Corrigendum to "Assessing pripherally inserted central catheter tip location in multiple postures: A case report" [Asia-Pacific J Oncol Nurs 10 (2023) 100238].

[This corrects the article DOI: 10.1016/j.apjon.2023.100238.].

A New Theranostic Platform Against Gram-Positive Bacteria Based on Near-Infrared-Emissive Aggregation-Induced Emission Nanoparticles.

Infections induced by Gram-positive bacteria pose a great threat to public health. Antibiotic therapy, as the first chosen strategy against Gram-positive bacteria, is inevitably associated with antibiotic resistance selection. Novel therapeutic strategies for the discrimination and inactivation of Gram-positive bacteria are thus needed. Here, a specific type of aggregation-induced emission luminogen (AIEgen) with near-infrared fluorescence emission as a novel antibiotic-free therapeutic strategy against Gram-positive bacteria is proposed. With the combination of a positively charged group into a highly twisted architecture, self-assembled AIEgens (AIE nanoparticles (NPs)) at a relatively low concentration (5 µm) exhibited specific binding and photothermal effect against living Gram-positive bacteria both in vitro and in vivo. Moreover, toxicity assays demonstrated excellent biocompatibility of AIE NPs at this concentration. All these properties make the AIE NPs as a novel generation of theranostic platform for combating Gram-positive bacteria and highlight their promising potential for in vivo tracing of such bacteria.

Erzhi pills reverse PD-L1-mediated immunosuppression in melanoma microenvironment.

Background: Cancer immunotherapies aimed at activating immune system, especially by blocking immune checkpoints, have become a successful modality for treating patients with advanced cancers. However, its clinical practice is frequently conceded by high outcomes, low initial response rates and severe side effects. New strategies are necessary to complement and advance this biological therapy. Erzhi Pills (EZP) have diverse pharmaceutical effects including immune regulation, anti-tumor and anti-senescence. We hypothesized that EZP could exert its antitumor effect through immunomodulation. Purpose: The aim of this study was to investigate the effects of EZP on anti-tumor activities, and define its molecular mechanisms. Methods: By applying melanoma model with high immune infiltrates, we determined the anti-melanoma effect of EZP. To identify whether this effect was mediated by direct targeting tumor cells, cell viability and apoptosis were examined in vitro. Network pharmacology analysis was used to predict the potential mechanisms of EZP for melanoma via immune response. Flow cytometry, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA) and crystal violet (CV) experiments were performed to detect T cell infiltrations and functions mediated by EZP. The mechanism of EZP was further investigated by western blotting both in vivo and in vitro. Results: The administration of EZP significantly inhibited tumor weight and volume. EZP extract could only slightly reduce cell viability and induce melanoma apoptosis. Network pharmacology analysis predicted that JAK-STAT signaling pathway and T cell receptor signaling pathway might be involved during EZP treatment. Flow cytometry and IHC analyses showed that EZP increased the number of CD4+ T cells and enhanced the function of CD8+ T cells. In co-culture experiments, EZP elevated killing ability of T cells. Western blotting showed that EZP treatment reduced PD-L1 signaling pathway. Conclusion: These findings indicated that EZP exerted anti-melanoma effects by inducing apoptosis and blocking PD-L1 to activate T cells. EZP might represent a promising candidate drug for cancer immunotherapies.

The value of Korean, American, and Chinese ultrasound risk stratification systems combined with BRAF(V600E) mutation for detecting papillary thyroid carcinoma in cytologically indeterminate thyroid nodules.

PURPOSE: To investigate the value of Korean, American, and Chinese ultrasound risk stratification systems combined with BRAF(V600E) mutation in the detection of papillary thyroid carcinoma (PTC)within cytologically indeterminate thyroid nodules (CITNs). METHODS: A single-center retrospective study encompassed 511 CITNs selected from 509 patients between January 2020 and July 2023.Each nodule underwent surgical treatment and was classified according to three distinct systems. Receiver operating characteristic (ROC) curves were plotted using histopathological diagnosis as the reference standard, and diagnostic performance was compared. RESULTS: The three ultrasound stratification systems showed an elevated malignant risk with increasing grades (all P for trend2 < 0.001). The cut-off values for Korean, American, and Chinese systems were 5, 5, and 4c, and their respective area under the curves (AUCs) were 0.735, 0.778, and 0.783.The combination of BRAF (V600E) mutation significantly enhanced the diagnostic efficacy for the Korean(0.773vs0.735, P < 0.001), American (0.809vs0.778, P < 0.001) and Chinese (0.815vs0.783, P < 0.001) stratification systems in distinguishing CITNs without compromising specificity. When the three stratification systems were applied individually or combined with BRAF (V600E) mutation, the AUCs of the American and Chinese systems were similar (all P > 0.05), both of which were higher than the AUC of the Korean system (all P < 0.05). The American system exhibited higher specificity compared to the Chinese and Korean systems (all P < 0.001), whereas the Chinese system demonstrated higher sensitivity and accuracy when compared to the American and Korean systems (all P < 0.001). CONCLUSION: Korean, American and Chinese stratification systems present potential in the differential diagnosis of CITNs. BRAF (V600E) mutation can significantly improve the detection rate of malignant nodules within CTNs, particularly PTC. Notably, the American and Chinese systems demonstrate superior overall diagnostic performance among these systems.

Genetically predicted obstructive sleep apnea is causally associated with an increased risk for periodontitis.

BACKGROUND: Although obstructive sleep apnea (OSA) and periodontitis are associated, whether this association is causative is uncertain. METHODS: We conducted a bidirectional Mendelian randomization (MR) analysis using data from publically accessible genome-wide association studies. The single-nucleotide polymorphisms (SNPs) for OSA were derived from 16,761 cases and 201,194 controls. The pooled data of periodontitis association involved up to 17,353 individuals. Disease-associated single-nucleotide polymorphisms were selected as an instrumental variable at the genome-wide significance level (p < 5.0 × 10- 6). Subsequently, the causal effects were estimated using three different methods: inverse variance weighting (IVW), MR-Egger, and weighted median. Then, these causal estimates were expressed as dominance ratios [odds ratio (OR)]. RESULTS: The MR analysis revealed that genetically determined OSA promotes the development of periodontitis [ IVW OR = 1.117, 95% confidence interval (CI) = 1.001-1.246, p = 0.048). Furthermore, no causal effect of genetically predicted periodontitis on OSA was noted in the reverse MR analysis (IVW OR = 1, 95% CI: 0.95-1.06, p = 0.87). The trend in results from the MR-Egger regression and weighted median (WM) was consistent with that in results from the IVW method. The robustness of the results was confirmed by the sensitivity analysis. CONCLUSIONS: In summary, the results of our MR investigation suggest an association between OSA and periodontitis, proposing that early screening and treatment of OSA is beneficial for the prevention and prognosis of periodontitis.

Assessing pripherally inserted central catheter tip location in multiple postures: A case report.

This report presents a case involving a 21-year-old male patient with acute promyelocytic leukemia, where the peripherally inserted central catheter (PICC) tip location was diagnosed differently using ultrasound and computed tomography. The PICC was inserted into the left upper arm via the basilic vein. Echocardiography performed in the left lateral recumbent position suggested the PICC tip to be in the right atrium, deepest at the level of the tricuspid annulus. However, trans-catheter contrast-enhanced echocardiography, performed with a different posture involving left shoulder abduction and slight external rotation, revealed the tip to be at the cavo-atrial junction. Additionally, chest computed tomography, conducted in the supine position with raised arms, indicated the tip to be located at the upper one-third of the superior vena cava. These contradictory diagnoses can be attributed to the use of different body postures during the assessments. Considering the clinical efficacy and safety, it is crucial to fully consider the influence of multiple postures on PICC tip location during placement and determination. We recommend incorporating at least two opposite extreme daily postures to assess the nearest and farthest positions of the tip, ensuring effective and safe PICC placement and reducing the risk of complications.

Effects of modified triangular flap for third molar extraction on distal periodontal health of second molar: A randomized controlled study.

Objective: The aim of this study was to assess the effect of flap design for impacted mandibular third molar extraction on the distal periodontal tissue of their neighbors clinically, immunologically, and microbiologically. Study design: This randomized controlled study comprised 100 patients who were allocated randomly to receive either a triangular flap or a modified triangular flap. The distal periodontal pocket depth, plaque index, bleeding on probing, the presence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia, and the level of interleukin-1ß, interleukin-8 and matrix metalloproteinase-8 of adjacent second molars were measured at baseline, and 1, 4 and 8 weeks after surgery. Results: After 1 and 4 weeks, distal periodontal conditions of adjacent second molars deteriorated, along with an increase in subgingival microbiota and inflammatory factors in both groups. And compared to the modified triangular flap group, the triangular flap group significantly increased (p < 0.05). Prevotella intermedia, interleukin-1ß and probing depth were positively correlated in both groups. After 8 weeks, they returned to the preoperative level. Conclusions: In this study, both flap designs for impacted mandibular third molar extractions was associated with worse clinical periodontal indices, increased inflammatory biomarkers of gingival crevicular fluid, and more subgingival pathogenic microbiota within 4 weeks. But compared with the triangular flap, the modified triangular flap was better for distal periodontal health of adjacent second molars, which provides certain directions for clinical treatment.

The effect of APN, hs-CRP and APN/hs-CRP in periodontitis with DAA.

BACKGROUND: Common chronic infections induced low-grade inflammation has been correlated with atherosclerosis as supported by strong evidence. The balance between pro-and anti-inflammatory factors was exploited to elucidate the effects of chronic periodontitis on diabetes-associated atherosclerosis. METHODS: Study subjects encompassed 30 SPF male rats randomly divided into four groups: A group (NC), B group (T2DM), C group (CP), D group (DM + CP). After developing the model, blood samples were collected from the angular vein analyze serum APN, hs-CRP, and blood lipid. the carotid artery was isolated for HE staining. RESULT: Compared with group A, the serum APN in group B, C and D decreased gradually with the progression of the disease. Serum hs-CRP in group B, C and D was significantly increased. At T3, T4 and T5 in group B, C and D, APN/hs-CRP significantly decreased. TC, LDL and TG significantly increased in group B, D; HDL significantly decreased in group C. Carotid artery HE staining showed: compared with group A, different degrees of endothelial defect, destruction of elastic fibers in the middle membrane, disorder of smooth muscle arrangement, and partial dissolution 、 fragmentation and Calcium salt deposition necrosis occurred in group B, C and D. CONCLUSION: Enhanced systemic inflammation, decreased adiponectin level, and disorganized lipid metabolism with or without type 2 diabetes attributed to local inflammation of periodontitis can result in an imbalance of pro-inflammatory and anti-inflammatory effects. Therefore, it's more meaningful to predict the progression of DAA with anti-inflammatory/pro-inflammatory variation.

[Diagnostic Value of American Thyroid Association Guidelines,American College of Radiology Thyroid Imaging Reporting and Data System,and Chinese Thyroid Imaging Reporting and Data System Alone and Combined With BRAFV600E Mutation in Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance].

Objective To explore the diagnostic efficacy of American Thyroid Association(ATA)guidelines,American College of Radiology Thyroid Imaging Report and Data System(ACR-TIRADS),and Chinese Thyroid Imaging Reporting and Data System(C-TIRADS)alone and combined with BRAFV600E mutation in atypia of undetermined significance/follicular lesion of undetermined significance(AUS/FLUS).Methods A total of 138 patients who underwent ultrasound-guided fine needle aspiration(FNA)in the Chinese PLA General Hospital from January 2020 to May 2023 were selected.The clinicopathological and ultrasound characteristics were retrospectively analyzed for each nodule.Each nodule underwent preoperative BRAFV600E mutation testing and was diagnosed according to the ATA guidelines,ACR-TIRADS,and C-TIRADS.The diagnostic efficacy of ATA guidelines,ACR-TIRADS,and C-TIRADS alone and combined with BRAFV600E mutation was assessed based on the results of histopathological diagnosis.Results The 138 AUS/FLUS thyroid nodules included 45(32.6%)benign ones and 93(67.4%)malignant ones.The patient age(t=1.444,P=0.151),gender(χ2=0.259,P=0.611),and location of nodules(χ2=2.055,P=0.358)had no statistical significance for the differentiation between benign and malignant nodules,while nodule size(Z=2.500,P=0.012),echo(χ2=14.693,P<0.001),composition(χ2=17.075,P<0.001),aspect ratio ≥1(χ2=9.477,P=0.002),and microcalcification(χ2=6.892,P=0.009)were of significance for the differentiation.When applied alone,BRAFV600E mutation showed high specificity(95.56%)and positive predictive value(95.65%).Among the three ultrasound grading systems,ACR-TIRADS had the highest sensitivity(χ2=37.923,P<0.001;χ2=40.462,P<0.001)and accuracy(χ2=81.595,P<0.001;χ2=76.912,P<0.001),while C-TIRADS had the highest specificity(χ2=11.746,P<0.001;χ2=21.235,P<0.001).However,the three systems showed no statistically significant difference in the diagnostic efficiency when applied alone(Z=1.177,P=0.239;Z=0.213,P=0.831;Z=1.016,P=0.310).The combination of BRAFV600E mutation with ACR-TIRADS or C-TIRADS improved the diagnostic efficacy of BRAFV600E mutation in distinguishing the benign and malignant AUS/FLUS nodules(Z=2.107,P=0.035;Z=2.752,P=0.006).The combination of ATA guidelines with BRAFV600E mutation increased the diagnostic accuracy of BRAFV600E mutation(χ2=20.679,P<0.001),while it had no statistically significant difference in distinguishing the benign and malignant AUS/FLUS nodules(Z=1.321,P=0.186).The combination of ATA guidelines,ACR-TIRADS,or C-TIRADS with BRAFV600E mutation improved the diagnostic efficacy of ultrasound grading systems for AUS/FLUS nodules(Z=2.770,P=0.006;Z=2.770,P=0.006;Z=2.890,P=0.004).Specifically,ACR-TIRADS combined with BRAFV600E mutation showed the highest sensitivity(χ2=4.712,P=0.030;χ2=4.712,P=0.030),while C-TIRADS combined with BRAFV600E mutation showed the highest accuracy(χ2=77.627,P<0.001;χ2=85.827,P<0.001).However,there were no statistically significant differences in diagnostic performance between the combinations(Z=1.276,P=0.202;Z=0.808,P=0.419;Z=1.615,P=0.106).Conclusion ATA guidelines,ACR-TIRADS,and C-TIRADS combined with BRAFV600E mutation can improve the diagnostic efficacy of BRAFV600E mutation or ultrasound grading system alone in AUS/FLUS nodules,which can facilitate the further management and treatment of such patients.

Diagnostic Value of Color Doppler Ultrasound and Contrast-Enhanced Ultrasound in the Artery Steal Syndrome After Orthotopic Liver Transplantation.

Purpose: This study aimed to investigate the application of color Doppler ultrasound (CDU) and contrast-enhanced ultrasound (CEU) in the early diagnosis of arterial steal syndrome (ASS) after orthotopic liver transplantation (OLT). Patients and Methods: A total of 1827 patients received OLT in our department between January 2007 and December 2021, and CDU and CEU were performed after surgery. Ultrasonographic data were collected and further analyzed. ASS was confirmed by digital subtraction angiography (DSA), and the use of splenic artery embolization was dependent on the DSA findings and clinical conditions. The ultrasonographic data were collected before and after embolization. Results: ASS was found in 23 patients (23/1827; 1.26%). CDU: the portal vein velocity was higher than normal in 17 patients (52.83±21.74 cm/s); the hepatic artery flow signals disappeared in 7 patients; the hepatic artery velocity was 13.57±5.85 cm/s in 16 patients. In 23 patients, the spleen artery velocity was 170.12±32.04 cm/s. CEU: the hepatic artery was observed in 7 patients without hepatic artery flow signals on CDU; in 23 patients, the contrast agent reached the portal vein at the presence of contrast in the hepatic artery or earlier (difference: 2.21±1.09 s). Splenic artery embolization was done in 17 of 23 patients with ASS. The hepatic artery flow velocity, hepatic artery resistance index, splenic artery velocity and time to the presence of contrast were significantly improved after embolization (P<0.05). Conclusion: CDU and CEU are the preferred, effective tools in the diagnosis of ASS. Reduced peak hepatic artery velocity, increased spleen artery velocity and reduced time difference in the contrast reaching the portal vein and hepatic artery are indicative of ASS.

Uniform Lithium Deposition Induced by ZnFx(OH)y for High-Performance Sulfurized Polyacrylonitrile-Based Lithium-Sulfur Batteries.

Lithium metal batteries are emerging as the next generation of high-density electrochemical energy storage systems because of the ultra-high specific capacity and ultra-low electrochemical potential of the Li metal anode. However, the uneven Li deposition on commercial Cu current collectors result in low Coulombic efficiencies (CEs) and poor cycle life. In this research, we proposed the modification of ZnFx(OH)y on Cu foils to expand the lifespan. As-generated ZnLi alloy and LiF could promote uniform Li nucleation and deposition, thus resulting in an improved Li plating/stripping CE and extended cycle life. The Li-S battery with sulfurized polyacrylonitrile cathode and Li-ZnFx(OH)y@Cu anode (N/P ratio of 1.5:1) maintains 95% capacity after 60 cycles, proving the feasibility of ZnFx(OH)y@Cu for practical applications.

The underlying molecular mechanisms and biomarkers of plaque vulnerability based on bioinformatics analysis.

AIM: The study aimed to identify the underlying differentially expressed genes (DEGs) and mechanism of unstable atherosclerotic plaque using bioinformatics methods. METHODS: GSE120521, which includes four unstable samples and four stable atherosclerotic samples, was downloaded from the GEO database. DEGs were identified using LIMMA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were performed using the Database for metascape Visualization online tool. Based on the STRING database, protein-protein interactions (PPIs) network among DEGs were constructed. Regulatory networks were visualized using Cytoscape. We use the xCell to analyze the different immune cell subtypes. RESULTS: A total of 1626 DEGs (1034 up-regulated and 592 down-regulated DEGs) were identified between unstable and stable samples. I pulled 62 transcription factors (34 up-regulated TFs and 28 down-regulated TFs) from the Trust database. The up-regulated TFs were mainly enrichment in positive regulation of myeloid leukocyte differentiation, and the down-regulated TFs were mainly enrichment in connective tissue development. In the PPI network, RB1, CEBPA, PPARG, BATF was the most significantly up-regulated gene in ruptured atherosclerotic samples. The immune cell composition enriched in CD cells and macrophages in the unstable carotid plaque. CONCLUSIONS: Upregulated RB1, CEBPA, PPARG, BATF and down-regulated SRF, MYOCD, HEY2, GATA6 might perform critical promotional roles in atherosclerotic plaque rupture, furthermore, number and polarization of macrophages may play an important role in vulnerable plaques.

Functional Polymer Materials for Advanced Lithium Metal Batteries: A Review and Perspective.

Lithium metal batteries (LMBs) are promising next-generation battery technologies with high energy densities. However, lithium dendrite growth during charge/discharge results in severe safety issues and poor cycling performance, which hinders their wide applications. The rational design and application of functional polymer materials in LMBs are of crucial importance to boost their electrochemical performances, especially the cycling stability. In this review, recent advances of advanced polymer materials are examined for boosting the stability and cycle life of LMBs as different components including artificial solid electrolyte interface (SEI) and functional interlayers between the separator and lithium metal anode. Thereafter, the research progress in the design of advanced polymer electrolytes will be analyzed for LMBs. At last, the major challenges and key perspectives will be discussed for the future development of functional polymers in LMBs.

A Diluted Electrolyte for Long-Life Sulfurized Polyacrylonitrile-Based Anode-Free Li-S Batteries.

Lithium-metal batteries have attracted extensive research attention because of their high energy densities. Developing appropriate electrolytes compatible with lithium-metal anodes is of great significance to facilitate their practical application. Currently used electrolytes still face challenges of high production costs and unsatisfactory Coulombic efficiencies of lithium plating/stripping. In this research, we have developed a diluted electrolyte which is compatible with both lithium-metal anode and sulfurized polyacrylonitrile cathode. It presents a very high Li plating/stripping Coulombic efficiency of 99.3% over prolonged cycling, and the as-assembled anode-free Li-S battery maintains 71.5% of the initial specific capacity after 200 cycles at 0.1 A g-1. This work could shed light on designing a low-cost and high-performance liquid electrolyte for next-generation high-energy batteries.

Danshensu prevents thrombosis by inhibiting platelet activation via SIRT1/ROS/mtDNA pathways without increasing bleeding risk.

BACKGROUND: Coronary thrombosis and its correlated disorders are main healthcare problems globally. The therapeutic effects of current treatments involving antiplatelet drugs are not fully satisfactory. Danshensu (DSS) is an important monomer obtained from Salvia miltiorrhiza roots that have been widely employed for vascular diseases in medicinal practices. Nonetheless, the underlying mechanisms of DSS are not fully unraveled. PURPOSE: The objective of this study was to penetrate the antithrombotic and antiplatelet mechanisms of DSS. METHODS: Network pharmacology assay was used to forecast the cellular mechanisms of DSS for treating thrombosis. The work focused the impacts of DSS on platelet activation by analyzing aggregation and adhesion in vitro. Flow cytometry, western blotting, CM-H2DCFDA staining and mitochondrial function assays were performed to reveal the molecular mechanisms. The model of common carotid artery thrombus induced by ferric chloride was established. The wet weight of thrombus was measured, and the thrombosis was observed by hematoxylin and eosin (H&E) staining, in order to support the inhibitory effect of DSS on thrombosis. RESULTS: Data mining found the antithrombotic effect of DSS is related to platelet activation and the core target is silent information regulator 1 (SIRT1). We confirmed that DSS dose-dependently inhibited platelet activation in vitro. DSS was further demonstrated to induce the expression of SIRT1 and decreased reactive oxygen species (ROS) burden and thereby prevented mitochondrial dysfunction. Mitochondrial function tests further indicated that DSS prevented mitochondrial DNA (mtDNA) release, which induced activation of platelet in a dendritic cell specific intercellular-adhesion-molecule-3 grabbing non-integrin (DC-SIGN)-dependent manner. In carotid artery injury model induced by ferric chloride, DSS inhibited the development of carotid arterial thrombosis. More encouragingly, in tail bleeding time assay, DSS did not augment bleeding risk. CONCLUSION: These findings indicated that DSS effectively inhibited platelet activation by depressing the collection of ROS and the release of platelet mtDNA without arousing hemorrhage risk. DSS might represent a promising candidate drug for thrombosis and cardiovascular disease therapeutics.

Evaluation of staff satisfaction after the implementation of a daily goals sheet in the routine work of an oral outpatient department and its influence on work efficiency.

BACKGROUND: In March 2021, the supervision group of our hospital inspected the daily work of the outpatient department in the branch and found many problems in the process, such as an excessive number of daily check-up forms, nurses' confusion regarding the daily check-up process, and the omission of daily check-up items. Therefore, focusing on these problem, our hospital established a quality improvement team to conduct a status survey and perform this study. This study evaluated the feasibility, availability and sustainability of using a daily goals sheet in the routine work of a stomatological outpatient department and investigated the satisfaction of the nursing staff with the sheet. METHODS: After determining the theme of this study through the status survey, 60 nurses were randomly selected and divided into an experimental group and a control group by a random grouping method. Then, the study was divided into two stages: Applying the PDCA cycle method and following the MECE (Mad Exclusive, Collectively Exhaustive) principle to design, manufacture and apply the daily goals sheet. After the expert group performed Stage one, an analysis of work efficiency and routine omissions and a staff satisfaction survey were carried out. The results of the groups either using the daily goals sheet (n = 30) or not (n = 30) were analysed and compared. RESULTS: The average work time of the daily goals sheet group was 15.20 ± 1.70 min, and that of the nondaily goals sheet group was 25.30 ± 2.70 min (P < 0.001). The omission rate was 0% in the daily goals sheet group and 16.67% in the nondaily goals sheet group. Staff satisfaction with the use of the daily goals sheet was high. CONCLUSION: The daily goals sheet can make routine work more efficient and convenient in a stomatological outpatient department. It is recommended for use in stomatological outpatient departments or hospitals.

Periodontitis exacerbates endothelial dysfunctions partly via endothelial-mesenchymal transition in streptozotocin-induced diabetes rats.

OBJECTIVES: Periodontal infections are related to the expansion of diabetes cardiovascular problems. However, the pathological process and probable mechanism remain unexplained. This study investigated the impact of periodontitis on streptozotocin (STZ)-induced diabetes rats' carotid artery. METHODS: We randomized 24 Sprague-Dawley (SD) rats into four groups: control, chronic periodontitis (CP), diabetes mellitus (DM), and DM +CP groups. Fasting blood glucose (FBG) and hemoglobin A1c (HBA1c ) were measured to verify the establishment of the DM model. After euthanasia, the maxillary was collected for further studies like hematoxylin-eosin (HE), Masson staining, and micro-computed tomography (micro-CT) analysis. Immunofluorescence (IF) staining was used to detect endothelial-mesenchymal transition (EndMT)-related markers in carotid artery wall. We further used ELISA and quantitative real-time PCR to investigate the effect of high glucose (HG) and Porphyromonas gingivalis lipopolysaccharide (P.g-LPS) on human umbilical vein endothelial cells (HUVECs). RESULTS: Compared with DM and CP groups, bone resorption and pathological changes of the vascular wall were the most serious in the DM+CP group. The vascular wall of the DM+CP group had a higher level of interleukin (IL)-6 and vascular cell adhesion molecule 1 (VCAM-1). The carotid artery vascular wall of the DM+CP group contained more cells that expressed both mesenchymal and endothelial cell markers, along with elevated transcription factor levels. Furthermore, P.g-LPS and HG upregulated the inflammatory cytokines expression and caused phenotypic changes of HUVECs in vitro. CONCLUSION: Periodontitis exacerbates endothelial dysfunctions partly via endothelial-mesenchymal transition in STZ-induced diabetes rats.

Spatiotemporal dynamics of brain function during the natural course in a dental pulp injury model.

PURPOSE: Toothache, a common disorder afflicting most people, shows distinct features at different clinical stages. This study aimed to depict metabolic changes in brain and investigate the potential mechanism involved in the aberrant affective behaviors during the natural process of toothache. METHODS: We investigated the spatiotemporal patterns of brain function during the natural course of toothache in a rat model of dental pulp injury (DPI) by using positron emission tomography (PET). RESULTS: Glucose metabolism peaked on the 3rd day and gradually decreased in several brain regions after DPI, which was in line with the behavioral and histological results. PET imaging showed that visual pathway was involved in the regulation of toothache. Meanwhile, the process of emotional regulation underlying toothache was mediated by N-methyl-D-aspartic receptor subunit 2B (NR2B) in the caudal anterior cingulate cortex (cACC). CONCLUSION: Our results revealed the spatiotemporal neurofunctional patterns during toothache process and preliminarily elucidated the role of NR2B in cACC in the regulation of toothache-related affective behaviors.

Odontoblast apoptosis and intratubular mineralization of sclerotic dentin with aging.

OBJECTIVES: The aims of the study were to evaluate the roles of odontoblast apoptosis in the progression of tubular sclerosis of teeth from donors at different ages and assess its correlation to chemical composition and mechanical properties. DESIGN: Healthy human teeth were obtained and divided into young (age ≤ 25, n = 12) and old (age ≥ 60, n = 12) groups. Odontoblasts were counted with standard hematoxylin and eosin staining. Odontoblast apoptosis within dentinal tubules was determined by cleaved caspase-3 immunostaining. Teeth in each group were evaluated by dynamic nanoindentation and energy-dispersive X-ray spectroscopy (EDS). RESULTS: The number of odontoblasts decreased significantly with age. The most prominent change occurred in the apical third of roots. Odontoblastic apoptosis was visualized within dentinal tubules. The apoptosis staining fraction was significantly higher in the outer and inner dentin of old teeth when compared with young teeth (p < 0.05). EDS showed increased calcium content in peritubular dentin but a decrease in the intertubular dentin with increasing age. Scanning based nanoindentation showed that the old intertubular dentin exhibited a significantly higher elastic modulus. CONCLUSIONS: Odontoblast apoptosis, starting at the cell extension in dentinal tubules and proceeding from outer to inner dentin, contributes to the stoichiometric Ca/P ratio in peritubular dentin, which is potentially responsible for intratubular mineralization due to an imbalance of calcium and phosphorous ions.

Promotion or inhibition of extracellular vesicle release: Emerging therapeutic opportunities.

Extracellular vesicles (EVs) are vehicles of intercellular communication that are released from various cell types under physiological and pathological conditions, with differing effects on the body. Under physiological conditions, EVs mediate cell-to-cell and intertissue communication and participate in maintaining homeostasis. Certain EV types have emerged as biological therapeutic agents in various fields, such as cell-free regenerative medicine, drug delivery and immunotherapy. However, the low yield of EVs is a bottleneck in the large-scale implementation of these therapies. Conversely, more EVs in the microenvironment in other circumstances, such as tumor metastasis, viral particle transmission, and the propagation of neurodegenerative disease, can exacerbate the situation, and the inhibition of EV secretion may delay the progression of these diseases. Therefore, the promotion and inhibition of EV release is a new and promising field because of its great research potential and wide application prospects. We first review the methods and therapeutic opportunities for the regulation of EV release based on the mechanism of EV biogenesis and consider the side effects and challenges.