Multidisciplinary clinical decision-making of anterior diastema closure.

Anterior diastema is a common esthetic defect in China. The general treatment for a patient with diastemata, including orthodontics and direct and indirect restorations, is a multidisciplinary clinical procedure covering the orthodontics, operative dentistry, general dentistry, and prosthodontics department. Given the diversity of departments and the complex etiology of this defect, decision-making regarding the closing methods and time selection is undefined and unintegrated, which makes the long-term stability of closure unpredictable. This article proposed an etiology-based decision tree with actual measurement of diastemata width for diastemata closure. The decisional steps include classifying the etiological factors based on patients' medical history and clinical manifestation to evaluate the stability of diastemata. After maintaining the stability of diastemata, contemporary and multidisciplinary treatment plans were selected in accordance with the measured width of diastemata and patients' cosmetic psychology, economics, and available time. These decision trees focus on the challenges of collaboration among dental departments, propose an objective and efficient ways for connections, and promote efficient and effective diastemata closure.

Gingipain and oncostatin M synergistically disrupt kidney tight junctions in periodontitis-associated acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is characterized by rapid renal decline. Periodontitis, a chronic oral inflammatory disease, is increasingly associated with renal dysfunction. Although periodontitis is recognized as a contributor to kidney damage, the mechanisms linking it to AKI remain unclear. METHODS: This study explored the effects of Porphyromonas gingivalis (P. gingivalis) W83-infected periodontitis on AKI in C57BL/6J mice, using ischemia-reperfusion injury 55 days post-infection. Gingipain inhibitors, KYT-1 and KYT-36, were applied. Detection of P. gingivalis was performed using quantitative real-time polymerase chain reaction (qRT-PCR) and PCR, while transcriptome sequencing, qRT-PCR, immunohistochemistry, and immunofluorescence staining assessed renal damage. In vitro, HK-2 cells were exposed to P. gingivalis at a multiplicity of infection of 10 for 48 h, with inhibition by gingipain or oncostatin M (OSM). Disruption of tight junctions (TJs) was quantified using qRT-PCR, transepithelial electrical resistance, and cell counting kit-8 assays. RESULTS: Periodontitis worsened AKI, linked to P. gingivalis infection and renal TJ disruption in the kidney. P. gingivalis infection activated OSM expression, which correlated positively with gingipain. Significantly, OSM and gingipain might collaboratively contribute to the damage of renal TJs, with the reduced expression of TJ proteins. Suppressing gingipain activity presented itself as a protective strategy against the destruction of TJs and the attendant worsening of AKI due to periodontitis. CONCLUSIONS: Our study enhances the understanding of the interplay between periodontitis and AKI, highlighting the harmful impact of P. gingivalis in AKI.

An interdisciplinary treatment to reshape upper anterior displaced teeth by using dynamic occlusal recording with an intraoral scanner.

OBJECTIVE: This article describes an interdisciplinary treatment that helped a patient with displaced upper anterior teeth. A gingivectomy, root canal therapies, digital smile design, digital wax-up, and guided tooth preparations were applied. CLINICAL CONSIDERATIONS: A patient with pathologically migrated teeth asked for treatment without orthodontic involvement due to a primary failed orthodontic treatment history. A smile photo was taken and superimposed with the dentition in a CAD software to accomplish a digital smile design. The jaw movements were recorded with two different methods, a mechanical articulator and an intraoral scanner with Patient-Specific-Motion function. The occlusal contacts during protrusive and lateral movements were compared and the digital wax-up was designed according to the later occlusal data. An aesthetic crown lengthening and pre-op root canal treatment were carried out in advance accordingly. After guided tooth preparation with a silicone index, the final fixed restorations were manufactured and cemented. A 2-year follow-up showed that our prosthesis functions well. CONCLUSIONS: This clinical report revealed that an intraoral scanner with Patient-Specific-Motion function can effectively record individual dynamic occlusal patterns and these data can be integrated into the CAD/CAM process to enhance the fulfillment of clinical requirements. CLINICAL SIGNIFICANCE: This clinical procedure with a 2-year follow-up demonstrated that a prosthodontic-based interdisciplinary treatment of pathologically migrated teeth using dynamic occlusal recording with an intraoral scanner could achieve satisfactory esthetics in a relatively short treatment period. The Patient Specific Motion module may be used to record a personalized functional movement and the data can be integrated into the design process of the final restorations.

Lactate and Lactylation in Sepsis: A Comprehensive Review.

Sepsis is a disorder of the immune response to infection or infectious factors with high morbidity and mortality in clinical settings. The lactylation of lysine residues, fueled by lactate, plays a pivotal role in its pathophysiology. In conducting a literature review on sepsis-related research, we employed a systematic approach to ensure comprehensiveness and accuracy. Initially, we conducted an extensive literature search through the PubMed database, utilizing a range of keywords including "sepsis", "lactate", "lactylation", and "epigenetic modification". The aim was to capture the most recent research related to the pathophysiological mechanisms of sepsis, metabolic disorders, and the role of lactylation. The results of the literature review revealed a close link between sepsis and metabolic dysfunction, particularly the pivotal role of lactylation in regulating immune responses and inflammatory processes. Lactate, not only an energy metabolic byproduct produced during glycolysis, affects the activity of various proteins, including those involved in immune regulation and cell signaling, through lactylation. In the context of sepsis, changes in the levels of lactylation may be closely associated with the severity and prognosis of the disease. In summary, lactylation, as an emerging type of epigenetic modification, provides a new perspective for the diagnosis and treatment of sepsis. Future research needs to further elucidate the exact mechanisms of lactylation in sepsis and explore its potential as a therapeutic target.

The annual incidence and mortality rates associated with sepsis are on the rise, and to date, no medications or therapies have been proven effective in clinical practice. Glycolysis plays a pivotal role in regulating lactylation, a process derived from lactate generated by cellular glucose metabolism. In the context of sepsis, elevated lactate levels are indicative of a poor prognosis. It is imperative to delve into the mechanisms underlying lactylation alterations during sepsis to enhance our comprehension of its complex pathophysiology and to pinpoint innovative therapeutic targets for the condition.

Staphylococcus aureus wraps around Candida albicans and synergistically escapes from Neutrophil extracellular traps.

Background: NETs, a unique neutrophil immune mechanism, are vital in defending against microbial invasions. Understanding the mechanisms of co-infection by Candida albicans and Staphylococcus aureus, which often leads to higher mortality and poorer prognosis, is crucial for studying infection progression. Methods: In our study, we established a mouse model of subcutaneous infection to characterize the inflammation induced by co-infection. By purifying and extracting NETs to interact with microorganisms, we delve into the differences in their interactions with various microbial species. Additionally, we investigated the differences in NETs production by neutrophils in response to single or mixed microorganisms through the interaction between neutrophils and these microorganisms. Furthermore, we analyzed the gene expression differences during co-infection using transcriptomics. Results: In vivo, C. albicans infections tend to aggregate, while S. aureus infections are more diffuse. In cases of co-infection, S. aureus adheres to and wraps C. albicans. NETs exhibit strong killing capability against C. albicans but weaker efficacy against S. aureus. When NETs interact with mixed microorganisms, they preferentially target and kill the outer layer of S. aureus. In the early stages, neutrophils primarily rely on phagocytosis to kill S. aureus, but as the bacteria accumulate, they stimulate neutrophils to produce NETs. Interestingly, in the presence of neutrophils, S. aureus promotes the proliferation and hyphal growth of C. albicans. Conclusion: Our research has showed substantial differences in the progression of co-infections compared to single-microbial infections, thereby providing scientific evidence for NETs as potential therapeutic targets in the treatment of co-infections.

Ginkgolide C attenuated Western diet-induced non-alcoholic fatty liver disease via increasing AMPK activation.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a metabolic dysregulation-related disorder that is generally characterized by lipid metabolism dysfunction and an excessive inflammatory response. Currently, there are no authorized pharmacological interventions specifically designed to manage NASH. It has been reported that Ginkgolide C exhibits anti-inflammatory effects and modulates lipid metabolism. However, the impact and function of Ginkgolide C in diet-induced NASH are unclear. METHODS: In this study, mice were induced by a Western Diet (WD) with different doses of Ginkgolide C with or without Compound C (adenosine 5 '-monophosphate (AMP)-activated protein kinase (AMPK) inhibitor). The effects of Ginkgolide C were evaluated by assessing liver damage, steatosis, fibrosis, and AMPK expression. RESULTS: The results showed that Ginkgolide C significantly alleviated liver damage, steatosis, and fibrosis in the WD-induced mice. In addition, Ginkgolide C markedly improved insulin resistance and attenuated hepatic inflammation. Importantly, Ginkgolide C exerted protective effects by activating the AMPK signaling pathway, which was reversed by AMPK inhibition. CONCLUSION: Ginkgolide C alleviated NASH induced by WD in mice, potentially via activating the AMPK signaling pathway.

Effect of margin designs and loading conditions on the stress distribution of endocrowns: a finite element analysis.

BACKGROUND: Margin designs and loading conditions can impact the mechanical characteristics and survival of endocrowns. Analyzing the stress distribution of endocrowns with various margin designs and loading conditions can provide evidence for their clinical application. METHODS: Three finite element analysis models were established based on the margin designs: endocrown with a butt-joint type margin (E0), endocrown with a 90° shoulder (E90), and endocrown with a 135° shoulder (E135). The E0 group involved lowering the occlusal surface and preparing the pulp chamber. The E90 group created a 90° shoulder on the margin of model E0, measuring 1.5 mm high and 1 mm wide. The E135 group featured a 135° shoulder. The solids of the models were in fixed contact with each other, and the materials of tooth tissue and restoration were uniform, continuous, isotropic linear elasticity. Nine static loads were applied, with a total load of 225 N, and the maximum von Mises stresses and stress distribution were calculated for teeth and endocrowns with different margin designs. RESULTS: Compared the stresses of different models under the same loading condition. In endocrowns, when the loading points were concentrated on the buccal side, the maximum von Mises stresses were E0 = E90 = E135, and when there was a lingual loading, they were E0 < E90 = E135. In enamel, the maximum von Mises stresses under all loading conditions were E0 > E90 > E135. In dentin, the maximum von Mises stresses of the three models were basically similar except for load2, load5 and load9. Compare the stresses of the same model under different loading conditions. In endocrowns, stresses were higher when lingual loading was present. In enamel and dentin, stresses were higher when loaded obliquely or unevenly. The stresses in the endocrowns were concentrated in the loading area. In enamel, stress concentration occurred at the cementoenamel junction. In particular, E90 and E135 also experienced stress concentration at the shoulder. In dentin, the stresses were mainly concentrated in the upper section of the tooth root. CONCLUSION: Stress distribution is similar among the three margin designs of endocrowns, but the shoulder-type designs, especially the 135° shoulder, exhibit reduced stress concentration.

Cognitive decline in Sprague-Dawley rats induced by neuroplasticity changes after occlusal support loss.

BACKGROUND: Tooth loss is closely related to cognitive impairment, especially affecting cognitive functions involving hippocampus. The most well-known function of the hippocampus is learning and memory, and the mechanism behind is neuroplasticity, which strongly depends on the level of brain-derived neurotrophic factor (BDNF). While research has delved into the possible mechanisms behind the loss of teeth leading to cognitive dysfunction, there are few studies on the plasticity of sensory neural pathway after tooth loss, and the changes in related indicators of synaptic plasticity still need to be further explored. METHODS: In this study, the bilateral maxillary molars were extracted in Sprague-Dawley rats of two age ranges (young and middle age) to establish occlusal support loss model; then, the spatial cognition was tested by Morris Water Maze (MWM). Quantitative real-time PCR (qPCR) and Western Blotting (WB) were used to detect BDNF, AKT, and functional proteins (viz., PSD95 and NMDAR) of hippocampal synapses. Golgi staining was used to observe changes in ascending nerve pathway. IF was used to confirm the location of BDNF and AKT expressed in hippocampus. RESULTS: MWM showed that the spatial cognitive level of rats dropped after occlusal support loss. qPCR, WB, and IF suggested that the BDNF/AKT pathway was down-regulated in the hippocampus. Golgi staining showed the neurons of ascending sensory pathway decreased in numbers. CONCLUSION: Occlusal support loss caused plastic changes in ascending nerve pathway and induced cognitive impairment in rats by down-regulating BDNF and synaptic plasticity.

Prx1/PHB2 axis mediates mitophagy in oral leukoplakia cellular senescence.

BACKGROUND: Oral leukoplakia (OLK) is the most common oral potentially malignant disorder (OPMD), which can be malignantly transformed into oral squamous cell carcinoma (OSCC). Peroxiredoxin1(Prx1) has been predicted to bind to Prohibitin2 (PHB2), which confers to affect OLK progression; however, the mechanism of Prx1/PHB2 mediated mitophagy involved in OLK remains unclear. METHODS: This study aimed to explore the mechanism of the Prx1/PHB2 axis on senescence in OLK through mediating mitophagy. The positive rate of Ki67 and the expression of p21, p16, PHB2, and LC3 in human normal, OLK, and OSCC tissues were detected by immunohistochemical staining. The mitophagy and mitochondrial function changes were then analyzed in Prx1 knockdown and Prx1C52S mutations in dysplastic oral keratinocyte (DOK) cells treated with H2O2. In situ Proximity Ligation Assay combined with co-immunoprecipitation was used to detect the interaction between Prx1 and PHB2. RESULTS: Clinically, the positive rate of Ki67 progressively increased from normal to OLK, OLK with dysplasia, and OSCC. Higher p21, p16, PHB2, and LC3 expression levels were observed in OLK with dysplasia than in normal and OSCC tissues. In vitro, PHB2 and LC3II expression gradually increased with the degree of DOK cell senescence. Prx1/PHB2 regulated mitophagy and affected senescence in H2O2-induced DOK cells. Furthermore, Prx1C52S mutation specifically reduced interaction between Prx1 and PHB2. Prx1Cys52 is associated with mitochondrial reactive oxygen species (ROS) accumulated and cell cycle arrest. CONCLUSION: Prx1Cys52 functions as a redox sensor that binds to PHB2 and regulates mitophagy in the senescence of OLK, suggesting its potential as a clinical target.

Ox-LDL-induced CD80+ macrophages expand pro-atherosclerotic NKT cells via CD1d in atherosclerotic mice and hyperlipidemic patients.

Atherosclerosis is an inflammatory disease of blood vessels involving the immune system. Natural killer T (NKT) cells, as crucial components of the innate and acquired immune systems, play critical roles in the development of atherosclerosis. However, the mechanism and clinical relevance of NKT cells in early atherosclerosis are largely unclear. The study investigated the mechanism influencing NKT cell function in apoE deficiency-induced early atherosclerosis. Our findings demonstrated that there were higher populations of NKT cells and interferon-gamma (IFN-γ)-producing NKT cells in the peripheral blood of patients with hyperlipidemia and in the aorta, blood, spleen, and bone marrow of early atherosclerotic mice compared with the control groups. Moreover, we discovered that the infiltration of CD80+ macrophages and CD1d expression on CD80+ macrophages in atherosclerotic mice climbed remarkably. CD1d expression increased in CD80+ macrophages stimulated by oxidized low-density lipoprotein (ox-LDL) ex vivo and in vitro. Ex vivo coculture of macrophages with NKT cells revealed that ox-LDL-induced CD80+ macrophages presented lipid antigen α-Galcer (alpha-galactosylceramide) to NKT cells via CD1d, enabling NKT cells to express more IFN-γ. Furthermore, a greater proportion of CD1d+ monocytes and CD1d+CD80+ monocytes were found in peripheral blood of hyperlipidemic patients compared with that of healthy donors. Positive correlations were found between CD1d+CD80+ monocytes and NKT cells or IFN-γ+ NKT cells in hyperlipidemic patients. Our findings illustrated that CD80+ macrophages stimulated NKT cells to secrete IFN-γ via CD1d-presenting α-Galcer, which may accelerate the progression of early atherosclerosis. Inhibiting lipid antigen presentation by CD80+ macrophages to NKT cells may be a promising immune target for the treatment of early atherosclerosis.NEW & NOTEWORTHY This work proposed the ox-LDL-CD80+ monocyte/macrophage-CD1d-NKT cell-IFN-γ axis in the progression of atherosclerosis. The proinflammatory IFN-γ+ NKT cells are closely related to CD1d+CD80+ monocytes in hyperlipidemic patients. Inhibiting CD80+ macrophages to present lipid antigens to NKT cells through CD1d blocking may be a new therapeutic target for atherosclerosis.

Daidzein protects endothelial cells against high glucose-induced injury through the dual-activation of PPARα and PPARγ.

Endothelial damage caused by persistent glucose and lipid metabolism disorders is the main reason of diabetic vascular diseases. Daidzein exerts positive effects on vascular dysfunction. Peroxisome proliferator-activated receptors (PPARs) regulate critically glucose and lipid metabolism. However, the interaction of daidzein to PPARs is still insufficiently explored. In this study, the cell proliferation was detected by EdU. The intrinsic activity and binding affinity of daidzein for human PPARs (hPPARs) were estimated by transactivation reporter gene test and HPLC-UV method, respectively. Daidzein significantly reversed high glucose (HG, at 30 mmol/l)-induced injury in HUVECs, which was inhibited by both PPARα and PPARγ antagonist, but no PPARß antagonist. Daidzein selectively activated hPPARα and hPPARγ1, but weakly hPPARß. Additionally, daidzein also bound to both hPPARα and hPPARγ1. The findings suggested that daidzein may be a PPARα and PPARγ dual-agonist. The amelioration of daidzein on HUVECs from hyperglycemia may be mediated by the activation of PPARα and PPARγ receptors.

Identification and verification on prognostic index of glioblastoma immune-related lncRNAs.

BACKGROUND: Glioblastoma (GBM) is the most common cause of primary brain malignancy. Recently, many immune-related long noncoding ribonucleic acids (ir-lncRNAs) are indicated to be closely related to the regulation of the immune microenvironment and immune cell infiltration of GBM. OBJECTIVES: Through the joint analysis of multiple public databases, key ir-lncRNAs in GBM were screened. The ir-lncRNAs were used to construct risk-scoring models and promote the development of novel GBM biomarkers. MATERIAL AND METHODS: In this study, we performed a three-way Venn analysis combined with a least absolute shrinkage and selection operator (LASSO) regression analysis on all lncRNAs in The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) and Imm-Lnc datasets, and identified 10 ir-lncRNAs. Multivariate Cox analysis was used to calculate the coefficient and construct a risk-scoring model. RESULTS: By plotting calibration curves and receiver operating characteristic (ROC) curves, the model showed excellent prediction results. Based on the Tumor Immune Estimation Resource (TIMER) database, the correlation analysis showed that 10 ir-lncRNAs risk scores were related to immune cell infiltration. The enrichment analysis was subsequently performed, which showed that these ir-lncRNAs played an important role in the progression of GBM. Among the 10 lncRNAs, we found that AL354993.1 was highly expressed in GBM, had not been reported, and was shown to be closely related to GBM progression. CONCLUSIONS: In conclusion, the 10 ir-lncRNAs have the potential to predict the prognosis of GBM patients and may play a vital role in the progression of the disease.

Effect of RNA-binding proteins on osteogenic differentiation of bone marrow mesenchymal stem cells.

Tissue regeneration mediated by mesenchymal stem cells (MSCs) is an ideal way to repair bone defects. RNA-binding proteins (RBPs) can affect cell function through post-transcriptional regulation. Exploring the role of RBPs in the process of osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is helpful to find a key method to promote the osteogenic efficiency of BMSCs. By reviewing the literature, we obtained a differentially expressed mRNA dataset during the osteogenic differentiation of BMSCs and a human RBP dataset. A total of 82 differentially expressed RBPs in the osteogenic differentiation of BMSCs were screened by intersection of the two datasets. Functional analysis showed that the differentially expressed RBPs were mainly involved in RNA transcription, translation and degradation through the formation of spliceosomes and ribonucleoprotein complexes. The top 15 RBPs determined by degree score were FBL, NOP58, DDX10, RPL9, SNRPD3, NCL, IFIH1, RPL18A, NAT10, EXOSC5, ALYREF, PA2G4, EIF5B, SNRPD1 and EIF6. The results of this study demonstrate that the expression of many RBPs changed during osteogenic differentiation of BMSCs.

Oridonin suppresses the growth of glioblastoma cells via inhibiting Hippo/YAP axis.

Glioma is a brain tumor that originates from brain or spine glial cells. Despite alternative treatments, the overall survival rate remains low. Oridonin (ORI) is purified from the Chinese herb Rabdosia rubescens, which has exhibited positive effects on tumors. This study aimed to investigate the effect of ORI on U87MG glioblastoma cells and whether the Hippo/YAP-related signaling pathway was involved. Malignant glioblastoma U87MG cells and male athymic nude mice (BALB/cnu/nu) were used as the experimental models. The YAP inhibitor Verteporfin (VP) and the overexpression of YAP were used to investigate its potential relation with glioma. Here, we found that ORI inhibited cell proliferation and promoted cell apoptosis in a dose-dependent manner in U87MG cells. Moreover, ORI inhibited Bcl-2, YAP, and c-Myc protein expression but increased Bax, caspase-3, and p-YAP protein expression. Furthermore, the effect of ORI was also confirmed in a mouse model bearing glioma. ORI reversed the effect of overexpression of YAP. Collectively, oridonin suppressed glioblastoma oncogenesis via the Hippo/YAP signaling pathway and could be a potential therapeutic target in the treatment of glioblastoma.

Photothermal-promoted multi-functional gallic acid grafted chitosan hydrogel containing tannic acid miniaturized particles for peri-implantitis.

Peri-implantitis, a leading cause of implant failure, currently lacks effective therapeutic strategies. Given that bacterial infection and reactive oxygen species overabundance serve as primary pathogenic and triggering factors, respectively, an adhesive hydrogel has been created for in-situ injection. The hydrogel is a gallic acid-grafted chitosan (CS-GA) hydrogel containing tannic acid miniaturized particles (TAMP). This provides antibacterial and antioxidant properties. Therefore, this study aims to evaluate the potential role of this hydrogel in preventing and treating peri-implantitis via several experiments. It undergoes rapid formation within a span of over 20 s via an oxidative crosslinking reaction catalyzed by horseradish peroxidase and hydrogen peroxide, demonstrating robust adhesion, superior cell compatibility, and a sealing effect. Furthermore, the incorporation of TAMP offer photothermal properties to the hydrogel, enabling it to enhance the viability, migration, and antioxidant activity of co-cultured human gingival fibroblasts when subjected 0.5 W/cm2 808 nm near-infrared (NIR) irradiation. At higher irradiation power, the hydrogel exhibits progressive improvements in its antibacterial efficacy against Porphyromonas gingivalis and Fusobacterium nucleatum. It attains rates of 83.11 ± 5.42 % and 83.48 ± 6.855 %, respectively, under 1 W/cm2 NIR irradiation. In summary, the NIR-controlled CS-GA/TAMP hydrogel, exhibiting antibacterial and antioxidant properties, represents a promising approach for the prophylaxis and management of peri-implantitis.

Characteristics of oral microbiota and oral health in the patients treated with clear aligners: a prospective study.

OBJECTIVES: In this prospective clinical study, the effect of clear aligners on periodontal health and oral hygiene was examined. As the same time, microbial changes of the aligner tray and subgingival microbiota community were investigated. METHODS: The study recruited fifteen patients, and clinical parameters were recorded at three different time points: before the initiation of aligner treatment (T0), 1 month after treatment onset (T1), and 3 months after treatment onset (T3). Plaque samples were collected from the inner surface of aligners and subgingival sulcus at each of these time points. The microbial composition of the samples was analyzed using 16S rRNA gene sequencing, and changes were evaluated based on the abundance of amplicon sequence variants (ASVs). RESULTS: Reduction in plaque index and improvement in periodontal health were observed. In aligner tray plaque samples, the relative abundance of Streptococcus increased significantly, as well as the richness and diversity of microbiota decreased substantially as the duration of treatment time. In subgingival plaque samples, alpha and beta diversity of microbiota did not change significantly. CONCLUSIONS: During the clear aligner treatment, the patients' periodontium remained in a healthy condition, and clear aligner treatment had no significant impact on the composition of subgingival microbiota. The structure of the aligner tray microbiota altered significantly at both phylum and genus levels and attracted a unique and less diverse microbiota community. CLABSINABSICAL RELEVANCE: Clear aligner treatment has no significant impact on periodontal health and subgingival microbiota composition of patients.

Prognostic model and treatment choices for patients with primary intracranial central nervous system lymphoma: A population-based study.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a non-Hodgkin lymphoma that occurs in the CNS. With the advancement of medical care, its prognosis and treatment have also undergone tremendous changes. This study aimed to construct a prognostic model and compare the effects of different treatments for intracranial PCNSL. METHODS: Cases diagnosed as PCNSL between 2004 and 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Data were analyzed using Kaplan-Meier method and Cox regression analysis. Nomogram was built and validated using the R program. RESULTS: A total of 2861 PCNSL patients were included in the analysis. Age, year of diagnosis, surgery and chemotherapy were independent predictors for both overall survival (OS) and cancer-specific survival (CSS). A nomogram was established to predict 3-, 5- and 10-year OS and CSS for patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) showed the nomogram had good predictive performance and clinical application value. We also revealed that gross total resection had significantly better OS and CSS than biopsy alone (P < 0.001). Patients who received only chemotherapy had the best prognosis and did not benefit from additional radiotherapy. CONCLUSION: We developed a nomogram to predict patient survival rates based on independent predictors. It is an effective tool to help clinicians make survival predictions. Our results showed that patients can benefit from gross total resection of tumor, if it is feasible, and chemotherapy. The role of radiotherapy remained to be further assessed.

Pyruvate Dehydrogenase Kinase 1 inhibition mediated oxidative phosphorylation enhancement in cartilage promotes osteoarthritis progression.

Osteoarthritis (OA) is a common disease characterized by cartilage degradation. Growing evidence showed that glucose metabolism impacts joint homeostasis and an imbalance between glycolysis and oxidative phosphorylation (OXPHOS) may exacerbate OA progression, however, a definitive link is yet to be established. Here, we report that pyruvate metabolism and oxidative phosphorylation pathway is enriched in OA cartilage through gene set enrichment analysis (GSEA) and expression of Pyruvate Dehydrogenase Kinase 1 (PDK1), an enzyme that can phosphorylate Pyruvate Dehydrogenase (PDH), and inhibit pyruvate fluxes into the tricarboxylic acid (TCA) cycle and to OXPHOS, in articular cartilage is notably reduced through destabilization of medial meniscus (DMM). Moreover, by inhibiting PDK1, cartilage loss is markedly accelerated in DMM-induced OA through extracellular matrix (ECM) degradation and apoptosis of chondrocytes. These results indicate that PDK1 is involved in the progression of OA through accelerating cartilage matrix degradation and synovium inflammation to ameliorate cartilage degeneration.

Evaluation of Er:YAG laser energy transmitted through novel dental zirconia ceramics.

Erbium:yttrium-aluminum-garnet (Er:YAG) laser debonding is a promising removal method in prosthodontics. This study aimed to assess Er:YAG laser energy transmission through novel zirconia ceramics. Five types of ceramic samples: lithium disilicate ceramic (LDC), self-glazed zirconia (SGZ), 3 mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP), 4Y-TZP and 5Y-TZP with 5 thicknesses (0.5, 1.0, 1.5, 2.0, 2.5 mm) and 2 shades (A1, A3), 50 specimens total, were made. Fourier transformation infrared absorption spectra were obtained for each ceramic type, and Er:YAG laser energy transmission tests were conducted for each specimen. The novel zirconia ceramic (SGZ, 4Y-TZP, 5Y-TZP) transmission ranged from 40%-60%. The transmitted laser energy decreased with increasing ceramic thickness, and the differences between different shades were significant (p<0.05). The novel zirconias had a higher translucency than 3Y-TZP at any given thickness and shade, and when the thickness was >1.5 mm, the novel zirconias had a higher translucency than LDC.

Tooth loss impairs cognitive function in SAMP8 mice via the NLRP3/Caspase-1 pathway.

OBJECTIVE: Loss of occlusal support due to tooth loss has been indicated as one of the risk factors for Alzheimer's disease. This study aimed to investigate the relationship between tooth loss and cognitive dysfunction and illustrate the role of neuroinflammation in advancing Alzheimer's disease. MATERIALS AND METHODS: Male 5-month-old senescence-accelerated mouse strain P8 (SAMP8) mice were divided into three groups (n = 7): the C (control), S (sham-operated), and TL (tooth loss) groups. The Morris water maze (MWM) test was performed to assess spatial memory. Additionally, histopathological and molecular assessments of hippocampal tissues were performed. RESULTS: The TL groups exhibited impaired spatial memory in the water maze. Tooth loss induced higher protein expression levels of the neuroinflammation cytokine interleukin-1ß (IL-1ß) in the hippocampus than in the S and C groups. Tooth loss activated the NLRP3 inflammasome and increased the expression of Caspase-1 in the hippocampus. CONCLUSIONS: The findings indicated that tooth loss impairs cognitive function in SAMP8 mice and is closely related to the activation of NLRP3/Caspase-1 in the hippocampus.