Loss of ß-arrestin2 aggravated condylar cartilage degeneration at the early stage of temporomandibular joint osteoarthritis.

OBJECTIVE: Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative joint disorder characterized by extracellular matrix degeneration and inflammatory response of condylar cartilage. ß-arrestin2 is an important regulator of inflammation response, while its role in TMJOA remains unknown. The objective of this study was to investigate the role of ß-arrestin2 in the development of TMJOA at the early stage and the underlying mechanism. METHODS: A unilateral anterior crossbite (UAC) model was established on eight-week-old wild-type (WT) and ß-arrestin2 deficiency mice to simulate the progression of TMJOA. Hematoxylin-eosin (HE) staining and microcomputed tomography (micro-CT) analysis were used for histological and radiographic assessment. Immunohistochemistry was performed to detect the expression of inflammatory and degradative cytokines, as well as autophagy related factors. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay was carried out to assess chondrocyte apoptosis. RESULTS: The loss of ß-arrestin2 aggravated cartilage degeneration and subchondral bone destruction in the model of TMJOA at the early stage. Furthermore, in UAC groups, the expressions of degradative (Col-X) and inflammatory (TNF-α and IL-1ß) factors in condylar cartilage were increased in ß-arrestin2 null mice compared with WT mice. Moreover, the loss of ß-arrestin2 promoted apoptosis and autophagic process of chondrocytes at the early stage of TMJOA. CONCLUSION: In conclusion, we demonstrated for the first time that ß-arrestin2 plays a protective role in the development of TMJOA at the early stage, probably by inhibiting apoptosis and autophagic process of chondrocytes. Therefore, ß-arrestin2 might be a potential therapeutic target for TMJOA, providing a new insight for the treatment of TMJOA at the early stage.

Sleep and mental health among Chinese adolescents: the chain-mediating role of physical health perception and school adjustment.

OBJECTIVE: Sleep problems and their detrimental effects on adolescents' physical and mental health have received substantial attention. Prior studies have focused mainly on the direct association between sleep and mental health; however, little is known about the underlying mediating mechanism. To address this gap, the present study constructed a chain mediation model to examine the association between sleep deficiency and mental health status in adolescents, by introducing two mediating variables-physical health perception and school adjustment. METHODS: A sample of 7530 senior high school students completed a battery of self-report questionnaires measuring their sleep duration, mental health status, physical health perception, and school adjustment. Data were collected from the Database of Youth Health at Shandong University. All the measures showed good reliability and validity in the present study. Data were analyzed using SPSS 25.0 and the SPSS PROCESS. RESULTS: The results were as follows: (1) Sleep duration was significantly associated with physical health perception and mental health. (2) Physical health perception partially mediated the association between sleep and mental health. (3) Physical health perception and school adjustment played a chain mediating role between sleep and mental health. In conclusion, sleep not only directly associated with mental health among adolescents, but also influences mental health by the chain mediating effect of perception of physical health and school adjustment. CONCLUSION: These findings in the present study contribute to understanding the mechanisms underlying the association between sleep and mental health and have important implications for interventions aimed at improving mental health status among adolescents in China. Our results indicated that promoting adequate sleep duration and improving sleep quality are possible key mental health promotion strategies for adolescents.

Determinants of behavioral intentions to use E-Pharmacy service: Insights from TAM theory and the moderating influence of technological literacy.

BACKGROUND: The growing significance of E-Pharmacy services in healthcare necessitates investigating the factors influencing users' behavioral intentions on these platforms. Comprehending these variables is imperative to maximize service provision, elevate customer satisfaction, and ultimately elevate healthcare accessibility and results. OBJECTIVE(S): The main goal of this study is to explore the factors that shape consumers' inclination to use E-Pharmacy services, focusing on the framework provided by the Technology Acceptance Model. Additionally, we aimed to investigate how technological literacy plays a moderating role in this context, specifically within the South African setting. METHODS: Using a sample of 480 South African clients, the Technology Acceptance Model (TAM) and partial least squares structural equation modeling (PLS-SEM) were used to investigate the factors influencing behavioral intention to use E-Pharmacy services. RESULTS: The findings underscore perceived usefulness, trust, performance expectancy, and social Influence as fundamental drivers influencing users' intentions to adopt E-Pharmacy systems. Additionally, the study shows that consumers' intention to use E-Pharmacy services is significantly and favorably affected by their desire to utilize such services. This suggests that individuals are more likely to act on positive intentions when they are interested in using E-Pharmacy platforms. Intriguingly, technological literacy has emerged as a moderating factor in the relationship between the intention to use and the actual behavior of utilizing E-Pharmacy platforms. This demonstrates the importance of consumers' technical knowledge and skills in bridging the intention-behavior gap and highlights the necessity of adapting treatments and instructional strategies to account for various levels of technological literacy. CONCLUSION: This study provides valuable insights into the complex relationships between factors influencing the acceptance of E-Pharmacy services in South Africa. This knowledge can have practical implications for lawmakers, developers of E-Pharmacy platforms, and healthcare professionals who aim to enhance user acceptance and utilization.

Quality appraisal of clinical practice guidelines addressing massage interventions using the AGREE II instrument.

OBJECTIVE: The purpose of this study was to systematically evaluate the methodological quality of massage-related clinical practice guidelines (CPGs)/consensus on massage using the Appraisal of Guidelines Research and Evaluation (AGREE II) instrument and to summarize the current status of recommendations in the CPGs. METHODS: The Chinese National Knowledge Infrastructure (CNKI), WanFang Data, China Science and Technology Journal Database (VIP), China Biology Medicine disc (CBM), PubMed, Embase, and guideline websites (such as the Chinese Medical Ace Base, the China Association of Chinese Medicine, the World Health Organization, Guideline International Network, National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network) were searched from inception to October 31, 2022. In addition, the reference lists of relevant studies were reviewed to identify domestic and overseas massage CPGs/consensus. The search terms adopted a combination of subject words and free words, mainly including traditional Chinese medicine, complementary therapies, Tuina, massage, manipulation, chiropractic/osteopathic, spinal, acupressure, guideline, and consensus. Two researchers independently completed the eligible records and extracted the data. Before the formal research, calibrations were performed twice on AGREE II, and all reviewers completed the pilot test three times until they understood and reached an agreement on the assessment items. Three researchers appraised the methodological quality of the included guidelines using the AGREE II instrument and calculated the overall intraclass correlation coefficient (ICC) of agreement. RESULTS: The evaluation results showed that among the 49 eligible CPGs/consensus, 4 (8.2%) CPGs/consensus were considered "recommended", 15 (30.6%) CPGs/consensus were considered "recommended with modifications", and 30 (61.2%) CPGs/consensus were considered "not recommended", while the consensus was considered "not recommended". Generally, the scores in the six domains of the guidelines were all higher than the consensus. Evaluation results for the overall quality of 36 CPGs showed that 4 (11%) were "good quality", 15 (42%) were "sufficient quality" and 17 (47%) were "lower quality". The AGREE II quality scores of domains ranged from 0.30 to 0.75 ([ICC = 0.993, 95% CI (0.992, 0.995)]). The domain of scope and purpose (domain 1), with a median score of 0.75 (0.52~0.91), performed best in the guidelines with AGREE II, and stakeholder involvement (domain 2) [median 0.39 (0.31~0.56)] and application (domain 5) [median 0.30 (0.17~0.47] obtained lower scores. The consensus score of domain 1 was better at 26.0 (21.6~44.8), followed by rigor of development (domain 3) with a score of 18.0 (10.0~28.9). A total of 119 massage-related recommendations were extracted from 49 guidelines/consensuses, including "in favor" (102, 85.7%), "against" (9, 7.6%), and "did not make recommendations" (8, 6.7%). CONCLUSION: The overall quality of the included guidelines was low, and most of the guidelines were not "recommended". In future guideline updates, the existing evidence should be used, the professional composition of members of the expert group should be enriched, and patients' values and preferences should be fully considered. It is necessary to clearly propose recognizable recommendations and strengthen the rigor and standardization of guideline formulation. Thus, clear standard guidelines can be formulated to better guide clinical practice.

Multiple Lung Cavity Lesions, Thoracic Wall Abscess and Vertebral Destruction Caused by Streptococcus constellatus Infection: A Case Report.

Disseminated infection caused by Streptococcus constellatus was seldom occurred. We reported a case of Streptococcus constellatus infection, presenting as multiple pulmonary cavities, thoracic wall abscess and vertebral destruction. The 37-year-old male had recurrent fever, chest wall swelling and pain, and lower limb numbness, he had weak physical condition and previously suffered from poorly controlled diabetes and severe periodontal disease for 3 years. Definite diagnosis of Streptococcus constellatus infection was made by metagenomic next­generation sequencing (mNGS) in abscess drainage fluid. Systemic antibiotics and thoracic wall drainage were given, and the pulmonary cavity and the thoracic intermuscular abscess were significantly decreased. Few to no study reported the disseminated infection (pulmonary cavities, thoracic wall abscess and vertebral destruction) caused by Streptococcus constellatus. This case report highlighted the importance of mNGS for accurate diagnosis, as well as the timely drainage and antibiotics for effective treatment of Streptococcus constellatus infection.

Airway morphological abnormalities of bronchiolitis assessed by endobronchial optical coherence tomography.

BACKGROUND: A few studies have reported the medium-sized and small airway morphological abnormalities of bronchiolitis. Whether spirometry or impulse oscillometry (IOS) is correlated with airway remodeling of bronchiolitis remains unclear. OBJECTIVES: Aiming to demonstrate the airway morphological abnormalities of bronchiolitis obliterans (BO) and diffuse panbronchiolitis (DPB) assessed by endobronchial optical coherence tomography (EB-OCT), and elucidate whether spirometric and IOS parameters have correlation with the airway remodeling of bronchiolitis. METHODS: We recruited 18 patients with bronchiolitis (BO, n = 9; DPB, n = 9) and 17 control subjects. Assessments of clinical features, St. George's respiratory questionnaire (SGRQ), chest computed tomography (CT), spirometry, IOS, and EB-OCT were performed in all enrolled subjects. The correlation between EB-OCT and lung function parameters was studied and analyzed. RESULTS: The magnitude of abnormalities of spirometric and IOS parameters was significantly greater in patients with bronchiolitis than that in control subjects (p < 0.05). Patients with BO had notably lower forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, maximal mid-expiratory flow (MMEF)% pred and higher resonant frequency (Fres), and area of reactance (AX) than those with DPB (p < 0.05). The EB-OCT measurement among patients with bronchiolitis and between the bronchus in the left and the right lung demonstrated a heterogeneous distribution of airway calibers, presenting a high intra- and inter-individual variability. Patients with bronchiolitis had notably greater airway wall area (p < 0.05) compared with control, while BO presented greater magnitude of airway abnormalities than DPB. Fres and the difference in airway resistance at 5 and 20 Hz (R5-R20) correlated negatively with medium-sized and small airway inner area, and correlated positively with airway wall area (p < 0.05), whose correlation coefficients were higher than those of spirometric parameters. CONCLUSION: Bronchiolitis, BO and DPB, manifested a heterogeneous distribution of airway calibers with significant intra- and inter-individual variability. IOS parameters, rather than spirometry, correlated better with medium-sized and small airway remodeling in bronchiolitis assessed by EB-OCT measurement.

Bilateral medial medullary infarction with intravenous thrombolytic therapy: A case report.

RATIONALE: Bilateral medial medullary infarction is a rare stroke subtype. To investigate its clinical manifestations, etiology, imaging features and thrombolytic effect, We here in reported a patient with acute ischemic stroke in the bilateral medial medullary and reviewed the related literatures. PATIENTS CONCERN: A 64-year-old female was taken to our hospital after 4.5 hours of dizziness in the morning, followed by somnolence and limb weakness. She gradually worsened into a rapidly progressive tetraparesis and slurred speech. DIAGNOSES: Diffusion weighted imaging exhibited a "heart appearance" sign in bilateral medial medulla oblongata, and high-resolution magnetic resonance imaging suggested the left vertebral artery-4 thromboembolism. INTERVENTIONS: Timely intravenous thrombolysis was performed. OUTCOME: After intravenous thrombolysis, the patient's symptoms did not worsen in a short time. Although the symptoms were aggravated in the later stage, they were alleviated after active treatment. LESSONS: Diffusion weighted imaging can assist in the early diagnosis of bilateral medial medullary infarction, which will help in the decision to proceed with intravenous thrombolysis therapy. High-resolution magnetic resonance imaging should be improved as soon as possible, which can provide basis for the next intravascular interventional therapy.

[λ approach for the repairment of large skin defects after resection of preauricular fistula with cellulitis in children].

Objective:To explore the feasibility and advantages of λ approach for the repairment of large skin defects after resection of preauricular fistula with cellulitis in children. Methods:The clinical data of patients with preauricular fistula with cellulitis treated by λ approach from January 2016 to January 2021 were analyzed retrospectively. Results:After follow-up for 10-18 months, the primary healing rate of incision was 97.8%, and the survival rate of λ flap was 100%. Conclusion:λ approach is a safe, effective and cosmetic method. It can be used to repair the large skin defects after resection of preauricular fistula with cellulitis in children.

[Hyoid body morphology of thyroglossal duct cyst: a comparative study based on imaging].

Objective:To provide reference for preoperative diagnosis and treatment of thyroglossal duct cyst by studying the morphological changes of hyoid body. Methods:The CT data（midsagittal image） of congenital thyroglossal duct cyst（TGDC group） diagnosed by pathology and the control group（C group） were collected from January 2016 to October 2021. The differences of hyoid body height（HBH）, hyoid body width（HBW）, hyoid bone thickness（HBT）, HBW/HBH, HBT/HBH between the two groups were compared. HBH, HBW and HBT were analyzed by t-test; The HBW/HBH and HBT/HBH were analyzed by Mann-Whitney U test. Results:Twenty-nine cases were included in the TGDC group and 58 in the C group. The HBH in the TGDC group was（8.93 ±0.22） mm and that in the C group was（8.94±0.12） mm, there was no significant difference between the two groups（P>0.05）. The HBW in the TGDC group and the C group were（5.09±0.21） mm and（4.48±0.11） mm, and the HBT were（3.84±0.12） mm and（3.13±0.08） mm, respectively, the difference between the two groups was statistically significant（P<0.05）. The average rank sum of HBW/HBH in the TGDC group and the C group was 53.95 and 39.03, respectively, and the average rank sum of HBT/HBH was 59.90 and 36.05, respectively, the difference between the two groups was statistically significant（P<0.05）. Conclusion:The morphological changes of hyoid body of thyroglossal duct cyst may be helpful for preoperative diagnosis, and it also suggests that hyoid body resection may reduce the possibility of postoperative recurrence.

The General Public Knowledge, Attitude, and Practices Regarding COVID-19 During the Lockdown in Asian Developing Countries.

The recent outbreak of coronavirus disease (COVID-19) is the worst global crisis. Since no successful treatment and vaccine have been reported, efforts to improve the public's knowledge, attitudes, and practices are critical to reducing the spread of COVID-19. This study aims to investigate the general public knowledge, attitude, and practices regarding COVID-19. A cross-sectional online survey was conducted in three developing countries (China, India, and Pakistan). The reason for choosing only three countries is to identify the cross-border effect statistically and data collection constraints. The IBM SPSS version 23.0 was used for descriptive, univariate, and multivariate analysis of the study. One thousand one hundred and sixty participants completed the study, one-quarter of them were female, and three-quarters were male. The study's findings evidenced that the knowledge and attitude correlation was 58.4% and between knowledge and practices 18.2%. Furthermore, the knowledge was found lower in females, among India and Pakistan, and people aged less and equivalent to 30 years. The attitudes among respondents were found poorer among unmarried females and India and Pakistan residents. While the practices found lower among employed, unemployed and, respondents had a bachelor's degree, and females reside in India. And future studies should focus on factors that influence the government regarding the imposition of lockdown, boost the economy in the pandemic, and motivate the general public to follow the health institution's instructions.

Photophyical and photosensitizing properties of BODIPYs substantially changed by alkyl- and phenyl-amino groups on meso carbon.

meso-RNH (R = C3H7, C4H9, PhCH2, H, and Ph) substituted BODIPY compounds have been prepared to examine their photophysical properties and photosensitizing abilities. We have measured the UV-vis absorption, steady state and time resolved fluorescence, excited triplet state formation using laser flash photolysis, singlet oxygen generation ability using chemical trapping method. The results show that the presence of meso-RNH leads to large blue shift of absorption and emission wavelength, remarkable decrease in fluorescence quantum yield and lifetime values, and significant increase in singlet oxygen formation quantum yield. Quantum chemical calculation also reveals the photoinduced charge transfer (PCT) mechanism. We conclude that property changes are due to: 1) S0 and S1 geometry, 2) ground state structural isomerization, and 3) intramolecular PCT. These results and mechanisms are helpful for designing new functional materials.

NFIC1 inhibits the migration and invasion of MDA-MB-231 cells through S100A2-mediated inactivation of MEK/ERK pathway.

NFIC is a potent transcriptional factor involved in many physiological and pathological processes, including tumorigenesis. However, the role of NFIC1, the longest isoform of NFIC, in the progression of triple negative breast cancer (TNBC) remains elusive. Our study demonstrates that overexpression of NFIC1 inhibits the migration and invasion of TNBC MDA-MB-231 cells. NFIC1 regulates the expression of S100A2, and knockdown of S100A2 reverses the inhibitive effects of NFIC1 on the migration and invasion of MDA-MB-231 cells. Furthermore, knockdown of S100A2 activates the MEK/ERK signaling transduction pathway that is inhibited by NFIC1 overexperssion. Treatment with MEK/ERK pathway inhibitor, U0126, abolishes the effects of S100A2 knockdown. In addition, overexpression of NFIC1 in MDA-MB-231 cells increases the expression of epithelial markers and decreases the expression of mesenchymal markers, and these effects could also be reversed by knockdown of S100A2. Collectively, these results demonstrate that NFIC1 inhibits the Epithelial-mesenchymal transition (EMT) of MDA-MB-231 cells by regulating S100A2 expression, which suppress the activation of MEK/ERK pathway. Therefore, our study confirms the role of NFIC1 as a tumor repressor in TNBC, and reveals the molecular mechanism through which NFIC1 inhibits the migration and invasion of MDA-MB-231 cells.

Employee performance under transformational leadership and organizational citizenship behavior: A mediated model.

Globally, small and medium-sized enterprises (SMEs) compete and work on their sustainability in order to survive and thrive. SMEs rely only on their internal strength, and this strength lies mainly in their employees. Maintaining employees and their engagement increases productivity not only in terms of employee performance but also in terms of organizational performance. Based on social bond theory, the link between leaders and employees empowers the employees; in this context, the present research addresses how SMEs' potential effectiveness is derived from the employees when leadership plays its role efficiently and promotes voluntary work among employees. Using a sample of 405 employees from Pakistani SMEs, this paper assesses the effect on them of organizational citizenship behavior and transformational leadership, in terms of engaging them in voluntary work that ultimately improves performance; this helps SMEs flourish domestically and internationally. The present research also expands the literature by examining the mediating effect of organizational citizenship behavior and provides new directions for researchers to study transformational leadership and organizational citizenship behavior.

Impacts of aging on murine cartilage biomechanics and chondrocyte in situ calcium signaling.

Aging is the most prominent risk factor for osteoarthritis onset, but the etiology of aging-associated cartilage degeneration is not fully understood. Recent studies by Guilak and colleagues have highlighted the crucial roles of cell-matrix interactions in cartilage homeostasis and disease. This study thus quantified aging-associated changes in cartilage biomechanics and chondrocyte intracellular calcium signaling, [Ca2+]i, activities in wild-type mice at 3, 12 and 22 months of age. In aged mice, articular cartilage exhibits reduced staining of sulfated glycosaminoglycans (sGAGs), indicating decreased aggrecan content. On cartilage surface, collagen fibrils undergo significant thickening while retaining their transverse isotropic architecture, and exhibit signs of fibril crimping in the 22-month group. These compositional and structural changes contribute to a significant decrease in cartilage modulus at 22 months of age (0.55 ± 0.25 MPa, mean ± 95 % CI, n = 8) relative to those at 3 and 12 months (1.82 ± 0.48 MPa and 1.45 ± 0.46 MPa, respectively, n ≥ 8). Despite the decreases in sGAG content and tissue modulus, chondrocytes do not exhibit significantly demoted [Ca2+]i activities in situ, in both physiological (isotonic) and osmotically instigated (hypo- and hypertonic) conditions. At 12 months of age, there exists a sub-population of chondrocytes with hyper-active [Ca2+]i responses under hypotonic stimuli, possibly indicating a phenotypic shift of chondrocytes during aging. Together, these results yield new insights into aging-associated biomechanical and mechanobiological changes of murine cartilage, providing a benchmark for elucidating the molecular mechanisms of age-related changes in cell-matrix interactions.

[Clinical efficacy of the combination of miniscrew with clear aligner in controlling the roller coaster effect].

PURPOSE: To investigate the clinical efficacy of miniscrew in controlling the roller coaster effect in long-distance space closure with clear aligner. METHODS: Sixteen adult patients with bimaxillary protrusion were selected. All cases were treated with clear aligner and their four first premolars were extracted. G6 was designed in all cases. In the experimental group, four miniscrews were inserted at the beginning of treatment to control the teeth in three dimensions; while in the control group, the miniscrews were not applied until obvious roller coaster effect appeared. Paired t test was used to analyze the data with Graphpad Prism 6.0 software package. RESULTS: All the extraction space was closed successfully and the lateral profile was improved significantly. The torque of the upper incisor was under well control and no roller coaster effect happened in the experimental group; while in the control group, the lingual inclination of the upper incisors and open bite of the posterior teeth developed(P＜0.05). After the miniscrews intrusion of the upper anterior teeth, the occlusion relationship improved significantly. CONCLUSIONS: Miniscrews effectively prevents and eliminates the roller coaster effect in the process of long-distance space closure with clear aligner.

Hierarchical clock-scale hand-drawn mapping as a simple method for bronchoscopic navigation in peripheral pulmonary nodule.

BACKGROUND: A feasible and economical bronchoscopic navigation method in guiding peripheral pulmonary nodule biopsy is lacking. OBJECTIVE: To investigate the utility of hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation in peripheral pulmonary nodules. METHODS: We developed a hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation in peripheral pulmonary nodules. Patients with peripheral pulmonary nodules were recruited and assigned to two groups in this retrospective study, subjects in VBN group received conventional bronchoscopy in conjunction with virtual bronchoscopic navigation (VBN) and radial probe endobronchial ultrasound (RP-EBUS) for biopsy (VBN group), while HBN group underwent ultrathin bronchoscopy and RP-EBUS under the guidance of hand-drawn bronchoscopic navigation (HBN). The demographic characteristics, procedural time, operating cost and diagnostic yield were compared between these two groups. RESULTS: Forty-eight patients with peripheral pulmonary nodule were enrolled in HBN group, while 42 in VBN group. There were no significant differences between VBN and HBN groups in terms of age, gender, lesion size, location and radiographic type. The time of planning pathway (1.32 vs. 9.79 min, P < 0.001) and total operation (23.63 vs. 28.02 min, P = 0.002), as well as operating cost (758.31 ± 125.21 vs.1327.70 ± 116.25 USD, P < 0.001) were markedly less in HBN group, compared with those in VBN group. The pathological diagnostic efficiency of benign and malignant disease in HBN group appeared similar with those in VBN group, irrespective of the size of pulmonary lesion (larger or smaller than 20 mm). The total diagnostic yield of HBN had no marked difference from that of VBN (75.00% vs. 61.90%, P = 0.25). CONCLUSIONS: Hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation could serve as a feasible and economical method for guiding peripheral pulmonary nodule biopsy, providing a comparable diagnostic yield in comparison with virtual bronchoscopic navigation.

Resveratrol reduces inflammatory response and detrimental effects in chronic cerebral hypoperfusion by down-regulating stimulator of interferon genes/TANK-binding kinase 1/interferon regulatory factor 3 signaling.

Inflammatory responses induced by chronic cerebral hypoperfusion (CCH) play a critical role in the progression of vascular dementia. Stimulator of interferon genes (STING) signaling function as a key mediator of inflammation and immunological responses in the central nervous system (CNS), and resveratrol (RES) exerts potent anti-inflammatory effects. However, the role of STING signaling and the relationship between RES and STING signaling in persistent hypoperfusion-induced cerebral inflammation remain unclear. In this study, Sprague-Dawley rats were subjected to either Sham or bilateral common carotid artery occlusion (2VO) surgery and received RES or vehicle daily by intraperitoneal injection for 4 or 8 weeks. Morris's water maze was used for the analysis of cognitive function. The neuroinflammatory responses in white matter and hippocampus of the rat brain were assessed by Western blot, Immunofluorescence staining, and qRT-PCR analyses. Myelin integrity, neutrophil infiltration, and microglia proliferation were assessed by Immunohistochemistry and histologic analysis. We demonstrated that after CCH, neurons, microglia, and astrocyte under endoplasmic reticulum (ER) stress upregulated the expression of STING, TANK-binding kinase 1 (TBK1), and the transcription factor interferon regulatory factor 3 (IRF3), as well as translocation of IRF3 into the nucleus. These were accompanied by infiltration of neutrophils, activation of microglia, and overproduction of proinflammatory mediators. Improvements in cognitive deficits were related to reduced hippocampal neuronal cell death and increased myelin integrity in RES-treated rats. The neuroprotective effects of RES were associated with suppression of the expression of tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule 1 (ICAM-1), VCAM-1, interferon-ß (IFN-ß), and IL-1ß, likely through mitigation of the STING/TBK1/IRF3 pathway. These inhibitory effects exerted by RES also inhibited the levels of myeloperoxidase, reduced excess expression of reactive astrocytes, and activated microglia. In conclusion, the STING/TBK1/IRF3 axis may be critical for proinflammatory responses in cerebral tissue with persistent hypoperfusion, and RES exerts its anti-inflammatory effects by suppressing STING/TBK1/IRF3 signaling.

The triglyceride glucose index is associated with the cerebral small vessel disease in a memory clinic population.

BACKGROUND AND OBJECTIVES: Insulin resistance (IR) has been associated with the cerebral small vessel disease (cSVD). However, as the surrogate marker of IR, there is little known about the relationship between the triglyceride glucose (TyG) index and cSVD. In this cross-sectional study, we aimed to evaluate the relationship between the TyG index and cSVD in a memory clinic population and explore the value of TyG index to improve the risk stratification of cSVD. METHODS: We included participants who attended our memory clinic from January 2016 to December 2020. TyG index was determined as ln [fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. We assessed lacunes, microbleeds, white matter hyperintensity (WMH) and enlarged perivascular spaces (EPVS) on MRI and calculated the total cSVD burden. RESULTS: A total of 297 subjects were included (median age: 65 years, male sex: 64.98%). In the adjusted model, when dividing TyG index into quartiles, subjects with TyG index in the top quartile, compared with those in the bottom quartile, were more likely to have lacunes (P = 0.035), moderate-severe WMH (P = 0.001), a higher grade of deep WMH (P = 0.004), a higher grade of PVWMH (P = 0.032), a higher grade of EPVS (P = 0.002), and a higher cSVD score (P < 0.001). When introducing TyG index into traditional risk factors to predict moderate to severe cSVD, both area under the curve (0.745 vs 0.802, P = 0.003) and integrated discrimination index (0.080, 95% CI 0.050-0.110, P < 0.001) displayed an improvement from TyG index. CONCLUSIONS: The TyG index is correlated with cSVD and may have the potential to be a surrogate marker of insulin resistance and optimize the risk stratification.