Association of healthy diet score and adiposity with risk of colorectal cancer: findings from the UK Biobank prospective cohort study.

PURPOSE: To explore the joint association of dietary patterns and adiposity with colorectal cancer (CRC), and whether adiposity mediates the relationship between dietary patterns and CRC risk, which could provide deeper insights into the underlying pathogenesis of CRC. METHODS: The data of 307,023 participants recruited between 2006 and 2010 were extracted from the UK Biobank study. Healthy diet scores were calculated based on self-reported dietary data at baseline, and participants were categorized into three groups, namely, low, intermediate, and high diet score groups. Cox regression models with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the effects of the healthy diet score on CRC incidence, adjusting for various covariates. Furthermore, the mediation roles of obesity and central obesity between the healthy diet score and CRC risk were assessed using a counterfactual causal analysis based on Cox regression model. Additionally, joint association between dietary patterns and adiposity on CRC risks was assessed on the additive and multiplicative scales. RESULTS: Over a median 6.2-year follow-up, 3,276 participants developed CRC. After adjusting for sociodemographic and lifestyle factors, a lower risk of CRC incidence was found for participants with intermediate (HR = 0.83, 95% CI: 0.72 to 0.95) and high diet scores (HR = 0.73, 95% CI: 0.62 to 0.87) compared to those with low diet scores. When compared with the low diet score group, obesity accounted for 4.13% and 7.93% of the total CRC effect in the intermediate and high diet score groups, respectively, while central obesity contributed to 3.68% and 10.02% of the total CRC risk in the intermediate and high diet score groups, respectively. The mediating effect of adiposity on CRC risk was significant in men but not in women. Concurrent unhealthy diet and adiposity multiplied CRC risk. CONCLUSION: Adiposity-mediated effects were limited in the link between dietary patterns and CRC incidence, implying that solely addressing adiposity may not sufficiently reduce CRC risk. Interventions, such as improving dietary quality in people with adiposity or promoting weight control in those with unhealthy eating habits, may provide an effective strategy to reduce CRC risk.

Effects of 24-hour urine-output trajectories on the risk of acute kidney injury in critically ill patients with cirrhosis: a retrospective cohort analysis.

BACKGROUND: Acute kidney injury (AKI) is one of the most common complications for critically ill patients with cirrhosis, but it has remained unclear whether urine output fluctuations are associated with the risk of AKI in such patients. Thus, we explored the influence of 24-h urine-output trajectory on AKI in patients with cirrhosis through latent category trajectory modeling. MATERIALS AND METHODS: This retrospective cohort study examined patients with cirrhosis using the MIMIC-IV database. Changes in the trajectories of urine output within 24 h after admission to the intensive care unit (ICU) were categorized using latent category trajectory modeling. The outcome examined was the occurrence of AKI during ICU hospitalization. The risk of AKI in patients with different trajectory classes was explored using the cumulative incidence function (CIF) and the Fine-Gray model with the sub-distribution hazard ratio (SHR) and the 95% confidence interval (CI) as size effects. RESULTS: The study included 3,562 critically ill patients with cirrhosis, of which 2,467 (69.26%) developed AKI during ICU hospitalization. The 24-h urine-output trajectories were split into five classes (Classes 1-5). The CIF curves demonstrated that patients with continuously low urine output (Class 2), a rapid decline in urine output after initially high levels (Class 3), and urine output that decreased slowly and then stabilized at a lower level (Class 4) were at higher risk for AKI than those with consistently moderate urine output (Class 1). After fully adjusting for various confounders, Classes 2, 3, and 4 were associated with a higher risk of AKI compared with Class 1, and the respective SHRs (95% CIs) were 2.56 (1.87-3.51), 1.86 (1.34-2.59), and 1.83 1.29-2.59). CONCLUSIONS: The 24-h urine-output trajectory is significantly associated with the risk of AKI in critically ill patients with cirrhosis. More attention should be paid to the dynamic nature of urine-output changes over time, which may help guide early intervention and improve patients' prognoses.

Accuracy and clinical characteristics of robot-assisted cervical spine surgery: a systematic review and meta-analysis.

PURPOSE: To evaluate the accuracy and feasibility of robot-assisted cervical screw placement and factors that may affect the accuracy. METHODS: A comprehensive search was made on PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang Med for the selection of potential eligible literature. The outcomes were evaluated in terms of the relative risk (RR) or standardized mean difference (MD) and corresponding 95% confidence interval (CI). Subgroup analyses of the accuracy of screw placement at different cervical segments and with different screw placement approaches were performed. A comparison was made between robotic navigation and conventional freehand cervical screw placement. RESULTS: Six comparative cohort studies and five case series studies with 337 patients and 1342 cervical screws were included in this study. The perfect accuracy was 86% (95% CI, 82-89%) and the clinically acceptable rate was 98% (95% CI, 95-99%) in robot-assisted cervical screw placement. The perfect accuracy of robot-assisted C1 lateral mass screw placement was the highest (96%), followed by C6-7 pedicle screw placement (93%) and C2 pedicle screw placement (86%), and the lowest was C3-5 pedicle screw placement (75%). The open approach had a higher perfect accuracy than the percutaneous/intermuscular approach (91% vs 83%). Compared with conventional freehand cervical screw placement, robot-assisted cervical screw placement had a higher accuracy, a lower incidence of perioperative complications, and less intraoperative blood loss. CONCLUSION: With good collaboration between the operator and the robot, robot-assisted cervical screw placement is accurate and feasible. Robot-assisted cervical screw placement has a promising prospect.

Secular trend in disease burden of leukemia and its subtypes in China from 1990 to 2019 and its projection in 25 years.

Leukemia and its subtypes impose a major public health challenge in China. Identifying the secular trend of leukemia burden is critical to facilitate optimal healthcare planning and improve the management of leukemia. The incidence rates of leukemia from 1990 to 2019 were collected from the Global Burden of Disease Study 2019 database according to the following: subtype (acute lymphocytic leukemia [ALL], acute myeloid leukemia [AML], chronic lymphocytic leukemia [CLL], chronic myelogenous leukemia [CML], and other leukemia subtypes), sex, and age group. The average annual percentage changes and relative risks were calculated using joinpoint regression and the age-period-cohort model, respectively. The Bayesian age-period-cohort model was also applied to predict the future trend of the incidence of leukemia and its subtypes in the next 25 years. From 1990 to 2019, the age-standardized incidence rates (ASIRs) of leukemia slightly declined in males and females, which is similar to the trend of other leukemia subtypes. However, the four major leukemia subtypes, namely, ALL, AML, CLL, and CML, have been on the rise over the past three decades. The incidence rates of leukemia in children and the elderly were considerably higher than those in other age groups in males and females. Age effects were the most influential risk factor for leukemia incidence. Period effects showed that the risks of leukemia and its subtypes incidence increased with time. For cohort effects, the risks of leukemia and its subtypes were higher among the early-born cohorts compared with the late-born cohorts. The ASIRs of leukemia and its subtypes will continue to increase in the next 25 years. The burden of leukemia and its subtypes is expected to continue to increase in the next 25 years in males and females. A comprehensive understanding of the risk characteristics and disease pattern of leukemia and its subtypes is needed to formulate timely and effective intervention measures to reduce the leukemia burden in China.

Machine learning for the prediction of acute kidney injury in patients with sepsis.

BACKGROUND: Acute kidney injury (AKI) is the most common and serious complication of sepsis, accompanied by high mortality and disease burden. The early prediction of AKI is critical for timely intervention and ultimately improves prognosis. This study aims to establish and validate predictive models based on novel machine learning (ML) algorithms for AKI in critically ill patients with sepsis. METHODS: Data of patients with sepsis were extracted from the Medical Information Mart for Intensive Care III (MIMIC- III) database. Feature selection was performed using a Boruta algorithm. ML algorithms such as logistic regression (LR), k-nearest neighbors (KNN), support vector machine (SVM), decision tree, random forest, Extreme Gradient Boosting (XGBoost), and artificial neural network (ANN) were applied for model construction by utilizing tenfold cross-validation. The performances of these models were assessed in terms of discrimination, calibration, and clinical application. Moreover, the discrimination of ML-based models was compared with those of Sequential Organ Failure Assessment (SOFA) and the customized Simplified Acute Physiology Score (SAPS) II model. RESULTS: A total of 3176 critically ill patients with sepsis were included for analysis, of which 2397 cases (75.5%) developed AKI during hospitalization. A total of 36 variables were selected for model construction. The models of LR, KNN, SVM, decision tree, random forest, ANN, XGBoost, SOFA and SAPS II score were established and obtained area under the receiver operating characteristic curves of 0.7365, 0.6637, 0.7353, 0.7492, 0.7787, 0.7547, 0.821, 0.6457 and 0.7015, respectively. The XGBoost model had the best predictive performance in terms of discrimination, calibration, and clinical application among all models. CONCLUSION: The ML models can be reliable tools for predicting AKI in septic patients. The XGBoost model has the best predictive performance, which can be used to assist clinicians in identifying high-risk patients and implementing early interventions to reduce mortality.

Secular trends in the incidence of eating disorders in China from 1990 to 2017: a joinpoint and age-period-cohort analysis.

BACKGROUND: Eating disorders (ED) have increasingly become a global topic of concern for public health. A better understanding of ED incidence is a basic requirement for improving its management. However, the temporal trend of ED incidence in China is still unknown. METHODS: The incidence rates of ED from 1990 to 2017 were collected from the Global Burden of Disease Study 2017 database according to the following: subtype, i.e. anorexia nervosa (AN) and bulimia nervosa (BN); sex; and age group. The average annual percent changes and relative risks were calculated using joinpoint regression and the age-period-cohort model, respectively. RESULTS: From 1990 to 2017, age-standardized incidence rates of ED continued to increase in males and females, and this variation trend was observed in AN and BN. Joinpoint regression analysis showed that the incidence rates increased in all age groups. Adolescents had the highest risk of developing ED, followed by young adults. Age effects were the most influential risk factor for ED incidence. Period effects showed that the risk of developing ED continuously increased with increasing time periods in BN, but not in ED and AN. Concerning the cohort effects, people born after the 1990s presented a higher risk of ED, though they presented a lower risk of BN as compared to the whole cohort. CONCLUSIONS: ED incidence rates continue to increase in China, particularly among adolescents and young adults. Further etiological studies are needed to explain these increases and to facilitate the early identification of high-risk individuals.

Preoperative C-reactive protein to prealbumin ratio is independently associated with prognosis in patients with resectable colorectal cancer.

BACKGROUND: Increasing attention has been drawn the prognostic value of inflammatory indices for colorectal cancer (CRC). However, the prognostic value of the preoperative C-reactive protein to prealbumin ratio (CPAR) in CRC remains unclear. METHODS: A retrospective study was conducted with 794 patients who had CRC and underwent radical surgical resection. The predictive performance of the inflammatory indices was analyzed and compared using the area under the time-dependent receiver operating characteristic curve. A competing risk regression model and Cox proportional hazard model were used to analyze the effects of CPAR on disease-free survival (DFS) and overall survival (OS), respectively. RESULTS: Patients with high CPAR (>7.25) had poor survival outcome. The CPAR had the best predictive performance among all inflammatory indices, and was significantly associated with several characteristics of tumor invasion, including histological grade, tumor stage, and tumor size. Multivariate analysis showed that high CPAR was independently associated with poor DFS (subdistribution hazard ratio = 2.28, 95% confidence interval [CI]: 1.74-2.82) and OS (hazard ratio = 1.78, 95% CI: 1.60-1.96). CONCLUSION: Preoperative CPAR assessment could serve as an effective and reliable tool for prognostic prediction in patients with resectable CRC.

Health Effects of Tobacco at the Global, Regional, and National Levels: Results From the 2019 Global Burden of Disease Study.

INTRODUCTION: The purpose was to quantify the health effects of tobacco using data from the 2019 Global Burden of Disease study. AIMS AND METHODS: We collected detailed information on tobacco consumption overall as well as its individual aspects (smoking, secondhand smoke, and chewing tobacco) for the deaths and disability-adjusted life years (DALYs) for all-cause disease, cardiovascular disease, neoplasms, and chronic respiratory diseases, and their age-standardized rates (ASRs). RESULTS: Tobacco was responsible for 8.71 million deaths and 229.77 million DALYs globally in 2019. The ASRs of all tobacco-related deaths and DALYs declined from 1990 to 2019, to 108.55 deaths per 100 000 population and 2791.04 DALYs per 100 000 population in 2019. During any year the ASRs of all tobacco-related deaths and DALYs were higher in males than in females. The ASRs of all tobacco-related deaths and DALYs were highest in countries with a low-middle sociodemographic index (SDI) and lowest in high-SDI countries in 2019. Cardiovascular disease, neoplasms, and chronic respiratory diseases were the three leading causes of tobacco-related mortality. CONCLUSIONS: Although the ASRs of deaths and DALYs related to tobacco have declined, the absolute number remain high. Tobacco control policies need to be strengthened further in order to reduce the heavy health burden of tobacco. IMPLICATIONS: This study provides a detailed description on the health effects of tobacco, including maps of the current global burden of tobacco-related disease. Although the ASRs of tobacco-related deaths and DALYs have declined, the absolute numbers remain high-tobacco was responsible for 8.71 million deaths and 229.77 million DALYs globally in 2019. The findings may have implications for tobacco control. Countries where progress has been slower in reducing tobacco-related disease burden should study and consider implementing policies and strategies that have been applied in countries like Singapore which show the greatest declines for recent decades.

Association of Red Cell Distribution Width-to-Platelet Ratio and Mortality in Patients with Sepsis.

Background: As a novel inflammatory index, the ratio of red cell distribution width (RDW) to platelet count (RPR) may have prognostic value in some critical illnesses. However, studies on the prognostic influence of RPR in patients with sepsis are few. This study is aimed at investigating the association between RPR levels and 28-day mortality in patients with sepsis. Methods: Data of patients with sepsis were obtained from the Medical Information Mart for Intensive Care III database. The best cut-off value was calculated by establishing the receiver operating characteristic curve (ROC), and the predictive ability of different indicators was compared through the area under the curve (AUC). The association between RPR levels and 28-day mortality was assessed using the Cox proportional hazards model. Restrictive cubic spline analysis was applied to the multivariable Cox model to investigate the nonlinear relationship between RPR and 28-day mortality. Results: A total of 3367 patients with sepsis were included in the study. A nonlinear relationship was observed between RPR and 28-day mortality, showing a trend of a first rapid increase and a gradual increase. For the prediction of mortality, the best cut-off value for RPR was 0.109, with an AUC of 0.728 (95% confidence interval [CI]: 0.709-0.747). The predictive capability of RPR was superior to those of RDW, platelet, SOFA score, and SAPS II score. After adjusting for various confounding factors, high RPR was significantly associated with increased mortality with adjusted hazard ratios of 1.210 (95% CI: 1.045-1.400) for categorical variables and 2.826 (95% CI: 2.025-3.944) for continuous variables. Conclusion: Elevated RPR level is significantly correlated with a high risk of 28-day mortality in patients with sepsis and can be a new predictor of patient prognosis.

Global, regional and national disability-adjusted life years due to HIV from 1990 to 2019: findings from the Global Burden of Disease Study 2019.

OBJECTIVES: Increasing life expectancy and decreasing mortality in patients with HIV infection are well documented. However, details of how many of the years of healthy life are damaged by HIV infection vs. good health have not been understood. We conducted this study to provide a comprehensive assessment of the levels and trends of the global burden, as measured by disability-adjusted life years (DALYs), of HIV infection. METHODS: Data on HIV-related DALY were obtained from the Global Burden of Disease Study 2019. The absolute numbers and age-standardised rates of DALYs due to HIV were reported between 1990 and 2019. Estimated annual percentage changes in age-standardised rates by sex, region and nation were calculated to quantify the temporal trends in HIV burden. RESULTS: Global HIV infection caused 47.63 million DALYs in 2019, presenting a 1.28-fold increase from 1990 to 2019. In 2019, years of life lost contributed to most of the total DALYs, but the increases in HIV-related years lived with disability have outpaced increases in years of life lost. The age-standardised rates of HIV-related DALYs in 2019 decreased as the sociodemographic indexes increased. The highest age-standardised rates were observed in sub-Saharan Africa, and the greatest increments over time were detected in Oceania. CONCLUSIONS: Globally, HIV continues to cause enormous healthy life loss. The first and foremost strategy for controlling the HIV burden is still the reduction of premature deaths, and much effort needs to be exerted to mitigate the harm of comorbidities.

Simple Method for the Extraction and Determination of Ti-, Zn-, Ag-, and Au-Containing Nanoparticles in Sediments Using Single-Particle Inductively Coupled Plasma Mass Spectrometry.

The quantitative analysis of nanoparticles (NPs) in the environment is significantly important for the exploration of the occurrence, fate, and toxicological behaviors of NPs and their subsequent environmental risks. Some protocols have been recommended for the separation and extraction of NPs that are potentially dispersed in complex environmental matrixes, e.g. sediments and soils, but they remain limited. However, certain factors that may significantly affect extraction efficiency have not been comprehensively explored. In this study, on the basis of the single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS) technique, a simple standardized protocol for separating and analyzing metal-containing NPs in sediment samples was developed. On consideration of the extraction efficiencies of indigenous NPs (Ti- and Zn-NPs) and spiked NPs (Ag- and Au-NPs) in sediments, sedimentation with a settling time of 6 h is recommended for the separation of NPs and large particles, and the optimal sediment to water ratio, ultrasonication power, time, and temperature are 0.4 mg/mL, 285 W, 20 min, and 15-25 °C, respectively. On the basis of the optimized method, the recoveries of spiked Ag and Au-NPs were 71.4% and 81.1%, respectively. The applicability of the optimal protocols was verified, and TOC was proved to be an important factor controlling the separation and extraction of NPs in environmental samples. The separation and extraction of NPs in elevated TOC samples can be improved by increasing the ultrasonication power, time, and temperature.

Metal-Containing Nanoparticles in Low-Rank Coal-Derived Fly Ash from China: Characterization and Implications toward Human Lung Toxicity.

Characterization of nanoparticles (NPs) in coal fly ashes (CFAs) is critical for better understanding the potential health-related risks resulting from coal combustion. Based on single-particle (SP)-inductively coupled plasma mass spectrometry (ICP-MS) coupled with transmission electron microscopy techniques, this study is the first to determine the concentrations and sizes of metal-containing NPs in low-rank coal-derived fly ashes. Despite only comprising a minor component of the studied CFAs by mass, NPs were the dominant fraction by particle number. Fe- and Ti-containing NPs were identified as the dominant NPs with their particle number concentration ranging from 2.5 × 107 to 2.5 × 108 particles/mg. In addition, the differences of Fe-/Ti-containing NPs in various CFAs were regulated by the coalification degree of feed coals and combustion conditions of all of the low-rank CFAs tested. In the cases where these NPs in CFAs become airborne and are inhaled, they can be taken up in pulmonary interstitial fluids. This study shows that in Gamble's solution (a lung fluid simulant), 51-87% of Fe and 63-89% of Ti (ratio of the mass of Fe-/Ti-containing NPs to the total mass of Fe/Ti) exist in the NP form and remain suspended in pulmonary fluid simulants. These NPs are bioavailable and may induce lung tissue damage.

Immunization with oral KISS1 DNA vaccine inhibits testicular Leydig cell proliferation mainly via the hypothalamic-pituitary-testicular axis and apoptosis-related genes in goats.

This study aimed to analyze the effect and mechanism of immunization of oral KISS1 DNA vaccine on the proliferation of goat testicular Leydig cells. Ten 8-week-old male goats were randomly divided into KISS1 DNA vaccine and control groups for immunization (five goats each group). These goats were sacrificed at 8 weeks after primary immunization, and the tissue samples of hypothalamus, pituitary, and testis and Leydig cell samples were collected for RT-PCR and CCK8 assay. Immunization with the oral KISS1 DNA vaccine effectively inhibited the proliferation of Leydig cells, the expression of hypothalamus KISS1, GPR54, and GnRH mRNA, pituitary GnRHR and LH mRNA, testicular LHR mRNA, and apoptosis-inhibitory gene Bcl-2 mRNA in Leydig cells. By contrast, the immunization enhanced the mRNA expression of apoptosis-promoting gene Bax and Clusterin in Leydig cells. These findings indicate that immunization with the oral KISS1 DNA vaccine can inhibit the proliferation of goat testicular Leydig cells mainly via the hypothalamic-pituitary-testicular axis and apoptosis-related genes.

Correction to: Nomogram predicting cancer-specific mortality in early-onset rectal cancer: a competing risk analysis.

The original version of this article, unfortunately, contained errors.

Nomogram predicting cancer-specific mortality in early-onset rectal cancer: a competing risk analysis.

BACKGROUND: The incidence of rectal cancer has meaningfully increased in young patients. However, quantitative evaluation for the competing data of early-onset rectal cancer is lacking. So, we performed a competing risk analysis to calculate the cumulative incidence of death for patients with early-onset rectal cancer and developed a nomogram to predict the probability of cancer-specific mortality for these patients. METHODS: We abstracted data of patients with early-onset rectal cancer between 2004 and 2016 by using the Surveillance, Epidemiology, and End Results program database. The cumulative incidence function was used to calculate the crude cancer-specific mortality of early-onset rectal cancer. Fine and Gray's proportional sub-distribution hazard model was adopted to explore the risk factors of cancer-specific death. Then, we establish a nomogram to predict their 3-, 5-, and 10-year probabilities. RESULTS: We identified 9917 patients with early-onset rectal cancer, and they were randomly divided into training (n = 6941) and validation (n = 2976) cohorts. In the training cohort, the 3-, 5-, and 10-year cumulative incidences of cancer-specific death after diagnosis for early-onset rectal cancer were 11.4%, 19.9%, and 28.8%, respectively. Fine and Gray's model showed that sex, race, marital status, histology, T stage, N stage, M stage, examined lymph nodes, and pretreatment carcinoembryonic antigen were independently associated with cancer-specific mortality. Such factors were selected to develop a prognostic nomogram. CONCLUSION: The competing risk nomogram has an ideal performance for predictive cancer-specific mortality in early-onset rectal cancer.

The Effect of Antioxidant Vitamins on Patients With Diabetes and Albuminuria: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: This study aimed to investigate the effect of antioxidant vitamins, including vitamins E and C, on patients with diabetes and albuminuria by conducting a meta-analysis of randomized controlled trials. DESIGN: The PubMed, Embase, CENTRAL (the Cochrane Central Register of Controlled Trials at the Cochrane Library), Web of Science, OVID, and www.clinicaltrials.gov (latest search: December 10, 2018) databases were searched. This study was limited to randomized controlled trials. Patients with diabetes and albuminuria were included regardless of diabetic type, and patients must have received treatment with vitamins C or E. RESULTS: Ten studies, representing 445 participants, were identified for analysis. Antioxidant vitamins had significant effects on serum creatinine levels (mean difference = -0.11 mg/dL, 95% confidence interval -0.19 to -0.03, P = .007) and systolic pressure (mean difference = -6.02 mm Hg, 95% confidence interval -9.65 to -2.40, P = .001) with low heterogeneity. Antioxidant vitamins had no effect on albuminuria or proteinuria, diastolic blood pressure, glucose, or lipid metabolism. CONCLUSION: This meta-analysis indicated that antioxidant vitamins can benefit kidney function and systolic blood pressure in patients with diabetes and albuminuria. Further studies with larger sample sizes and longer follow-up are needed to completely understand the effect of antioxidant vitamins in these patients.

Accuracy of Fukuoka and American Gastroenterological Association Guidelines for Predicting Advanced Neoplasia in Pancreatic Cyst Neoplasm: A Meta-Analysis.

BACKGROUND: A differential diagnosis of advanced pancreatic cystic neoplasms (PCNs) is critical to determine optimal treatment. The Fukuoka and American Gastroenterological Association (AGA) guidelines are the most widely accepted criteria for the management of PCNs. OBJECTIVE: This study aimed to evaluate the diagnostic value of these guidelines in predicting advanced neoplasia (AN). METHODS: A comprehensive electronic search of the PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases was conducted to identify all relevant studies evaluating the Fukuoka and AGA guidelines in surgically resected and histologically confirmed PCNs. Pooled sensitivity, specificity, and diagnostic odds ratios (DORs) were calculated as compound measures of diagnostic accuracy using the random-effects model. Summary of receiver operating characteristic (SROC) curves and the area under the curve (AUC) were also performed. RESULTS: A total of 21 studies with 3723 patients were included in this meta-analysis. Of these studies, 15, 4, and 2 evaluated the Fukuoka guidelines, the AGA guidelines, and both guidelines, respectively. For AN prediction, the Fukuoka guidelines had a pooled sensitivity of 0.67 (95% confidence interval [CI] 0.64-0.70), pooled specificity of 0.64 (95% CI 0.62-0.66), and pooled DOR of 6.28 (95% CI 4.38-9.01), with an AUC of the SROC of 0.78. AGA guidelines showed a pooled sensitivity of 0.59 (95% CI 0.52-0.65), pooled specificity of 0.77 (95% CI 0.74-0.80), and pooled DOR of 5.84 (95% CI 2.60-13.15), with an AUC of 0.79 (95% CI 0.70-0.88). CONCLUSION: When used alone, the Fukuoka and AGA guidelines showed similar but unsatisfactory diagnostic accuracy in the risk stratification of malignant potential of PCN. Thus, we recommend that they be applied only as a broad framework in clinical practice.

Construction of a fusion anti-caries DNA vaccine in transgenic tomato plants for PAcA gene and cholera toxin B subunit.

Chronic bacterial infections in the oral cavity influence the development of dental caries. Mutans streptococci are the major pathogenic cause of dental caries. The World Health Organization (WHO) ranks dental caries, cancer, and cardiovascular diseases as the three major global diseases that need urgent preventative and curative measures. However, substantial evidence suggests that traditional prevention and treatment strategies are inefficient in reducing the prevalence of dental caries. For protection against caries, it is important to develop effective vaccines that induce anticolonizing immunity against Streptococcus mutans infections. In the present investigation, we constructed a fusion anti-caries DNA vaccine (PAcA-ctxB) through fusing A region of cell surface protein PAc (PAcA) coding gene of mutans streptococci with cholera toxin B subunit coding gene (CTB). Afterward, the plasmids were integrated into tomato genomes through agrobacterium-mediated plant transformation technology. The presence of transgenes in the tomato genome was confirmed by PCR, ß-glucuronidase gene (GUS), and western blot. The expression of genes was confirmed at transcription and protein level. Altogether, the results presented herein showed that transgenic tomatoes may provide a useful system for the production of human caries antigen.

Expression of PD1 and BTLA on the CD8+ T Cell and γδT Cell Subsets in Peripheral Blood of Non-Small Cell Lung Cancer Patients.

Objective To investigate the expression and regulation of programmed cell death protein 1 (PD1), B lymphocyte and T lymphocyte attenuator (BTLA) in peripheral blood of patients with non-small cell lung cancer (NSCLC); to examine the correlation of the mRNA levels between PD and BTLA in NSCLC. Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8+ T cells and γδ+ T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals. We compared the expression of PD1 and BTLA on the surfaces of γδ+ T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid. The correlations of PD1 and BTLA, as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform. Results The frequency of PD1 on the surfaces of CD8+ T cells was significantly higher than that of the γδT cells in both healthy controls (t=2.324, P=0.024) and NSCLC patients（t=2.498, P=0.015). The frequency of PD1 on CD8+ T cells, rather than on γδ+ T cells, was significantly upregulated in advanced NSCLC patients compared with that in healthy controls (t=4.829, P<0.001). The PD1+ BTLA+γδT cells of the healthy controls were significantly lower than that of the NSCLC patients (t=2.422, P=0.0185). No differences in percentage of PD1+γδ+ and BTLA+γδ+ T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment. PD1 was positively correlated with BTLA in both lung adenocarcinoma (r=0.54; P<0.05) and lung squamous cell carcinoma (r=0.78; P<0.05). Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8+ T cells and γδT cells in advanced NSCLC, suggesting that these molecules were involved in regulating the inactivation of CD8+ T cells and γδ+ T cells, immune escape and tumor invasion.