Evaluation of tracheal diameter and angles in fetuses with double aortic arch using prenatal ultrasound: implications for postnatal management.

Objective: This study aims to analyze the value of prenatal ultrasound in the screening, diagnosis, and treatment of double aortic arch (DAA) malformations. Methods: A retrospective analysis was conducted on 31 fetal cases with double aortic arch anomalies over a 12-year period from June 1, 2011 to June 1, 2023. The assessment included combined measurements of fetal tracheal internal diameter Z-score and DAA pinch angle, along with ultrasonographic findings, associated anomalies, genetic abnormalities, postnatal CTA images, and long-term postnatal outcomes. Results: Of the 31 fetal double aortic arch cases, 15 were right aortic arch dominant, 2 were left aortic arch dominant, and 14 had a balanced double arch. Genetic testing was performed on 19 cases, revealing abnormalities in 2 cases, including one Turner syndrome, and one carrier of ichthyosis gene with heterozygous deletion. Out of the total cases, 29 were delivered, and 2 cases were terminated. Prenatal diagnosis accurately identified 29 cases (29/31, 93.5%), which was confirmed by postnatal pathological anatomy, echocardiography, surgery or CTA. Fetal tracheal internal diameter Z-scores were significantly smaller in the symptomatic group than in the asymptomatic group (-1.27 ± 0.49 vs -0.68 ± 0.60, P = 0.018). The area under the curve was 0.776 (95% confidence interval, 0.593-0.960) using a tracheal internal diameter z-score cutoff of -0.73 with a sensitivity of 90% and specificity of 64.7%. The double arch pinch angle was significantly smaller in the symptomatic group than in the asymptomatic group [52.50° (38.25° to 59.00°) vs 60.00° (53.50° to 70.50°), P = 0.035]. The area under the curve was 0.744 (95% confidence interval, 0.554-0.935), and the sensitivity for determining the presence or absence of symptoms was 90% when the cutoff value was 62.5°, with a specificity of 47.1%. Fifteen cases opted for surgery with favorable surgical outcome. Conclusion: Prenatal echocardiography demonstrates good diagnostic efficacy for fetal double aortic arch. It is also essential to detect the presence of other underlying intra- and extracardiac malformations and genetic abnormalities. There is a significant difference in prenatal tracheal internal diameter Z-scores and double arch pinch angle between asymptomatic and symptomatic DAA infants. Symptomatic infants require early surgery, while asymptomatic infants should be monitored.

Association of multiple trace metals in scalp hair with glioma risk: the mediating role of inflammation.

OBJECTIVE: To explore the relationship between 35 trace metals in scalp hair and the glioma risk as well as the potential mediating roles of 27 plasma inflammatory cytokines. METHODS: A case-control study involving 228 participants was performed in southeastern China. Trace metals in scalp hair were analyzed using inductively coupled plasma mass spectrometry, and multiplex cytokines were detected based on Luminex® technology. The least absolute shrinkage and selection operator (LASSO) regression in combination with four machine learning methods were used to select trace metals associated with gliomas. The joint exposure effect of trace metals was estimated using the generalized weighted quantile sum (gWQS) regression and quantile-based g-computation (qgcomp) algorithms. RESULTS: Both LASSO regression and random forest algorithms identified five trace metals (gadolinium [Gd], lithium [Li], thulium [Tm], thorium [Th], and molybdenum [Mo]) associated with gliomas. After adjustments for potential confounders, Gd (odds ratio [OR] = 2.84, 95% confidence interval [CI]: 1.89-4.43) and Li (OR = 1.77, 95% CI: 1.04-3.02) concentrations were positively associated with glioma risk, while Tm (OR = 0.36, 95% CI: 0.17-0.73) and Th (OR = 0.45, 95% CI: 0.28-0.71) exhibited inverse associations. Both gWQS and qgcomp algorithms showed Gd contributed most to the mixture effect. Moreover, there was a significant interaction between Gd and Tm or Th on glioma risk (p < 0.05). Notably, granulocyte-macrophage colony-stimulating factor (GM-CSF) mediated the association between Gd exposure and glioma risk by 25.75%. INTERPRETATION: These findings suggest potential associations of certain trace metals, especially for Gd, with glioma risk, and may provide new insights into the mechanisms underlying from an inflammatory response perspective.

The potential value of oral microbial signatures for prediction of oral squamous cell carcinoma based on machine learning algorithms.

OBJECTIVE: This study aimed to explore the potential predictive value of oral microbial signatures for oral squamous cell carcinoma (OSCC) risk based on machine learning algorithms. METHODS: The oral microbiome signatures were assessed in the unstimulated saliva samples of 80 OSCC patients and 179 healthy individuals using 16S rRNA gene sequencing. Four different machine learning classifiers were used to develop prediction models. RESULTS: Compared with control participants, OSCC patients had a higher microbial dysbiosis index (MDI, p < 0.001). Among four machine learning classifiers, random forest (RF) provided the best predictive performance, followed by the support vector machines, artificial neural networks and naive Bayes. After controlling the potential confounders using propensity score matching, the optimal RF model was further developed incorporating a minimal set of 20 bacteria genera, exhibiting better predictive performance than the MDI (AUC: 0.992 vs. 0.775, p < 0.001). CONCLUSIONS: The novel MDI and RF model developed in this study based on oral microbiome signatures may serve as noninvasive tools for predicting OSCC risk.

Pyroptotic macrophages induce disruption of glutamate metabolism in periodontal ligament stem cells contributing to their compromised osteogenic potential.

Macrophage pyroptosis is of key importance to host defence against pathogen infections and may participate in the progression and recovery of periodontitis. However, the role of pyroptotic macrophages in regulating periodontal ligament stem cells (PDLSCs), the main cell source for periodontium renewal, remains unclear. First, we found that macrophage pyroptosis were enriched in gingiva tissues from periodontitis patients compared with those of healthy people through immunofluorescence. Then the effects of pyroptotic macrophages on the PDLSC osteogenic differentiation were investigated in a conditioned medium (CM)-based coculture system in vitro. CM derived from pyroptotic macrophages inhibited the osteogenic differentiation-related gene and protein levels, ALP activity and mineralized nodule formation of PDLSCs. The osteogenic inhibition of CM was alleviated when pyroptosis was inhibited by VX765. Further, untargeted metabolomics showed that glutamate limitation may be the underlying mechanism. However, exogenous glutamate supplementation aggravated the CM-inhibited osteogenic differentiation of PDLSCs. Moreover, CM increased extracellular glutamate and decreased intracellular glutamate levels of PDLSCs, and enhanced the gene and protein expression levels of system xc - (a cystine/glutamate antiporter). After adding cystine to CM-based incubation, the compromised osteogenic potency of PDLSCs was rescued. Our data suggest that macrophage pyroptosis is related to the inflammatory lesions of periodontitis. Either pharmacological inhibition of macrophage pyroptosis or nutritional supplements to PDLSCs, can rescue the compromised osteogenic potency caused by pyroptotic macrophages.

Association of individual and combined exposures of 10 metals with periodontitis: Results from a large population-based study.

AIMS: To systematically investigate the association between individual and combined metal exposure and periodontitis. METHODS: Data encompassing complete periodontal examinations and metal detection in blood and urine samples were procured from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Three statistical methods, namely weighted logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression, were used to evaluate the independent and combined associations between metals and periodontitis. RESULTS: Elevated concentrations of blood cadmium (odds ratio [OR]: 1.73, 95% confidence interval [CI]: 1.15-2.61) and blood lead (OR: 1.17, 95 %CI: 1.02-1.34) exhibited a positive association with periodontitis, even after adjusting for potential confounding factors. The BKMR and WQS regression suggested that the co-exposure of metals was also positively associated with periodontitis. Moreover, estradiol and albumin were identified as potential mediators in the relationship between the WQS index of the 10 metals in blood and periodontitis explaining 25.36% and 2.02% of the relationship, respectively. Furthermore, generally consistent patterns of associations between metals and periodontitis and mediating roles of estrogen and albumin were observed after a series of sensitivity analyses. CONCLUSION: This study provides evidence of positive associations between elevated levels of cadmium, lead or metal mixture and periodontitis, which may be partially mediated by sex hormones and oxidative stress indicators.

Preoperative Serum Selenium Concentrations and Disease-Specific Survival in Patients With Oral Cancer: A Long-Term Follow-Up Study.

BACKGROUND: Serum selenium (Se) concentration has been reported to be associated with the incidence of oral cancer. The association between serum Se and long-term survival in oral cancer patients is still unclear. PURPOSE: The purpose of this study is to measure the association between serum Se and disease-specific survival (DSS). STUDY DESIGN, SETTING, AND SAMPLE: This was a single-center, prospective cohort study conducted at the First Affiliated Hospital of Fujian Medical University (Fujian Province, China) from September 2011 to December 2018. The inclusion criteria were patients with newly diagnosed primary oral cancer confirmed by histology. The exclusion criteria were patients with recurrent oral cancer or metastatic cancer. PREDICTOR VARIABLE: The predictor variable is the preoperative serum Se concentration measured using inductively coupled plasma-mass spectrometry. MAIN OUTCOME VARIABLE(S): The primary outcome variable is DSS calculated from the date of diagnosis to the date of death due to oral cancer or the end of follow-up, whichever occurred first. COVARIATES: The covariates were age, sex, occupation, education level, body mass index, surgery therapy, adjuvant therapy, tumor node metastasis stage, and pathological grading. ANALYSES: Kaplan-Meier survival analysis, Cox proportional hazards regression, and restricted cubic spline regression were utilized. P value < .05 was significant. RESULTS: The sample was composed of 235 subjects with a median age of 59 years (ranged from 20 to 80 years) and 142 (60.43%) were male. The median follow-up was 54.90 months (interquartile range: 35.47). Se levels were associated with DSS (unadjusted hazard ratio [HR] = 0.70; 95% confidence interval [CI]: 0.54-0.91) suggesting that higher levels of Se are associated with longer or improved DSS. After adjustment of age, sex, occupation, education level, residence, tumor node metastasis stage, pathological grading, surgery therapy, radiotherapy, and chemotherapy, patients with higher serum Se had a better DSS (aHR = 0.67; 95% CI: 0.49-0.92). Of note, we found that the association between serum Se and DSS was observed only in patients with radiotherapy (aHR = 0.49; 95% CI: 0.33-0.73). And the protective effect of radiotherapy on survival was only observed in patients with higher Se concentrations (aHR = 0.36; 95% CI: 0.20-0.63). Additionally, there was a multiplicative interaction between Se and radiotherapy on the prognosis of oral cancer patients (Pinteraction<0.01). CONCLUSION AND RELEVANCE: Our findings suggest that a high Se concentration might contribute to better DSS among oral cancer patients, and the effect may partly depend on radiotherapy treatment. Given these findings, additional research should focus on the role of Se in DSS among oral cancer patients and the interaction with radiotherapy.

Non-symmetric stapling of native peptides.

Stapling has emerged as a powerful technique in peptide chemistry. It enables precise control over peptide conformation leading to enhanced properties such as improved stability and enhanced binding affinity. Although symmetric stapling methods have been extensively explored, the field of non-symmetric stapling of native peptides has received less attention, largely as a result of the formidable challenges it poses - in particular the complexities involved in achieving the high chemo-selectivity and site-selectivity required to simultaneously modify distinct proteinogenic residues. Over the past 5 years, there have been significant breakthroughs in addressing these challenges. In this Review, we describe the latest strategies for non-symmetric stapling of native peptides, elucidating the protocols, reaction mechanisms and underlying design principles. We also discuss current challenges and opportunities this field offers for future applications, such as ligand discovery and peptide-based therapeutics.

Strategies for the Construction of Multicyclic Phage Display Libraries.

Peptide therapeutics have gained great interest due to their multiple advantages over small molecule and antibody-based drugs. Peptide drugs are easier to synthesize, have the potential for oral bioavailability, and are large enough to target protein-protein interactions that are undruggable by small molecules. However, two major limitations have made it difficult to develop novel peptide therapeutics not derived from natural products, including the metabolic instability of peptides and the difficulty of reaching antibody-like potencies and specificities. Compared to linear and disulfide-monocyclized peptides, multicyclic peptides can provide increased conformational rigidity, enhanced metabolic stability, and higher potency in inhibiting protein-protein interactions. The identification of novel multicyclic peptide binders can be difficult, however, recent advancements in the construction of multicyclic phage libraries have greatly advanced the process of identifying novel multicyclic peptide binders for therapeutically relevant protein targets. This review will describe the current approaches used to create multicyclic peptide libraries, highlighting the novel chemistries developed and the proof-of-concept work done on validating these libraries against different protein targets.

Development and validation of a model for the prediction of disease-specific survival in patients with oral squamous cell carcinoma: based on random survival forest analysis.

OBJECTIVE: To establish a model for predicting the disease-specific survival (DSS) of patients with oral squamous cell carcinoma (OSCC). METHODS: Patients diagnosed with OSCC from the Surveillance, Epidemiology, and End Results (SEER) database were enrolled and randomly divided into development (n = 14,495) and internal validation cohort (n = 9625). Additionally, a cohort from a hospital located in Southeastern China was utilized for external validation (n = 582). RESULTS: TNM stage, adjuvant treatment, surgery, tumor sites, age, grade, and gender were used for RSF model construction based on the development cohort. The effectiveness of the model was confirmed through time-dependent ROC curves in different cohorts. The risk score exhibited an almost exponential increase in the hazard ratio of death due to OSCC. In development, internal, and external validation cohorts, the prognosis was significantly worse for patients in groups with higher risk scores (all log-rank P < 0.05). CONCLUSION: Based on RSF, a high-performance prediction model for OSCC prognosis was created and verified in this study.

Prognostic value of pretreatment lymphocyte percentage in oral cancer: A prospective cohort study.

OBJECTIVE: To assess the prognostic role of pretreatment lymphocyte percentage (LY%) for patients with oral squamous cell carcinoma (OSCC). METHODS: A large-scale prospective cohort study between July 2002 and March 2021 was conducted. Propensity score-matched (PSM) analysis and inverse probability of treatment weighting (IPTW) analysis were performed to adjust for potential confounders. Using random survival forest (RSF), the relative importance of pretreatment LY% in prognosis prediction was also assessed. RESULTS: A total of 743 patients were enrolled and followed up (median: 2.75 years, interquartile range: 1.25-4.42 years). A high pretreatment LY% was significantly associated with better disease-specific survival of patients with OSCC (Hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.42, 0.84). The same tendency was observed in PSM (HR = 0.57, 95% CI: 0.38, 0.85) and IPTW analysis (HR = 0.57, 95% CI: 0.40, 0.82). RSF showed that LY% ranked the fifth among importance ranking of all prognostic factors. CONCLUSION: Pretreatment LY% showed a moderate predictive ability, suggesting it might be a valuable tool to predict prognosis for patients with OSCC.

A Cysteine-Directed Proximity-Driven Crosslinking Method for Native Peptide Bicyclization.

Efficient and site-specific modification of native peptides and proteins is desirable for synthesizing antibody-drug conjugates as well as for constructing chemically modified peptide libraries using genetically encoded platforms such as phage display. In particular, there is much interest in efficient multicyclization of native peptides due to the appeals of multicyclic peptides as therapeutics. However, conventional approaches for multicyclic peptide synthesis require orthogonal protecting groups or non-proteinogenic clickable handles. Herein, we report a cysteine-directed proximity-driven strategy for the constructing bicyclic peptides from simple natural peptide precursors. This linear to bicycle transformation initiates with rapid cysteine labeling, which then triggers proximity-driven amine-selective cyclization. This bicyclization proceeds rapidly under physiologic conditions, yielding bicyclic peptides with a Cys-Lys-Cys, Lys-Cys-Lys or N-terminus-Cys-Cys stapling pattern. We demonstrate the utility and power of this strategy by constructing bicyclic peptides fused to proteins as well as to the M13 phage, paving the way to phage display of novel bicyclic peptide libraries.

The role of rare earth elements and dietary intake in tongue cancer: a mediation analysis in southeast China.

Objective: The current research aimed to examine how dietary intake and rare earth elements may affect the development of tongue cancer. Methods: The serum levels of 10 rare earth elements (REEs) in 171 cases and 171 healthy matched controls were measured by inductively coupled plasma mass spectrometry (ICP-MS). The conditional logistic regression was used to examine the relationship between dietary intake, serum levels of 10 REEs, and tongue cancer. Mediation effect and multiplicative interaction analysis were then performed to estimate the potential contribution of REEs in dietary intake associated with tongue cancer. Results: Compared with the control group, patients with tongue cancer consumed significantly less fish, seafood, fruit, green leafy vegetables, and non-green leafy vegetables, with higher serum praseodymium (Pr), dysprosium (Dy), and lanthanum (La) levels, and lower serum cerium (Ce) and scandium (Sc) levels. The interaction effect was observed between some REEs and food categories. Green vegetables' impact on the risk of tongue cancer is partially attributed to the La and Thorium (Th) elements (P < 0.05, the mediated proportion were 14.933% and 25.280%, respectively). The effect of non-green leafy vegetables for tongue cancer mediated via Pr, Dy, and Th (P < 0.05, the mediated proportion were 0.408%, 12.010%, and 8.969%, respectively), and the Sc components in seafood (P < 0.05, the mediated proportion was 26.120%) is partly responsible for their influence on the risk of tongue cancer. Conclusion: The correlation between REEs and dietary intakes for tongue cancer is compact but intricate. Some REEs interact with food intake to influence tongue cancer, while others act as a mediator.

Ovarian Cancer and Parkinson's Disease: A Bidirectional Mendelian Randomization Study.

(1) Background: Ovarian cancer (OC) and Parkinson's disease (PD) represent a huge public health burden. The relationship of these two diseases is suggested in the literature while not fully understood. To better understand this relationship, we conducted a bidirectional Mendelian ran-domization analysis using genetic markers as a proxy. (2) Methods: Utilizing single nucleotide polymorphisms associated with PD risk, we assessed the association between genetically predicted PD and OC risk, overall and by histotypes, using summary statistics from previously conducted genome-wide association studies of OC within the Ovarian Cancer Association Consortium. Similarly, we assessed the association between genetically predicted OC and PD risk. The inverse variance weighted method was used as the main method to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations of interest. (3) Results: There was no significant association between genetically predicted PD and OC risk: OR = 0.95 (95% CI: 0.88-1.03), or between genetically predicted OC and PD risk: OR = 0.80 (95% CI: 0.61-1.06). On the other hand, when examined by histotypes, a suggestive inverse association was observed between genetically predicted high grade serous OC and PD risk: OR = 0.91 (95% CI: 0.84-0.99). (4) Conclusions: Overall, our study did not observe a strong genetic association between PD and OC, but the observed potential association between high grade serous OC and reduced PD risk warrants further investigation.

Utility of gamma-glutamyl transpeptidase to lymphocyte count ratio in predicting prognosis of patients with oral cancer: A prospective cohort study in Southeastern China.

BACKGROUND: To assess the prognostic role of gamma-glutamyl transpeptidase to lymphocyte count ratio (GLR) and develop a prognostic nomogram for patients with oral cancer. METHODS: A prospective cohort (n = 1011) was conducted during July 2002 to March 2021 in Southeastern China. RESULTS: The median follow-up time was 3.5 years. Multivariate Cox regression (OS: HR = 1.51, 95% CI: 1.04, 2.18) and Fine-Gray model (DSS: HR = 1.68, 95% CI: 1.14, 2.49) both showed that high GLR could act as an indicator of poor prognosis. A nonlinear dose-response relationship was observed between continuous GLR and the risk of all-cause mortality (p for overall = 0.028, p for nonlinear = 0.048). Compare with TNM stage, time-dependent ROC curve proved that GLR-based nomogram model performs better in predicting prognosis (the area under curve for 1-, 3-, and 5-years mortality: 0.63, 0.65, and 0.64 vs. 0.76, 0.77, and 0.78, p < 0.001). CONCLUSION: GLR might be a useful tool in predicting prognosis for patients with oral cancer.

Periodontitis exacerbates atherosclerosis through Fusobacterium nucleatum-promoted hepatic glycolysis and lipogenesis.

AIMS: Positive associations between periodontitis (PD) and atherosclerosis have been established, but the causality and mechanisms are not clear. We aimed to explore the causal roles of PD in atherosclerosis and dissect the underlying mechanisms. METHODS AND RESULTS: A mouse model of PD was established by ligation of molars in combination with application of subgingival plaques collected from PD patients and then combined with atherosclerosis model induced by treating atheroprone mice with a high-cholesterol diet (HCD). PD significantly aggravated atherosclerosis in HCD-fed atheroprone mice, including increased en face plaque areas in whole aortas and lesion size at aortic roots. PD also increased circulating levels of triglycerides and cholesterol, hepatic levels of cholesterol, and hepatic expression of rate-limiting enzymes for lipogenesis. Using 16S ribosomal RNA (rRNA) gene sequencing, Fusobacterium nucleatum was identified as the most enriched PD-associated pathobiont that is present in both the oral cavity and livers. Co-culture experiments demonstrated that F. nucleatum directly stimulated lipid biosynthesis in primary mouse hepatocytes. Moreover, oral inoculation of F. nucleatum markedly elevated plasma levels of triglycerides and cholesterol and promoted atherogenesis in HCD-fed ApoE-/- mice. Results of RNA-seq and Seahorse assay indicated that F. nucleatum activated glycolysis, inhibition of which by 2-deoxyglucose in turn suppressed F. nucleatum-induced lipogenesis in hepatocytes. Finally, interrogation of the molecular mechanisms revealed that F. nucleatum-induced glycolysis and lipogenesis by activating PI3K/Akt/mTOR signalling pathway in hepatocytes. CONCLUSIONS: PD exacerbates atherosclerosis and impairs lipid metabolism in mice, which may be mediated by F. nucleatum-promoted glycolysis and lipogenesis through PI3K/Akt/mTOR signalling in hepatocytes. Treatment of PD and specific targeting of F. nucleatum are promising strategies to improve therapeutic effectiveness of hyperlipidaemia and atherosclerosis.

APOA4 as a novel predictor of prognosis in Stevens-Johnson syndrome/toxic epidermal necrolysis: A proteomics analysis from two prospective cohorts.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening adverse drug reactions. Conventional systemic therapies are of limited efficacy and often exhibit strong side effects. OBJECTIVE: To assess the efficacy and safety of the combination treatment with a tumor necrosis factor-α antagonist adalimumab and delineate the underlying mechanisms. METHODS: We evaluated the efficacy and safety of the combination therapy with adalimumab by comparing 2 treatment cohorts of SJS/TEN patients. Patient plasma samples were collected for proteomics analysis. RESULTS: The combination therapy with adalimumab significantly shortened the time to mucocutaneous re-epithelization and healing, with reduced side effects caused by corticosteroids. Plasma proteomic profiling showed that apolipoprotein A-IV (APOA4) was one of the most significant differentially expressed proteins. Multivariate regression analysis revealed that APOA4 level was significantly associated with prognosis parameter of SJS/TEN (P = .004), but not with disease severity score (severity-of-illness score for toxic epidermal necrolysis [SCORTEN]) (P = .118). Thus further research will be helpful to effectively incorporate APOA4 into current SCORTEN-driven protocols. LIMITATIONS: The cohort size is relatively small. Both cohorts had low overall SCORTEN scores. CONCLUSION: Adalimumab in combination with corticosteroids demonstrates significant clinical benefits over corticosteroids alone in SJS/TEN patients. Moreover, APOA4 may serve as a novel prognostic marker of SJS/TEN.

Invasive Ageratina adenophora can maintain its ecological advantages over time through releasing its autotoxicity by accumulating a bacterium Bacillus cereus.

Plant invasive success is attributed to invaders' ecological advantages over their native neighbors. However, increasing evidence suggests that these advantages are expected to attenuate over time because of natural enemy accumulation, ecological evolution of native species and autotoxicity. We determined how an invasive Ageratina adenophora could remain its competitive advantages over time by avoiding its autotoxicity. Our results highlighted that the autotoxicity of A. adenophora in its invaded soil was reduced by some microbes. Moreover, an autotoxic allelochemical, 2-coumaric acid glucoside, detected in the invaded soil, demonstrated distinctly autotoxic effects on its seed germination and seedling growth. However, the autotoxic effects were greatly alleviated by a bacterium Bacillus cereus, accumulated by A. adenophora. Furthermore, the allelochemical could be almost completely degraded by B. cereus within 96 h. Accordingly, we speculate that A. adenophora could aggregate B. cereus to release its autotoxicity maintaining its competitive advantages over time.

Long non-coding RNA AC018926.2 regulates palmitic acid exposure-compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway.

Although obesity has been proposed as a risk factor for periodontitis, the influence of excessive fat accumulation on the development of periodontitis and periodontal recovery from disease remains largely unknown. This study investigated the cellular response of periodontal ligament stem cells (PDLSCs) to elevated levels of a specific fatty acid, namely, palmitic acid (PA). The mechanism by which PA exposure compromises the osteogenic potential of cells was also explored. It was found that exposure of PDLSCs to abundant PA led to decreased cell osteogenic differentiation. Given that long non-coding RNAs (lncRNAs) play a key role in the stem cell response to adverse environmental stimuli, we screened the lncRNAs that were differentially expressed in PDLSCs following PA exposure using lncRNA microarray analysis, and AC018926.2 was identified as the lncRNA that was most sensitive to PA. Next, gain/loss-of-function studies illustrated that AC018926.2 was an important regulator in PA-mediated osteogenic differentiation of PDLSCs. Mechanistically, AC018926.2 upregulated integrin α2 (ITGA2) expression and therefore activated ITGA2/FAK/AKT signalling. Further functional studies revealed that inactivation of ITGA2/FAK/AKT signalling by silencing ITGA2 counteracted the pro-osteogenic effect induced by AC018926.2 overexpression. Moreover, the results of bioinformatics analysis and RNA immunoprecipitation assay suggested that AC018926.2 might transcriptionally regulate ITGA2 expression by binding to PARP1 protein. Our data suggest that AC018926.2 may serve as a therapeutic target for the management of periodontitis in obese patients.

Exosomal hsa_circRNA_047733 integrated with clinical features for preoperative prediction of lymph node metastasis risk in oral squamous cell carcinoma.

BACKGROUND: To evaluate whether exosomal circRNAs could serve as diagnostic biomarkers for the accurate preoperative prediction of lymph node metastasis (LNM) risk in oral squamous cell carcinoma (OSCC) patients. METHODS: A combinative strategy of exosomal circRNAs microarray and qRT-PCR verification was employed to dig LNM-related circRNA signatures. Then, a dynamic nomogram was developed based on candidate circRNAs and preoperative clinical features and the calibration, discrimination, and clinical use of the nomogram were evaluated. RESULTS: According to the microarray, three circRNAs derived from the tumor were associated with preoperative LNM risk, including hsa_circRNA_047733, hsa_circRNA_024144 and hsa_circRNA_403472. The hsa_circRNA_047733 was further verified to be significantly downregulated in patients with LNM (+) as compared with those with LNM (-) (p = 0.007). Patients with the higher expression of hsa_circRNA_047733 showed a lower risk of LNM (multivariate-adjusted OR = 0.22, 95%CI: 0.06-0.83). The bioinformatics prediction showed that hsa_circRNA_047733 might sponge miR-4464/miR-4748 to regulate RPS21 expression. A dynamic nomogram integrating exosomal hsa_circRNA_047733 with five clinicopathological characteristics (tumor site, leukocyte level, maximum tumor diameter, and LNM reported by MRI and preoperative biopsy differentiation) was developed. The model displayed an excellent discrimination ability (AUC = 0.868, 95%CI: 0.781-0.955) and great calibration. The decision curve revealed a higher net benefit superior to the baseline model at an 80% threshold probability. CONCLUSION: The data provide preliminary evidence that exosomal hsa_circRNA_047733 might be a novel biomarker for the LNM of OSCC. The hsa_circRNA_047733-based dynamic nomogram could serve as a convenient preoperative assessment tool to predict the risk of LNM for OSCC patients.

Effect of transoral laser microsurgery vs open partial laryngectomy on the prognosis of patients with early laryngeal carcinoma: propensity score-based analysis.

OBJECTIVE: To evaluate the effect of surgical procedures (transoral laser microsurgery (TLM) and open partial laryngectomy (OPL)) on the prognosis of patients with early laryngeal cancer. METHODS: A total of 760 patients diagnosed with early laryngeal cancer (T1-2N0M0) and treated with TLM (n = 416) or OPL (n = 344) between 2004 and 2015 were abstracted from the SEER database. Propensity score matching (PSM) and stabilized inverse probability of treatment weighting (SIPTW) were performed to obtain comparable cohorts. The survival rates were estimated by the Kaplan-Meier method, and compared using the log-rank test. Univariate and multivariate Cox regression analyses with a false discovery rate (FDR) correction were applied to contrast the association between two surgical approaches and overall survival (OS) and disease-specific survival (DSS). RESULTS: The 5-year OS for the TLM group was 79.5% versus 77.7% for the OPL group (P = 0.619). Similar results were revealed for the comparison of 5-year DSS rates (91.1% versus 91.5%, P = 0.891). After PSM and SIPTW balance the confounding factors, no significant difference was observed in the OS and DSS of patients treated with TLM compared to patients treated with OPL. The consistent results were still yielded (all P > 0.05), when stratified by gender, age, year of diagnosis, residence, household income, tumor site, T stage, differentiation, and adjuvant therapy. CONCLUSION: This study provides strong evidence that there is no significant difference in the prognosis of early laryngeal carcinoma between the treatment of TLM and OPL, which may be helpful to guide the clinical decision-making of these patients.