The antitumor effects of herbal medicine Triphala on oral cancer by inactivating PI3K/Akt signaling pathway: based on the network pharmacology, molecular docking, in vitro and in vivo experimental validation.

BACKGROUND: This research aimed to investigate the anti-tumor effects and underlying genetic mechanisms of herbal medicine Triphala (TRP) in oral squamous cell carcinoma (OSCC). METHODS: The target genes of Triphala (TRP) in oral squamous cell carcinoma (OSCC) were identified, and subsequent functional enrichment analysis was conducted to determine the enriched signaling pathways. Based on these genes, a protein-protein interaction network was constructed to identify the top 10 genes with the highest degree. Genes deregulated in OSCC tumor samples were identified to be hub genes among the top 10 genes. In vitro experiments were performed to investigate the influence of TRP extracts on the cell metabolic activity, migration, invasion, apoptosis, and proliferation of two OSCC cell lines (CAL-27 and SCC-9). The functional rescue assay was conducted to investigate the effect of applying the inhibitor and activator of an enriched pathway on the phenotypes of cancer cells. In addition, the zebrafish xenograft tumor model was established to investigate the influence of TRP extracts on tumor growth and metastasis in vivo. RESULTS: The target genes of TRP in OSCC were prominently enriched in the PI3K-Akt signaling pathway, with the identification of five hub genes (JUN, EGFR, ESR1, RELA, and AKT1). TRP extracts significantly inhibited cell metabolic activity, migration, invasion, and proliferation and promoted cell apoptosis in OSCC cells. Notably, the application of TRP extracts exhibited the capacity to downregulate mRNA and phosphorylated protein levels of AKT1 and ESR1, while concomitantly inducing upregulation of mRNA and phosphorylated protein levels in the remaining three hub genes (EGFR, JUN, and RELA). The functional rescue assay demonstrated that the co-administration of TRP and the PI3K activator 740Y-P effectively reversed the impact of TRP on the phenotypes of OSCC cells. Conversely, the combination of TRP and the PI3K inhibitor LY294002 further enhanced the effect of TRP on the phenotypes of OSCC cells. Remarkably, treatment with TRP in zebrafish xenograft models demonstrated a significant reduction in both tumor growth and metastatic spread. CONCLUSIONS: Triphala exerted significant inhibitory effects on cell metabolic activity, migration, invasion, and proliferation in OSCC cell lines, accompanied by the induction of apoptosis, which was mediated through the inactivation of the PI3K/Akt pathway.

Controllable Adaptive Molybdate-Oligosaccharide Nanoparticles Regulate M2 Macrophage Mitochondrial Function and Promote Angiogenesis via PI3K/HIF-1α/VEGF Pathway to Accelerate Diabetic Wound Healing.

The complex wound environment of diabetic wounds leads to poor treatment efficacy, and the inflammatory disorders and vascular injury are the primary causes of death in such patients. Herein, a sprayable, controllable adaptive, pH-responsive nanosystem of molybdate and oligosaccharide (CMO) is specially developed as an immunomodulatory and angiogenesis-promotion material for diabetic wound healing. CMO exhibited pH-responsive release of Mo2+ and oligosaccharide (COS), specifically in response to the alkalescent environment observed in diabetic wounds. CMO provide an anti-inflammatory environment by promoting M2 polarization through significantly stimulating macrophage mitochondrial function. Specifically, CMO with a certain concentration reduce reactive oxygen species (ROS) and tumor necrosis factor α (TNF-α) expression, and upregulated mitochondrial membrane potential (MMP), superoxide dismutase (SOD), and interleukin 10 (IL-10) expression in macrophages. Moreover, CMO facilitate angiogenesis via upregulating the PI3K/HIF-1α/VEGF pathway-a critical process for the formation of new blood vessels that supply nutrients and oxygen to the healing tissue. Remarkably, CMO promote cell viability and migration of endothelial cells, and enhance the expression of angiogenic genes. In vitro and in vivo studies suggest this simple but powerful nanosystem targeting mitochondrial function has the potential to become an effective treatment for diabetic wound healing.

A novel image deep learning-based sub-centimeter pulmonary nodule management algorithm to expedite resection of the malignant and avoid over-diagnosis of the benign.

OBJECTIVES: With the popularization of chest computed tomography (CT) screening, there are more sub-centimeter (≤ 1 cm) pulmonary nodules (SCPNs) requiring further diagnostic workup. This area represents an important opportunity to optimize the SCPN management algorithm avoiding "one-size fits all" approach. One critical problem is how to learn the discriminative multi-view characteristics and the unique context of each SCPN. METHODS: Here, we propose a multi-view coupled self-attention module (MVCS) to capture the global spatial context of the CT image through modeling the association order of space and dimension. Compared with existing self-attention methods, MVCS uses less memory consumption and computational complexity, unearths dimension correlations that previous methods have not found, and is easy to integrate with other frameworks. RESULTS: In total, a public dataset LUNA16 from LIDC-IDRI, 1319 SCPNs from 1069 patients presenting to a major referral center, and 160 SCPNs from 137 patients from three other major centers were analyzed to pre-train, train, and validate the model. Experimental results showed that performance outperforms the state-of-the-art models in terms of accuracy and stability and is comparable to that of human experts in classifying precancerous lesions and invasive adenocarcinoma. We also provide a fusion MVCS network (MVCSN) by combining the CT image with the clinical characteristics and radiographic features of patients. CONCLUSION: This tool may ultimately aid in expediting resection of the malignant SCPNs and avoid over-diagnosis of the benign ones, resulting in improved management outcomes. CLINICAL RELEVANCE STATEMENT: In the diagnosis of sub-centimeter lung adenocarcinoma, fusion MVCSN can help doctors improve work efficiency and guide their treatment decisions to a certain extent. KEY POINTS: • Advances in computed tomography (CT) not only increase the number of nodules detected, but also the nodules that are identified are smaller, such as sub-centimeter pulmonary nodules (SCPNs). • We propose a multi-view coupled self-attention module (MVCS), which could model spatial and dimensional correlations sequentially for learning global spatial contexts, which is better than other attention mechanisms. • MVCS uses fewer huge memory consumption and computational complexity than the existing self-attention methods when dealing with 3D medical image data. Additionally, it reaches promising accuracy for SCPNs' malignancy evaluation and has lower training cost than other models.

Dynamic monitoring of serum tumor markers as prognostic factors in patients with advanced non-small-cell lung cancer treated with first-line immunotherapy: a multicenter retrospective study.

Background: To date, no specific studies have reported the use of dynamic serum tumor markers (STMs) as prognostic factors in patients with advanced non-small-cell lung cancer (NSCLC) who receive first-line immunotherapy. Therefore, it is unclear whether STMs can be used as a prognostic factor for first-line immunotherapy in advanced NSCLC. Objectives: To elucidate the role of STMs in monitoring immunotherapy response in advanced NSCLC. Patients were treated with first-line programmed cell death-1/programmed cell death ligand-1 inhibitors at four Chinese centers. Design: This was a multicenter retrospective study. Methods: Blood samples were collected at baseline and after 6-8 weeks of treatment. Computed tomography scans were used to evaluate treatment efficacy according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Post-treatment drops in STMs [Serum carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin fragment 19 (CYFRA21-1), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125)] were decreased ⩾20% (Group C) over baseline was used as cutoff level for defining a marker response. If STMs were increased by ⩾20% after treatment, the therapeutic effect was limited (Group A). Patients with STM changes between a 20% increase or decrease were enrolled in Group B. In univariate and multivariate stepwise Cox regression analyses, STMs and RECIST responses were analyzed for their impact on progression-free survival (PFS) and overall survival (OS). Results: The analysis included 716 patients. By multivariate analysis, CEA, NSE, CYFRA21-1, CA19-9, and CA125 (Group A versus Group B and Group A versus Group C) were associated with significant differences in PFS. Similar results were observed in the OS analysis. Similar results were observed in the adenocarcinoma subgroup analyses. In squamous cell carcinoma subgroup analyses, there was no statistical difference in PFS (p = 0.147) or OS (p = 0.068) between Group A and Group B for CA125. Conclusion: The increase and decrease in serum levels of STMs might be reliable prognostic factors for immunotherapy efficacy in NSCLC patients.

The genes regulating sensitivity of tumor cells to T cell-mediated killing: could they be potential personalized immunotherapeutic targets in head and neck squamous cell carcinoma?

OBJECTIVE: To identify the pivotal genes, specifically the STTK genes, that govern the sensitivity of tumor cells to T cell-mediated killing in Head and Neck Squamous Cell Carcinoma (HNSC). METHODS: The differentially expressed genes (DEGs) in HNSC and STTK genes were overlapped to obtain the DE-STTK genes. Univariate and LASSO regression analyses were conducted to identify the pivotal DE-STTK genes that serve as hubs in HNSC (i.e., hub DE-STTK genes). The risk model was established to divide HNSC tumor samples into high- and low-risk groups based on the hub DE-STTK genes. Further investigations were carried out by examing the expression level, prognostic values, diagnostic values, enriched signaling pathways, correlation with tumor mutation burden (TMB), and association with tumor immune infiltration cells (TIICs). RESULTS: A total of 71 genes were found to be overlapped between DEGs in HNSC and STTK genes. Lasso regression analysis identified 9 hub genes which were MYF6, AATF, AURKA, CXCL9, DPM2, MYO1B, NCBP2, TNFRSF12A, and TRAF1. The network analysis of hub DE-STTK genes-pathway reveals that these 9 hub genes exhibit enrichment in multiple signaling pathways, including toll-like receptor signaling, TNF signaling, NF-kappa B signaling, cytokine-cytokine receptor interaction, spliceosome, mRNA surveillance pathway, nucleocytoplasmic transport, GPI-anchor biosynthesis, as well as N-Glycan biosynthesis. The Pearson correlation analysis showed that the majority of correlations between 9 hub DE-STTK genes and immune cells were positive. CONCLUSION: The 9 identified hub DE-STTK genes (MYF6, AATF, AURKA, CXCL9, DPM2, MYO1B, NCBP2, TNFRSF12A, and TRAF1) are presumptively implicated in the modulation of tumor immunity in HNSC. These genes, along with their enriched pathways, hold promise as potential personalized immunotherapeutic targets for the treatment of HNSC, thereby offering novel avenues for therapeutic intervention in this malignancy.

Baseline serum tumor markers predict the survival of patients with advanced non-small cell lung cancer receiving first-line immunotherapy: a multicenter retrospective study.

BACKGROUND: This study aimed to investigate the association between baseline serum tumor markers (STMs) (carcinoembryonic antigen [CEA], neuron-specific enolase [NSE], cytokeratin-19 fragment [CYFRA21-1], carbohydrate antigen 19-9 [CA19-9], and carbohydrate antigen 125 [CA125]) and the efficacy of first-line immunotherapy in patients with advanced non-small cell lung cancer. METHODS: This multicenter retrospective study evaluated patients who received first-line immunotherapy between July 2017 and July 2022. The endpoints were progression-free survival (PFS) and overall survival (OS), as defined by the Response Evaluation Criteria in Solid Tumors version 1.1. We divided the patients into three groups based on STM levels: Group A ≥ threefold upper limit of normal, threefold upper limit of normal > Group B > upper limit of normal, and Group C ≤ upper limit of normal. RESULTS: In total, 716 patients were included in this study. In Cox proportional hazards analyses, the STM levels in Group C were independently associated with superior PFS and OS in patients with lung adenocarcinoma (LUAD). Except for CA19-9 level, the STM levels in Group C were independently associated with superior PFS and OS in patients with lung squamous carcinoma (LUSC). Except for CEA and CA19-9 levels, the levels in Group A were independently associated with inferior PFS and OS in patients with LUAD and LUSC. CONCLUSIONS: Serum CEA, NSE, CYFRA21-1, and CA125 levels can predict PFS and OS in patients with LUAD and LUSC, and serum CA19-9 levels can predict PFS and OS in patients with LUAD. The higher the serum NSE, CYFRA21-1, and CA125 levels, the worse the PFS and OS in patients with LUAD and LUSC. In addition, the higher the serum CA19-9 level, the worse the OS in patients with LUAD.

Studying trabecular bone samples demonstrates a power law relation between deteriorated structure and mechanical properties - a study combining 3D printing with the finite element method.

Introduction: The bone volume fraction (BV/TV) significantly contributes to the mechanical properties of trabecular bone. However, when studies compare normal trabeculae against osteoporotic trabeculae (in terms of BV/TV decrease), only an "average" mechanical result has been determined because of the limitation that no two trabecular structures are the same and that each unique trabecular structure can be mechanically tested only once. The mathematic relation between individual structural deterioration and mechanical properties during aging or the osteoporosis process has yet to be further clarified. Three-dimensional (3D) printing and micro-CT-based finite element method (µFEM) can assist in overcoming this issue. Methods: In this study, we 3D printed structural-identical but BV/TV value-attenuated trabecular bones (scaled up ×20) from the distal femur of healthy and ovariectomized rats and performed compression mechanical tests. Corresponding µFEM models were also established for simulations. The tissue modulus and strength of 3D printed trabecular bones as well as the effective tissue modulus (denoted as Ez) derived from µFEM models were finally corrected by the side-artifact correction factor. Results: The results showed that the tissue modulus corrected, strength corrected and Ez corrected exhibited a significant power law function of BV/TV in structural-identical but BV/TV value-attenuated trabecular samples. Discussion: Using 3D printed bones, this study confirms the long-known relationship measured in trabecular tissue with varying volume fractions. In the future, 3D printing may help us attain better bone strength evaluations and even personal fracture risk assessments for patients who suffer from osteoporosis.

Microleakage, microgap, and shear bond strength of an infiltrant for pit and fissure sealing.

Objectives: This study aimed to evaluate the potential clinical application of an infiltrant with different etchants as pit and fissure sealants and to compare them with a conventional resin-based sealant. Materials and methods: Seventy-five molars were randomly divided into three groups (n = 25): phosphoric acid etchant + conventional resin-based sealant (Group A); 15% hydrochloric acid etchant + infiltrant (Group B); phosphoric acid etchant + infiltrant (Group C). Fifteen teeth in each group were subjected to pit and fissure sealing procedures. After 500 thermocycling and methylene blue dye penetration, ten specimens were sectioned and the pencentages of dye penetration were measured under a stereomicroscope. Another five teeth in each group were sectioned and the microgaps between materials and enamel surface were measured using electron microscope scanning. Ten teeth in each group were used to measure shear bond strength and the failure mode was analyzed. Results: The results showed that infiltrant exhibited significantly less microleakage and microgap than resin-based sealant, no matter which echant was used. Although there was no significant difference betweern the three groups, infiltrant applied with 15% hydrochloric acid etching showed higher shear bond strength than resin-based sealant etching with 35% phosphoric acid. Conclusions: The infiltrant has significant advantages in reducing the degree of microleakage and microgap. Moreover, the infiltrant could achieve the same bonding strength as conventional resin-based sealant. Although, manufacturers do not currently recommend the infiltrant for fissure sealing, the potential clinical application would be an off-label use.Clinical relevance This report provides a theoretical basis for the potential clinical application of the infiltrant as a pit and fissure sealant, and provides a new perspective for selecting pit and fissure sealants.

Combined computational analysis and cytology show limited depth osteogenic effect on bone defects in negative pressure wound therapy.

Background: The treatment of bone defects remains a clinical challenge. The effect of negative pressure wound therapy (NPWT) on osteogenesis in bone defects has been recognized; however, bone marrow fluid dynamics under negative pressure (NP) remain unknown. In this study, we aimed to examine the marrow fluid mechanics within trabeculae by computational fluid dynamics (CFD), and to verify osteogenic gene expression, osteogenic differentiation to investigate the osteogenic depth under NP. Methods: The human femoral head is scanned using micro-CT to segment the volume of interest (VOI) trabeculae. The VOI trabeculae CFD model simulating the bone marrow cavity is developed by combining the Hypermesh and ANSYS software. The effect of trabecular anisotropy is investigated, and bone regeneration effects are simulated under NP scales of -80, -120, -160, and -200 mmHg. The working distance (WD) is proposed to describe the suction depth of the NP. Finally, gene sequence analysis, cytological experiments including bone mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation are conducted after the BMSCs are cultured under the same NP scale. Results: The pressure, shear stress on trabeculae, and marrow fluid velocity decrease exponentially with an increase in WD. The hydromechanics of fluid at any WD inside the marrow cavity can be theoretically quantified. The NP scale significantly affects the fluid properties, especially those fluid close to the NP source; however, the effect of the NP scale become marginal as WD deepens. Anisotropy of trabecular structure coupled with the anisotropic hydrodynamic behavior of bone marrow; An NP of -120 mmHg demonstrates the majority of bone formation-related genes, as well as the most effective proliferation and osteogenic differentiation of BMSCs compared to the other NP scales. Conclusion: An NP of -120 mmHg may have the optimal activated ability to promote osteogenesis, but the effective WD may be limited to a certain depth. These findings help improve the understanding of fluid mechanisms behind NPWT in treating bone defects.

The oral microbiome in autoimmune diseases: friend or foe?

The human body is colonized by abundant and diverse microorganisms, collectively known as the microbiome. The oral cavity has more than 700 species of bacteria and consists of unique microbiome niches on mucosal surfaces, on tooth hard tissue, and in saliva. The homeostatic balance between the oral microbiota and the immune system plays an indispensable role in maintaining the well-being and health status of the human host. Growing evidence has demonstrated that oral microbiota dysbiosis is actively involved in regulating the initiation and progression of an array of autoimmune diseases.Oral microbiota dysbiosis is driven by multiple factors, such as host genetic factors, dietary habits, stress, smoking, administration of antibiotics, tissue injury and infection. The dysregulation in the oral microbiome plays a crucial role in triggering and promoting autoimmune diseases via several mechanisms, including microbial translocation, molecular mimicry, autoantigen overproduction, and amplification of autoimmune responses by cytokines. Good oral hygiene behaviors, low carbohydrate diets, healthy lifestyles, usage of prebiotics, probiotics or synbiotics, oral microbiota transplantation and nanomedicine-based therapeutics are promising avenues for maintaining a balanced oral microbiome and treating oral microbiota-mediated autoimmune diseases. Thus, a comprehensive understanding of the relationship between oral microbiota dysbiosis and autoimmune diseases is critical for providing novel insights into the development of oral microbiota-based therapeutic approaches for combating these refractory diseases.

Analysis of epidemiological trends of and associated factors for tooth loss among 35- to 44-year-old adults in Guangdong, Southern China, 1995-2015: a population-based cross-sectional survey.

BACKGROUND: Tooth loss is a known marker of oral and systemic health, but large-scale population-based and cross-sectional multi-year comparative studies on tooth loss have yet to be much studied in China. This study explores the changing trends in tooth loss status and the associated factors influencing the prevalence of tooth loss over the past two decades in Guangdong, Southern China. METHODS: Data from three cross-sectional, representative oral epidemiological surveys in Guangdong Province were analyzed, including 400 in 1995, 720 in 2005, and 288 in 2015, for a total of 1408 participants. Sample selection is based on the National Census of China published by the National Bureau of Statistics. In this study, each year, the number of missing teeth (MT) and the prevalence of tooth loss (MT > 0) were calculated. Basic demographic information, socioeconomic status, caries and periodontal status, personal lifestyle factors, and dental health care behaviors were analyzed by multivariate logistic regression to estimate their associations with tooth loss. Statistical significance was evaluated with 2-sided tests with a significance level of P < 0.05. RESULTS: This study found that the mean number of missing teeth and the prevalence of tooth loss among adults aged 35-44 years in Guangdong Province did not change significantly in the first decade (1995-2005) but decreased significantly in the second decade (2005-2015) (0.94 and 40.8% in 1995, 0.99 and 42.9% in 2005, and 0.63 and 33.3% in 2015, respectively). The mean number of MT by tooth position was highest for the first and second molars, and both were larger in the mandible than in the maxilla. In 1995, populations with low educational attainment and the presence of caries or periodontal pocket (periodontal probing depth ≥ 4 mm) were associated with a higher chance of MT > 0. In 2005, those with low educational attainment, the presence of caries, and 40-44 years old were associated with a higher chance of MT > 0. Moreover, in 2015, females, rural residents, and those with caries or periodontal pocket were associated with a higher chance of MT > 0. CONCLUSIONS: Although tooth retention has improved recently (2005-2015) and the preventive effect of education level on tooth loss has increased over time, efforts to prevent tooth loss in adults need to be strengthened. Particular attention should be given to preventive interventions for women, rural residents, and those suffering from caries or periodontal pocket.

3D printed trabeculae conditionally reproduce the mechanical properties of the actual trabeculae - A preliminary study.

Three-dimensional (3D) printing has been used to fabricate synthetic trabeculae models and to test mechanical behavior that cannot be recognized in the actual sample, but the extent to which 3D printed trabeculae replicate the mechanical behavior of the actual trabeculae remains to be quantified. The aim of this study was to evaluate the accuracy of 3D printed trabeculae in reproducing the mechanical properties of the corresponding actual trabeculae. Twelve human trabecular cubes (5 × 5 × 5 mm) were scanned by micro-CT to form the trabecular 3D model. Each trabecular 3D model was scaled ×2-, ×3-, ×4- and ×5-fold and then printed twice at a layer thickness of 60 µm using poly (lactic acid) (PLA). The actual trabecular cubes and the 3D-printed trabecular cubes were first compressed under a loading rate of 1 mm/min; another replicated stack of 3D-printed trabecular cubes was compressed under a strain rate of 0.2/min. The results showed that the stiffness of the printed cubes tended to increase, while the strength tended to converge when the magnification increased under the two loading conditions. The strain rate effect was found in the printed cubes. The correlation coefficient (R2) of the mechanical properties between the printed and actual trabeculae can reach up to 0.94, especially under ×3-, ×4- and ×5-fold magnification. In conclusion, 3D printing could be a potential tool to evaluate the mechanical behavior of actual trabecular tissue in vitro and may help in the future to predict the risk of fracture and even personalize the treatment evaluation for osteoporosis and other trabecular bone pathologies.

Identifying crosstalk genetic biomarkers linking a neurodegenerative disease, Parkinson's disease, and periodontitis using integrated bioinformatics analyses.

Objective: To identify the genetic linkage mechanisms underlying Parkinson's disease (PD) and periodontitis, and explore the role of immunology in the crosstalk between both these diseases. Methods: The gene expression omnibus (GEO) datasets associated with whole blood tissue of PD patients and gingival tissue of periodontitis patients were obtained. Then, differential expression analysis was performed to identify the differentially expressed genes (DEGs) deregulated in both diseases, which were defined as crosstalk genes. Inflammatory response-related genes (IRRGs) were downloaded from the MSigDB database and used for dividing case samples of both diseases into different clusters using k-means cluster analysis. Feature selection was performed using the LASSO model. Thus, the hub crosstalk genes were identified. Next, the crosstalk IRRGs were selected and Pearson correlation coefficient analysis was applied to investigate the correlation between hub crosstalk genes and hub IRRGs. Additionally, immune infiltration analysis was performed to examine the enrichment of immune cells in both diseases. The correlation between hub crosstalk genes and highly enriched immune cells was also investigated. Results: Overall, 37 crosstalk genes were found to be overlapping between the PD-associated DEGs and periodontitis-associated DEGs. Using clustering analysis, the most optimal clustering effects were obtained for periodontitis and PD when k = 2 and k = 3, respectively. Using the LASSO feature selection, five hub crosstalk genes, namely, FMNL1, MANSC1, PLAUR, RNASE6, and TCIRG1, were identified. In periodontitis, MANSC1 was negatively correlated and the other four hub crosstalk genes (FMNL1, PLAUR, RNASE6, and TCIRG1) were positively correlated with five hub IRRGs, namely, AQP9, C5AR1, CD14, CSF3R, and PLAUR. In PD, all five hub crosstalk genes were positively correlated with all five hub IRRGs. Additionally, RNASE6 was highly correlated with myeloid-derived suppressor cells (MDSCs) in periodontitis, and MANSC1 was highly correlated with plasmacytoid dendritic cells in PD. Conclusion: Five genes (i.e., FMNL1, MANSC1, PLAUR, RNASE6, and TCIRG1) were identified as crosstalk biomarkers linking PD and periodontitis. The significant correlation between these crosstalk genes and immune cells strongly suggests the involvement of immunology in linking both diseases.

Retraction Notice to: MTTL3 upregulates microRNA-1246 to promote occurrence and progression of NSCLC via targeting paternally expressed gene 3.

[This retracts the article DOI: 10.1016/j.omtn.2021.02.020.].

Oral health-related quality of life in patients with osteoarthritis of the temporomandibular joint-Results of a systematic review.

OBJECTIVES: The aim of this systematic review was to assess the oral health-related quality of life (OHRQoL) of patients with osteoarthritis (OA) of the temporomandibular joint (TMJ). METHODS: This systematic literature search applied the search terms "oral health-related quality of life AND osteoarthritis of jaw OR arthritis of temporomandibular joint AND oral health-related quality of life" in PubMed, Medline, Web of Science and Scopus. Eligibility criteria were publication until 31 August 2021, examination of children or adults with OA of TMJ, reporting of any OHRQoL measurement and a full text in English language. Two different, independent and experienced reviewers performed this systematic literature search. The analysis of respective data was qualitative. For quality appraisal, the available checklist from the Agency for Healthcare Research and Quality (AHRQ) was applied. RESULTS: Out of 102 findings, eight studies were included in qualitative analysis. Seven clinical investigations were performed in adults aged between 34 and 43 years. The other included study was performed on children. The quality of two studies was moderate, and six studies were evaluated as of high quality. Most studies applied the 14-item short form of the oral health impact profile (OHIP 14) for assessment of OHRQoL. OHIP 14 ranged between 9.24 and 38.86 points in means of sum score. Comparison with healthy individuals revealed worse OHRQoL of OA patients in two studies. Associations between OHRQoL with either oral health, general quality of life or disease-related parameters were rarely reported and heterogeneous. Five of the included studies reported subscales of OHIP 14, showing an impairment in all subscales. CONCLUSIONS: There are hints that patients with OA of the TMJ show a reduced OHRQoL. More studies are needed, especially regarding oral health, disease-related parameters and pain intensity and its potential influence on OHRQoL.

Identification of Key Pyroptosis-Related Genes and Distinct Pyroptosis-Related Clusters in Periodontitis.

Aim: This study aims to identify pyroptosis-related genes (PRGs), their functional immune characteristics, and distinct pyroptosis-related clusters in periodontitis. Methods: Differentially expressed (DE)-PRGs were determined by merging the expression profiles of GSE10334, GSE16134, and PRGs obtained from previous literatures and Molecular Signatures Database (MSigDB). Least absolute shrinkage and selection operator (LASSO) regression was applied to screen the prognostic PRGs and develop a prognostic model. Consensus clustering was applied to determine the pyroptosis-related clusters. Functional analysis and single-sample gene set enrichment analysis (ssGSEA) were performed to explore the biological characteristics and immune activities of the clusters. The hub pyroptosis-related modules were defined using weighted correlation network analysis (WGCNA). Results: Of the 26 periodontitis-related DE-PRGs, the highest positive relevance was for High-Mobility Group Box 1 (HMGB1) and SR-Related CTD Associated Factor 11 (SCAF11). A 14-PRG-based signature was developed through the LASSO model. In addition, three pyroptosis-related clusters were obtained based on the 14 prognostic PRGs. Caspase 3 (CASP3), Granzyme B (GZMB), Interleukin 1 Alpha (IL1A), IL1Beta (B), IL6, Phospholipase C Gamma 1 (PLCG1) and PYD And CARD Domain Containing (PYCARD) were dysregulated in the three clusters. Distinct biological functions and immune activities, including human leukocyte antigen (HLA) gene expression, immune cell infiltration, and immune pathway activities, were identified in the three pyroptosis-related clusters of periodontitis. Furthermore, the pink module associated with endoplasmic stress-related functions was found to be correlated with cluster 2 and was suggested as the hub pyroptosis-related module. Conclusion: The study identified 14 key pyroptosis-related genes, three distinct pyroptosis-related clusters, and one pyroptosis-related gene module describing several molecular aspects of pyroptosis in the pathogenesis and immune micro-environment regulation of periodontitis and also highlighted functional heterogeneity in pyroptosis-related mechanisms.

Comparison of Immunotherapy, Chemotherapy, and Chemoimmunotherapy in Advanced Pulmonary Lymphoepithelioma-Like Carcinoma： A Retrospective Study.

Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare subtype of lung cancer that is associated with the Epstein-Barr virus in Asia. Due to the lack of prospective studies, the best first-line treatment and survival outcomes remain unclear. Herein, This study investigated the efficacy and safety of different treatment regimens for advanced pLELC. This retrospective study included 68 patients with advanced pLELC from two centers in China. Patients were divided into three groups according to different first-line treatments: chemotherapy (n=49, 72.1%), immunotherapy (n=7, 10.3%), and chemoimmunotherapy (n=12,17.6%). The primary endpoint of this study was the 2-year progression-free survival (PFS) of each group. The results show that the median PFS was 6.9 months (range, 2.3-not estimable) in the chemotherapy group, 11.0 months (range, 2-not estimable) in the immunotherapy group, and 11.8 months (range, 6-not estimable) in the chemoimmunotherapy group. There was a significant difference in 2-year PFS between the chemoimmunotherapy group and the chemotherapy group (hazard ratio, 0.38, 95% confidence interval: 0.18-0.78, log-rank P=0.007). The most frequent grade 3-4 adverse event in the chemotherapy and chemoimmunotherapy groups was myelosuppression (10/49 [22.4%] and 4/12 [33.3%], respectively). The most frequent grade 3-4 adverse events in the immunotherapy group were diarrhea (1/7, 14.8%) and hepatotoxicity (1/7, 14.8%). Chemoimmunotherapy had the highest 2-year PFS as a first-line treatment for advanced pLELC compared to chemotherapy and immunotherapy. This study suggests that chemoimmunotherapy may be the best first-line treatment for patients with advanced pLELC.

Metagenomic and Metatranscriptomic Insight Into Oral Biofilms in Periodontitis and Related Systemic Diseases.

The oral microbiome is one of the most complex microbial communities in the human body and is closely related to oral and systemic health. Dental plaque biofilms are the primary etiologic factor of periodontitis, which is a common chronic oral infectious disease. The interdependencies that exist among the resident microbiota constituents in dental biofilms and the interaction between pathogenic microorganisms and the host lead to the occurrence and progression of periodontitis. Therefore, accurately and comprehensively detecting periodontal organisms and dissecting their corresponding functional activity characteristics are crucial for revealing periodontitis pathogenesis. With the development of metagenomics and metatranscriptomics, the composition and structure of microbial communities as well as the overall functional characteristics of the flora can be fully profiled and revealed. In this review, we will critically examine the currently available metagenomic and metatranscriptomic evidence to bridge the gap between microbial dysbiosis and periodontitis and related systemic diseases.

Greater inequalities in dental caries treatment than in caries experience: a concentration index decomposition approach.

BACKGROUND: The aim of the current study was to (a) measure the socioeconomic inequalities in oral health and examine whether the inequalities are greater in disease experience or in its treatment and to (b) decompose the factors that influence oral health inequalities among the adults of Guangdong Province. METHODS: A cross-sectional study was conducted among 35- to 44-year-old and 65- to 74-year-old adults in Guangdong Province. All participants underwent oral health examinations and answered questionnaires about their oral health. We measured the concentration indices of the DMFT and its separate components, namely, decayed teeth (DT), missing teeth (MT), and filled teeth (FT), to explore the inequalities in oral health status; then, we analysed its decomposition to interpret the factors that influence the inequalities. RESULTS: The results showed that significant inequality was concentrated on FT (CI = 0.24, 95% CI = 0.14/0.33, SE = 0.05). The concentration indices for the DMFT (CI = 0.02, 95% CI = 0.02/0.06, SE = 0.02) and MT (CI = 0.02, 95% CI 0.03/0.08, SE = 0.03) were small and close to zero, while the concentration for DT (CI = - 0.04, 95% CI = - 0.01/0.02, SE = 0.03) was not statistically significant. The results from the decomposition analysis suggested that a substantial proportion of the inequality was explained by household income, high education level, regular oral examination and type of insurance (5.1%, 12.4%, 43.2%, - 39.6% (Urban Employee Basic Medical Insurance System) and 34.5% (New-Type Rural Medical Collaboration System), respectively). CONCLUSIONS: The results indicated greater inequalities in dental caries than in caries experience. Among the included factors, household income, high education level, and regular oral health examinations had the greatest impact on the inequalities in the number of FT. In addition, the current medical insurance systems, including the Urban Employee Basic Medical Insurance System, Urban Resident Basic Medical Insurance System, and the New-Type Rural Medical Collaboration System, have not been effectively used in oral treatment. Policy-making and the implementation of interventions for tackling socioeconomic oral health inequalities should focus on reducing the burden of treatment and providing greater access to dental care for low-income groups. Welfare policies are skewed towards rural areas and low-income people.

Survival rates of patients with tumors originating in different segments of the left upper lung in stage I to III non-small cell lung cancer.

BACKGROUND: The aim of this research was to evaluate the effect of spatial location of tumors on the prognosis of patients with left upper lung non-small cell lung cancer (NSCLC), with a focus on the S1+2+3 and lingual segment. METHODS: A total of 486 patients who underwent lobectomy and systematic lymph node dissection were collected retrospectively in this study (354 S1+2+3 and 132 lingual segment patients). Factors impacting survival were assessed via univariate analyses, multivariate analyses, and log-rank tests. RESULTS: Compared with tumor location in S1+2+3, lingual segment tumor location of stage II to III left upper lung NSCLC patients was significantly associated with a better 5-year disease-free survival (DFS) (P=0.041). Multivariate analysis results showed that tumor location in the lingual segment was a good independent prognostic factor of stage II to III left upper lung NSCLC patients [hazard ratio (HR) =0.602, 95% confidence interval (CI): 0.149-0.865, P=0.006). However, in stage I left upper lung NSCLC, tumor location (HR =1.069, 95% CI: 0.571-2.000, P=0.835) was not an independent prognostic factor, and only T2 (HR =2.422, 95% CI: 1.271-4.620, P=0.007) was an independent worse prognosis factor. CONCLUSIONS: Tumor location in the lingual segment of left upper lung stage II to stage III NSCLC is a good independent prognostic factor compared with S1+2+3. Nevertheless, tumor location does not impact the prognosis of patients with stage I NSCLC in the left upper lung.