for clinical root canal disinfection, even extended to other refractory infections in deep sites.

The characteristics of arterial spin labeling cerebral blood flow in patients with subjective cognitive decline: The Chinese imaging, biomarkers, and lifestyle study.

Objective: We aimed to characterize the potential risk factors and cerebral perfusion of patients with subjective cognitive decline (SCD). Methods: This prospective study enrolled consecutive patients from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) Cohort of Alzheimer's disease between February 2021 and March 2022. Patients who met the SCD diagnostic criteria were categorized into the SCD group, while those without cognitive complaints or any concerns were assigned to the healthy control (HC) group. The demographic and clinical characteristics and cerebral blood flow (CBF) from pseudo-continuous arterial spin labeling (pCASL) in standard cognitive regions were compared between these two groups. A multivariate analysis was performed to identify independent factors associated with SCD. Results: The frequency of family history of dementia in the SCD group was higher compared with the HC group (p = 0.016). The CBF of left hippocampus (p = 0.023), left parahippocampal gyrus (p = 0.004), left precuneus (p = 0.029), left middle temporal gyrus (p = 0.022), right parahippocampal gyrus (p = 0.018), and right precuneus (p = 0.024) in the SCD group were significantly increased than those in the HC group. The multivariate logistic regression analyses demonstrated that the family history of dementia [OR = 4.284 (1.096-16.747), p = 0.036] and the CBF of left parahippocampal gyrus [OR = 1.361 (1.006-1.840), p = 0.045] were independently associated with SCD. Conclusion: This study demonstrated that the family history of dementia and the higher CBF within the left parahippocampal gyrus were independent risk factors associated with patients with SCD, which could help in the early identification of the SCD and in intervening during this optimal period.

Posterior circulation stroke due to intracranial artery disease in the Chinese population.

BACKGROUND: Little is known about the distribution of the intracranial arteries that are responsible for noncardiogenic posterior circulation stroke (PCS) in the Chinese population. Furthermore, few studies have compared the imaging manifestations and outcomes across PCS due to the disease of different intracranial arteries. Therefore, our aim was to demonstrate the distribution of the intracranial arteries that were responsible for noncardiogenic PCS and to compare the imaging manifestations and outcome across PCS due to the disease of different intracranial arteries. METHODS: We prospectively enrolled 690 patients from 22 Chinese centers with noncardiogenic PCS due to intracranial artery disease. Intracranial artery disease was classified as intracranial vertebral artery disease (IVAD) and intracranial nonvertebral artery disease (INVAD). Clinical-radiologic patterns and outcomes were compared between IVAD and INVAD. RESULTS: INVAD was more frequent than IVAD. Compared to the INVAD group, the IVAD group more frequently had hypertension, coronary heart disease, multiple infarcts, border zone infarcts, territorial infarcts, small cortical infarcts, multilevel infarcts, multisector infarcts, and more often had severe stenosis of the responsible artery, more often presented with decreased alertness, gaze palsy, bilateral limb weakness, ataxia, dysphagia, diplopia, vertigo, and headache. In addition, the IVAD group had a higher National Institutes of Health stroke scale score and modified Rankin Scale score at discharge and more deaths and recurrent ischemic cerebrovascular disease within 1 year of onset. Multivariable Cox regression identified IVAD as an independent predictor of recurrent ischemic cerebrovascular disease. CONCLUSIONS: PCS due to INVAD was more common in the Chinese population. However, PCS due to IVAD had more serious clinical-radiologic patterns and worse outcomes.

The role of hypertension and diabetes mellitus on the etiology of middle cerebral artery disease.

BACKGROUND: Ischemic stroke (IS) caused by middle cerebral artery (MCA) disease is the most common type of IS caused by intracranial artery disease in the Chinese population. Hypertension and diabetes mellitus are the common risk factors of cerebral small vessel disease and large artery atherosclerosis (LAA). However, little is known about whether hypertension and diabetes mellitus had different correlations with the small artery occlusion (SAO) and LAA etiology of MCA disease. Therefore, our aim was to identify the predictors of the etiology of MCA disease. METHODS: We consecutively enrolled 967 patients with noncardiogenic IS in unilateral MCA territory. Vascular risk factors and the clinical-radiologic features of IS were analyzed. The etiology of IS were classified as SAO or LAA according to the Stop Stroke Study Trial of Org 10172 in Acute Stroke Treatment classification criteria. Multivariable logistic regression was used to identify the differences in the predictors between SAO and LAA etiology of MCA disease. RESULTS: Multivariable logistic regression identified male and hypertension as the predictors of the SAO etiology of MCA disease, however diabetes mellitus, repeated transient ischemic attack before the stroke, gaze palsy, aphasia, headache at admission, and disability at discharge as the predictors of the LAA etiology of MCA disease. CONCLUSION: Hypertension and diabetes mellitus are related with the different etiology of MCA disease.

Posterior circulation stroke due to vertebral artery disease in the Chinese population.

BACKGROUND AND PURPOSE: Little is known about the distribution of the arteries responsible for noncardiogenic posterior circulation stroke due to vertebral artery disease in the Chinese population. Furthermore, few studies have compared the risk factors, imaging manifestations, and outcomes across different types of vertebral artery disease. Therefore, our aim was to compare the differences in the risk factors, imaging manifestations, and outcome across various types of vertebral artery disease. METHODS: We prospectively enrolled 228 patients from 22 Chinese centers with noncardiogenic posterior circulation stroke due to vertebral artery disease. Vertebral artery disease was classified by the involved segments of the responsible vertebral artery, and basilar artery (BA) involvement or not. Risk factors, clinical-radiologic patterns, and outcomes were compared across different types of vertebral artery disease. RESULTS: The intracranial vertebral artery (ICVA) was more frequently involved than was the extracranial vertebral artery (ECVA). The ICVA/ICVA + ECVA group more often presented with hypertension and higher systolic blood pressure than did the ECVA group. Compared with the single-segment-of-vertebral-artery group (SSVA), the group with multiple-segments-of-vertebral-artery (MSVA) involvement or SSVA with BA involvement had more serious clinical-radiologic patterns and worse outcomes. Multivariable Cox regression identified MSVA/SSVA + BA involvement as an independent predictor of recurrent ischemic cerebrovascular events. CONCLUSIONS: The risk factors for ICVA/ICVA + ECVA were different from those of ECVA, and the MSVA/SSVA + BA group had more serious clinical-radiologic patterns and worse outcomes.

Anti-inflammatory effect of IL-1ra-loaded dextran/PLGA microspheres on Porphyromonas gingivalis lipopolysaccharide-stimulated macrophages in vitro and in vivo in a rat model of periodontitis.

Periodontitis is a multifactorial chronic infectious disease leading to a host immune response involving inflammatory cytokines, especially IL-1ß, which is the main reason for further developing this disease. IL-1 receptor antagonist (IL-1ra) binds IL-1 receptor, inhibiting IL-1ß signaling and reducing the levels of other cytokines closely related to periodontitis, such as IL-6 and TNF-α. Therefore, the use of IL-1ra to inhibit periodontitis development in a system, ensuring its sustained release, might be an effective way to combat this disease. Hence, in this study, a novel IL-1ra-loaded dextran/PLGA microsphere was developed to allow the sustained release of IL-1ra and enhance the anti-inflammatory properties. Therefore, this study's purposes were to develop a novel periodontal treatment for inhibition and treatment of periodontitis and evaluate the sustained-release effect and anti-inflammatory properties of IL-1ra-loaded dextran/PLGA microspheres in vitro by cell experiments and in vivo by animal experiments. The results showed that IL-1ra-loaded dextran/PLGA microspheres were non-toxic both in vitro and in vivo and could be used as a safe and effective treatment. In addition, these microspheres could significantly prolong the half-life of IL-1ra drug, exerting a useful anti-inflammatory effect in macrophages stimulated with P. gingivalis lipopolysaccharide and in rats with periodontitis. In conclusion, IL-1ra-loaded dextran/PLGA microsphere might be a useful tool to combat periodontal disease.

Plaque morphology in acute symptomatic intracranial atherosclerotic disease.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is globally a major ischaemic stroke subtype with high recurrence. Understanding the morphology of symptomatic ICAD plaques, largely unknown by far, may help identify vulnerable lesions prone to relapse. METHODS: We prospectively recruited patients with acute ischaemic stroke or transient ischaemic attack attributed to high-grade ICAD (60%-99% stenosis). Plaque morphological parameters were assessed in three-dimensional rotational angiography, including surface contour, luminal stenosis, plaque length/thickness, upstream shoulder angulation, axial/longitudinal plaque distribution and presence of adjoining branch atheromatous disease (BAD). We compared morphological features of smooth, irregular and ulcerative plaques and correlated them with cerebral ischaemic lesion load downstream in MRI. RESULTS: Among 180 recruited patients (median age=60 years; 63.3% male; median stenosis=75%), plaque contour was smooth (51 (28.3%)), irregular (101 (56.1%)) or ulcerative (28 (15.6%)). Surface ulcers were mostly at proximal (46.4%) and middle one-third (35.7%) of the lesions. Most (84.4%) plaques were eccentric, and half had their maximum thickness over the distal end. Ulcerative lesions were thicker (medians 1.6 vs 1.3 mm; p=0.003), had steeper upstream shoulder angulation (56.2° vs 31.0°; p<0.001) and more adjoining BAD (83.3% vs 57.0%; p=0.033) than non-ulcerative plaques. Ulcerative plaques were significantly associated with coexisting acute and chronic infarcts downstream (35.7% vs 12.5%; adjusted OR 4.29, 95% CI 1.65 to 11.14, p=0.003). Sensitivity analyses in patients with anterior-circulation ICAD lesions showed similar results in the associations between the plaque types and infarct load. CONCLUSIONS: Ulcerative intracranial atherosclerotic plaques were associated with vulnerable morphological features and had a higher cumulative infarct load downstream.