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.

Construction and validation of a TAMRGs prognostic signature for gliomas by integrated analysis of scRNA and bulk RNA sequencing data.

BACKGROUND: This study aimed to construct and validate a prognostic model based on tumor associated macrophage-related genes (TAMRGs) by integrating single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data. METHODS: The scRNA-seq data of three inhouse glioma tissues were used to identify the tumor-associated macrophages (TAMs) marker genes, the DEGs from the The Cancer Genome Atlas (TCGA) - Genotype-Tissue Expression (GTEx) dataset were used to further select TAMs marker genes. Subsequently, a TAMRG-score was constructed by Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis in the TCGA dataset and validated in the Chinese Glioma Genome Atlas (CGGA) dataset. RESULTS: We identified 186 TAMs marker genes, and a total of 6 optimal prognostic genes including CKS2, LITAF, CTSB, TWISTNB, PPIF and G0S2 were selected to construct a TAMRG-score. The high TAMRG-score was significantly associated with worse prognosis (log-rank test, P<0.001). Moreover, the TAMRG-score outperformed the other three models with AUC of 0.808. Immune cell infiltration, TME scores, immune checkpoints, TMB and drug susceptibility were significantly different between TAMRG-score groups. In addition, a nomogram were constructed by combing the TAMRG-score and clinical information (Age, Grade, IDH mutation and 1p19q codeletion) to predict the survival of glioma patients with AUC of 0.909 for 1-year survival. CONCLUSION: The high TAMRG-score group was associated with a poor prognosis. A nomogram by incorporating TMARG-score could precisely predict glioma survival, and provide evidence for personalized treatment of glioma.

Association between brominated flame retardants (BFRs) and periodontitis: Results from a large population-based study.

BACKGROUND: Brominated flame retardants (BFRs) are widely utilized to mitigate the flammability of various materials. Previous studies have revealed the impact of BFRs exposure on hormonal disruption and bone metabolism which are closely related to periodontitis. However, it remains unknown the potential relationship between BFRs and periodontitis. This study aimed to explore the association between BFRs exposure and periodontitis in US adults. METHODS: The data analyzed in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009-2014. Twelve serum BFRs were quantified using isotope dilution gas chromatography high-resolution mass spectrometry. Univariable and multivariable logistic regression was employed to evaluate the association between serum BFRs and periodontitis. Bayesian kernel machine regression (BKMR) analyses were utilized to assess the association between mixtures of BFRs and periodontitis. RESULTS: A total of 3311 eligible participants were included. Serum BFRs (PBDE-47, PBDE-99, and PBDE-154) were significantly associated with periodontitis, and the odds ratios (ORs) and corresponding 95% confidence intervals(CIs) were 1.15(1.01,1.29), 1.10(1.01,1.20), and 1.12(1.01,1.25), respectively. Notably, these three BFRs were also significantly associated with the severity of periodontitis. Additionally, the BKMR model revealed a significant association between the mixture of all twelve BFRs and periodontitis. CONCLUSIONS: This preliminary study suggests a significant association between specific serum BFRs (PBDE-47, PBDE-99, and PBDE-154) and periodontitis and its severity. Further prospective and experimental studies are warranted to validate our findings.

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.

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.

Associations of Urinary Total Arsenic and Arsenic Species and Periodontitis.

AIMS: Arsenic exposure is a significant global public health concern and has been implicated in endocrine disruption and increased oxidative stress, both of which are crucial pathogenic mechanisms of periodontitis. This study aimed to investigate the association of urinary total arsenic and arsenic species with periodontitis and to further explore the potential mediating roles of sex hormones and oxidative stress indicators. METHODS: Data used in this study were derived from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) in the US population. In all, 1063 participants with complete data were included in this study. Weighted logistic regression analyses were used to evaluate the relationship between urinary arsenic and periodontitis. Mediation analyses were used to explore the effects of potential mediators on these associations. RESULTS: High concentrations of urinary dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), 2 types of toxic urinary arsenic (TUA2), and 4 types of toxic urinary arsenic (TUA4) were positively related to periodontitis (P < .05). After adjusting for potential confounders, the positive association remained significant (odds ratio, 1.32; 95% confidence interval, 1.01-1.71). Testosterone may partially mediate the relationship between MMA and periodontitis, with mediating effects of 21.78% and 39.73% of the total effect. No significant mediation effect of oxidative stress indicators was found for this relationship. CONCLUSIONS: This study reports a positive association between urinary MMA and periodontitis, and testosterone may mediate this relationship. Our findings serve as a call for action to avoid the deployment of arsenic-containing therapeutic agents as treatment modalities for oral afflictions.

Association of per- and polyfluoroalkyl substances (PFAS) with periodontitis: the mediating role of sex hormones.

OBJECTIVES: To investigate the association between serum per- and polyfluoroalkyl substances (PFAS) and periodontitis, and further explore the possible mediating role of sex hormones in this association. METHODS: We extracted data from National Health and Nutrition Examination Survey (NHANES) 2009-2014. Univariable and multivariable logistic regression models were performed to investigate the association between serum levels of seven PFASs and periodontitis. Bayesian kernel machine regression (BKMR) was conducted to assess the joint effect of PFASs in mixtures. Mediation analyses were used to explore the potential mediating role of sex hormones. RESULTS: Participants with periodontitis had higher concentrations of serum perfluorooctane sulfonate (PFOS) and perfluorononanoic acid (PFNA) than those without periodontitis (both P < 0.05). In fully adjusted models, high serum concentrations of PFOS and PFNA were positively associated with periodontitis (tertile 3 vs. tertile 1: prevalence ratio (PR) = 1.19 for PFOS, 95% CI: 1.01-1.39; PR = 1.17 for PFNA, 95% CI: 1.02-1.34). The results from the BKMR models consistently showed a positive association between PFAS mixtures and periodontitis. Of note, testosterone and the ratio of testosterone to estradiol significantly mediated the relationship between high level of PFOS and periodontitis, accounting for 16.5% and 31.7% of the total effect, respectively. Sensitivity analyses yielded similar results when using periodontal clinical indices (mean loss of attachment, mean periodontal probing depth, and the number of teeth) as dependent variables. CONCLUSIONS: These findings provide evidence to support a positive association between certain PFASs and periodontitis, which might be partially mediated by sex hormones.

Characterization of the m6A/m1A/m5C/m7G-related regulators on the prognosis and immune microenvironment of glioma by integrated analysis of scRNA-seq and bulk RNA-seq data.

BACKGROUND: Proliferation, metabolism, tumor occurrence and development in gliomas are greatly influenced by RNA modifications. However, no research has integrated the four RNA methylation regulators of m6A, m1A, m5C and m7G in gliomas to analyze their relationship with glioma prognosis and intratumoral heterogeneity. METHODS: Based on three in-house single-cell RNA-sequencing (scRNA-seq) data, the glioma heterogeneity and characteristics of m6A/m1A/m5C/m7G-related regulators were elucidated. Based on publicly available bulk RNA-sequencing (RNA-seq) data, a risk-score system for predicting the overall survival (OS) for gliomas was established by three machine learning methods and multivariate Cox regression analysis, and validated in an independent cohort. RESULTS: Seven cell types were identified in gliomas by three scRNA-seq data, and 22 m6A/m1A/m5C/m7G-related regulators among the marker genes of different cell subtypes were discovered. Three m6A/m1A/m5C/m7G-related regulators were selected to construct prognostic risk-score model, including EIFA, NSUN6 and TET1. The high-risk patients showed higher immune checkpoint expression, higher tumor microenvironment scores, as well as higher tumor mutation burden and poorer prognosis compared with low-risk patients. Additionally, the area under the curve values of the risk score and nomogram were 0.833 and 0.922 for 3 year survival and 0.759 and 0.885 for 5 year survival for gliomas. EIF3A was significantly highly expressed in glioma tissues in our in-house RNA-sequencing data (p < 0.05). CONCLUSION: These findings may contribute to further understanding of the role of m6A/m1A/m5C/m7G-related regulators in gliomas, and provide novel and reliable biomarkers for gliomas prognosis and treatment.

Association between Mediterranean diet and periodontitis among US adults: The mediating roles of obesity indicators.

OBJECTIVE: This study aimed to assess the association between the Mediterranean diet (MedDiet) and periodontitis in US adults and to further explore the mediating roles of obesity indicators in this association. BACKGROUND DATA: The relationship between MedDiet and periodontitis is controversial. And it is unclear whether obesity indicators are potential mediators of this relationship. METHODS: Using data derived from the National Health and Nutrition Examination Survey (2009-2014). Weighted binary logistic regression and restricted cubic spline were used to assess the association between MedDiet and periodontitis. Weighted ordinal logistic regression was performed to evaluate the relationship between MedDiet and periodontitis severity. The mediating roles of body mass index (BMI) and waist circumference in the relationship between the MedDiet and periodontitis were explored. Association analyses were further performed using mean clinical attachment loss (CAL) or mean periodontal probing depth (PPD) as dependent variables. The false discovery rate method was used to correct the p-values in the regression analyses. RESULTS: A total of 8290 eligible participants (4159 participants with periodontitis and 4131 without periodontitis) were included. A negative association between the MedDiet adherence score and periodontitis was observed in the binary logistic regression model (adjusted odds ratio = 0.94, 95% confidence interval: 0.90-0.97, p = .001). Restricted cubic spline regression revealed a dose-response relationship between the MedDiet adherence score and periodontitis. BMI and waist circumference significantly mediate this association, with mediation proportions of 9.7% (p = .032) and 9.3% (p = .012), respectively. Multivariable ordinal logistic regression showed that the MedDiet adherence score was negatively associated with the severity of periodontitis (all p < .05). Additionally, the MedDiet adherence score was negatively associated with mean PPD or mean CAL (all p < .05). CONCLUSIONS: This study suggests a significant negative association between adherence to the MedDiet and periodontitis and a possible mediating role of obesity indicators in this association. Furthermore, studies are still warranted to confirm our findings.

Association between polycyclic aromatic hydrocarbons and periodontitis: Results from a large population-based study.

AIM: To explore the association between polycyclic aromatic hydrocarbons (PAHs) (measured using urinary metabolites) and periodontitis using data from the National Health and Nutrition Examination Survey 2009-2014. MATERIALS AND METHODS: Weighted binary logistic regression, Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression were used to evaluate independent and joint associations between the six urinary monohydroxylated metabolites of PAHs (OH-PAHs) and periodontitis. RESULTS: In all, 3413 participants were included in this study. All six urinary OH-PAHs were present at higher levels in the periodontitis group compared with the non-periodontitis group (p < .001). Fully adjusted multivariable logistic regressions showed positive associations between the six urinary OH-PAHs and periodontitis (p < .05). Higher concentrations of OH-PAHs were also positively associated with attachment loss, periodontal pocket depth (PPD) and the number of tooth loss. BKMR and WQS regression yielded similar positive associations between OH-PAH mixtures and periodontitis. CONCLUSIONS: PAHs and their mixture are positively associated with periodontitis, which may provide novel insights into periodontitis prevention from an environmental exposure perspective.

The associations of coffee consumption, coffee types, and caffeine metabolites with periodontitis: Results from NHANES 2009-2014.

BACKGROUND: Coffee is one of the world's most popular beverages and is the main dietary source of caffeine for most people. The various molecular effects of caffeine suggest that it may enhance bone loss. The purpose of the present study was to investigate the relationship of coffee, coffee types, and caffeine metabolites with periodontitis. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009-2014. Total coffee and different types of coffee consumption were acquired through a 24-h dietary recall. Urinary caffeine metabolites were quantified using high-performance liquid chromatography-electrospray ionization-tandem quadrupole mass spectrometry (HPLC-ESI-MS/MS). The association of coffee, coffee types, and caffeine metabolites with periodontitis and its severity were assessed using multivariable logistic regression. RESULTS: A total of 3309 eligible participants were included. After adjusting for potential confounding variables, a positive association was observed between coffee consumption (particularly certain types of coffee) and periodontitis. Notably, a positive correlation was also found between total coffee intake and the severity of periodontitis. Additionally, for urinary caffeine metabolites, there was a significant positive association between 1-methyluric acid (1-MU), 1,3-dimethyluric acid (1,3-DMU), 3,7-dimethyluric acid (3,7-DMU), 1,7-dimethylxanthine (1,7-DMX), or 5-actlyamino-6-amino-3-methyluracil (AAMU) and periodontitis, with adjusted odds ratios and 95% confidence intervals of 1.10 (1.02, 1.19), 1.86 (1.05, 3.29), 0.94 (0.90, 0.98), 1.29 (1.03, 1.62), and 1.15 (1.05, 1.26), respectively. CONCLUSIONS: The present study suggests a positive association of coffee intake (especially certain coffee types) and caffeine metabolites (1-MU, 1,3-DMU, 3,7-DMU, 1,7-DMX, and AAMU) with periodontitis and its severity.

Association of remnant cholesterol with hypertension, type 2 diabetes, and their coexistence: the mediating role of inflammation-related indicators.

PURPOSE: Cholesterol metabolism is a risk factor for cardiovascular disease, and recent studies have shown that cholesterol metabolism poses a residual risk of cardiovascular disease even when conventional lipid risk factors are in the optimal range. The association between remnant cholesterol (RC) and cardiovascular disease has been demonstrated; however, its association with hypertension, type 2 diabetes mellitus (T2DM), and the concomitance of the two diseases requires further study. This study aimed to evaluate the association of RC with hypertension, T2DM, and both in a large sample of the U.S. population, and to further explore the potential mechanisms involved. METHODS: This cross-sectional study used data from the 2005-2018 cycles of the National Health and Nutrition Examination Survey (N = 17,749). Univariable and multivariable logistic regression analyses were performed to explore the relationships of RC with hypertension, T2DM, and both comorbidities. A restricted cubic spline regression model was used to reveal the dose effect. Mediation analyses were performed to explore the potential mediating roles of inflammation-related indicators in these associations. RESULTS: Of the 17,749 participants included (mean [SD] age: 41.57 [0.23] years; women: 8983 (50.6%), men: 8766 (49.4%)), the prevalence of hypertension, T2DM, and their co-occurrence was 32.6%, 16.1%, and 11.0%, respectively. Higher RC concentrations were associated with an increased risk of hypertension, T2DM, and their co-occurrence (adjusted odds ratios for per unit increase in RC were 1.068, 2.259, and 2.362, and 95% confidence intervals were 1.063-1.073, 1.797-2.838, and 1.834-3.041, respectively), with a linear dose-response relationship. Even when conventional lipids were present at normal levels, positive associations were observed. Inflammation-related indicators (leukocytes, lymphocytes, monocytes, and neutrophils) partially mediated these associations. Among these, leukocytes had the greatest mediating effect (10.8%, 14.5%, and 14.0%, respectively). CONCLUSION: The results of this study provide evidence that RC is associated with the risk of hypertension, T2DM, and their co-occurrence, possibly mediated by an inflammatory response.

Effect of heat-clearing and dampness-eliminating Chinese medicine for high-risk cervical cancer papillomavirus infection: a systematic review and meta-analysis of randomized controlled trials.

Background: Heat-clearing and dampness-eliminating Chinese medicine (HDCM) has been studied in clinical trials for cervical HPV infection for decades. However, there has been little comprehensive assessment of the strength and quality of the evidence. Therefore, this study conducted a systematic review and meta-analysis to assess the effectiveness and safety of HDCM in high-risk cervical HPV-infected patients. Methods: The research focus questions were constructed in accordance with the criteria of participants, intervention, comparison, and outcomes (PICO), and a protocol was registered in PROSPERO. Comprehensive and systematic searches and inquiries in eight electronic databases were conducted from their inception to 30th June 2022. Further, a systematic review and meta-analysis of all randomized controlled trials (RCTs) were conducted to evaluate the HDCM therapy methods. Results: A total of 12 studies were eligible for inclusion, including 1,574 patients. Data synthesis showed that the HPV clearance rate of HDCM groups was superior to both interferon and follow-up groups (RR = 1.40,95% CI:1.15, 1.71, P < 0.01) and (RR = 3.15, 95% CI:2.43,4.08, P < 0.01), respectively. HDCM was proven to exhibit greater potential in reducing HPV-DNA virus load (MD = -5.16, 95% CI: -5.91, -4.41, P < 0.01). The reversal rate of cervical intraepithelial neoplasia (CIN) for HDCM groups was approximately 2.8 times (RR = 2.80, 95% CI: 2.19, 3.57, P < 0.01), as high as the follow-up groups. Additionally, the recurrence rate of HR-HPV at the end of follow-up in this meta-analysis was reported to be lower in HDCM groups compared to follow-up groups [6.81% (16/235) and 14.65% (29/198), respectively]. The most commonly used Chinese herbal remedies were as follows: Huangbai (Phellodendron chinense var.Glabriusculum C.K. Schneid.), Kushen (Sophora flavescens Aiton), Daqingye (Isatis indigotica Fortune), Zicao (Arnebia hi-spidissima DC.), Baihuasheshecao (Hedyotis diffusa Spreng.), Banlangen (Isatis tinctoria subsp.tinctoria L.), Huzhang (Reynoutria japonica Houtt.), and Huangqi (Orobanche astragali Mouterde). Conclusion: HDCM interventions appeared to generate significant effects on enhancing the rate of HR-HPV clearance, reducing the HPV-DNA virus load, and increasing the CIN regression rate. Some active components were confirmed to be responsible for this efficacy, which deserves further exploration. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022333226.

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.

Scientific creativity and innovation ability and its determinants among medical postgraduate students in Fujian province of China: a cross sectional study.

BACKGROUND: Graduate education is the main approach to training high-level innovative elites. With the expansion of the scale of graduate education in China, it has gradually emerged that the lack of innovation ability of graduate students is recognized as the primary problem in graduate education. How to comprehensively improve the quality of postgraduate teaching has become the core task of educational reform and development. However, data about the current cultivation and development of the innovative ability of graduate students in China is limited. METHODS: A questionnaire survey was conducted among medical postgraduate students. Descriptive statistics and multiple regression analysis methods were used to analyze the data to describe the current innovation ability in advanced medical education and potential influence factors. RESULTS: A total of 1241 medical students were surveyed, according to the results of questionnaire data analysis. The proportion of subjects who participated in the College Student's Entrepreneurship and Innovation program or any other scientific research programs are fairly high which are 46.82% and 29.20% respectively. Most of the participants are observed with high levels of self-motivation and active learning and have good performance in creative thinking. However, only a small number of participants (16.6%) reported academic achievements such as publications. Most of the students are satisfied with the current scientific research environment and think that the current postgraduate training system is qualified for the cultivation of innovation ability, and expects the inclusion of course specialized in systemic medicine and medical informatics in the curricula. Multiple logistic regression results showed that among the factors studied, gender, medical specialties, and types of master's degrees are associated with cognition & skills, academic performance, and creativity. CONCLUSIONS: It will be important to incorporate more techniques for creating and improving creativity in the curricula of the current postgraduate education, especially for courses such as systemic medicine and informatics. Guidance in earlier school life can stimulate creativity and an early introduction to scientific research work will facilitate innovative thinking and behavior. Scientific research programs such as the National Innovation and Entrepreneurship Training for the universities of PRC have been widely implemented in the undergraduate education system throughout the country. However, the training effectiveness of the current scientific research programs is worth improving.

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.

C-reactive protein and lactate dehydrogenase serum levels potentially predict the response to checkpoint inhibitors in patients with advanced non-small cell lung cancer.

Background: Programmed cell death-ligand 1 (PD-L1) expression and other biomarkers are not completely reliable predictors of the response to checkpoint inhibitors in patients with advanced non-small cell lung cancer (NSCLC). We investigated the value of peripheral serological inflammatory indicators and their combination in predicting the prognosis of patients with advanced NSCLC treated with checkpoint inhibitors. Methods: This study retrospectively analyzed 116 NSCLC patients treated with anti-programmed cell death protein 1 (PD-1)/PD-L1 monoclonal antibodies. Clinical data of the patients were collected before treatment. X-tile plots determined the optimal cut-point for C-reactive protein (CRP) and lactate dehydrogenase (LDH). A survival analysis was performed using the Kaplan-Meier method. Multi-factor Cox regression analysis was used to evaluate the statistically significant factors identified in the univariate analysis. Results: The X-tile plots show the cut-points of CRP and LDH were 8 mg/L and 312 U/L, respectively. Univariate analyses showed high baseline serum LDH and low CRP levels were associated with adverse progression-free survival (PFS). Multivariate analyses indicated that CRP (HR, 0.214, 95% CI: 0.053-0.857, P=0.029) could be a predictive indicator for PFS. In addition, we evaluated the combination of CRP and LDH, and univariate analyses showed that patients with high CRP and low LDH exhibited significantly better PFS than those in the other groups. Conclusions: Baseline levels of serum CRP and LDH have the potential to become a convenient clinical tool to predict response to immunotherapy in advanced non-small cell lung cancer.

Single-cell RNA-Seq and bulk RNA-Seq reveal reliable diagnostic and prognostic biomarkers for CRC.

PURPOSE: The potential role of epithelium-specific genes through the adenoma-carcinoma sequence in the development of colorectal cancer (CRC) remains unknown. Therefore, we integrated single-cell RNA sequencing and bulk RNA sequencing data to select diagnosis and prognosis biomarkers for CRC. METHODS: The CRC scRNA-seq dataset was used to describe the cellular landscape of normal intestinal mucosa, adenoma and CRC and to further select epithelium-specific clusters. Differentially expressed genes (DEGs) of epithelium-specific clusters were identified between intestinal lesion and normal mucosa in the scRNA-seq data throughout the adenoma-carcinoma sequence. Diagnostic biomarkers and prognostic biomarker (the risk score) for CRC were selected in the bulk RNA-seq dataset based on DEGs shared by the adenoma epithelium-specific cluster and the CRC epithelium-specific cluster (shared-DEGs). RESULTS: Among the 1063 shared-DEGs, we selected 38 gene expression biomarkers and 3 methylation biomarkers that had promising diagnostic power in plasma. Multivariate Cox regression identified  174 shared-DEGs as prognostic genes for CRC. We combined 1000 times LASSO-Cox regression and two-way stepwise regression to select 10 prognostic shared-DEGs to construct the risk score in the CRC meta-dataset. In the external validation dataset, the 1- and 5-year AUCs of the risk score were higher than those of stage, the pyroptosis-related genes (PRG) score and the cuproptosis-related genes (CRG) score. In addition, the risk score was closely associated with the immune infiltration of CRC. CONCLUSION: The combined analysis of the scRNA-seq dataset and the bulk RNA-seq dataset in this study provides reliable biomarkers for the diagnosis and prognosis of CRC.