Prediction of esophageal cancer risk based on genetic variants and environmental risk factors in Chinese population.

BACKGROUND: Results regarding whether it is essential to incorporate genetic variants into risk prediction models for esophageal cancer (EC) are inconsistent due to the different genetic backgrounds of the populations studied. We aimed to identify single-nucleotide polymorphisms (SNPs) associated with EC among the Chinese population and to evaluate the performance of genetic and non-genetic factors in a risk model for developing EC. METHODS: A meta-analysis was performed to systematically identify potential SNPs, which were further verified by a case-control study. Three risk models were developed: a genetic model with weighted genetic risk score (wGRS) based on promising SNPs, a non-genetic model with environmental risk factors, and a combined model including both genetic and non-genetic factors. The discrimination ability of the models was compared using the area under the receiver operating characteristic curve (AUC) and the net reclassification index (NRI). The Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to assess the goodness-of-fit of the models. RESULTS: Five promising SNPs were ultimately utilized to calculate the wGRS. Individuals in the highest quartile of the wGRS had a 4.93-fold (95% confidence interval [CI]: 2.59 to 9.38) increased risk of EC compared with those in the lowest quartile. The genetic or non-genetic model identified EC patients with AUCs ranging from 0.618 to 0.650. The combined model had an AUC of 0.707 (95% CI: 0.669 to 0.743) and was the best-fitting model (AIC = 750.55, BIC = 759.34). The NRI improved when the wGRS was added to the risk model with non-genetic factors only (NRI = 0.082, P = 0.037). CONCLUSIONS: Among the three risk models for EC, the combined model showed optimal predictive performance and can help to identify individuals at risk of EC for tailored preventive measures.

The cost-effectiveness of syphilis screening in pregnant women: a systematic literature review.

Introduction: The cost-effectiveness study of syphilis screening in pregnant women has not been synthesized. This study aimed to synthesize the economic evidence on the cost-effectiveness of syphilis screening in pregnant women that might contribute to making recommendations on the future direction of syphilis screening approaches. Methods: We systematically searched MEDLINE, PubMed, and Web of Science databases for relevant studies published before 19 January 2023 and identified the cost-effectiveness analyses for syphilis screening in pregnant women. The methodological design quality was appraised by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklist. Results: In total, 17 literature met the eligibility criteria for a full review. Of the 17 studies, four evaluated interventions using different screening methods, seven assessed a combination of syphilis testing and treatment interventions, three focused on repeat screening intervention, and four evaluated the interventions that integrated syphilis and HIV testing. The most cost-effective strategy appeared to be rapid syphilis testing with high treatment rates in pregnant women who were positive. Discussion: The cost-effectiveness of syphilis screening for pregnancy has been widely demonstrated. It is very essential to improve the compliance with maternal screening and the treatment rates for positive pregnant women while implementing screening.

The association between circulating 25-hydroxyvitamin D and pancreatic cancer: a systematic review and meta-analysis of observational studies.

PURPOSE: The relationship between circulating 25-hydroxyvitamin D [25(OH)D] and pancreatic cancer has been well studied but remains unclear. The purpose of this study was to elucidate the association between circulating 25(OH)D and pancreatic cancer by using a meta-analytic approach. METHODS: PubMed, Embase, and Wed of Science databases were searched through October 15, 2022. A random or fixed-effects model was used to estimate the pooled odds ratio (OR), risk ratio (RR), hazard ratio (HR) and their 95% confidence intervals (CIs). RESULTS: A total of 16 studies including 529,917 participants met the inclusion criteria, of which 10 reported incidence and 6 reported mortality. For the highest versus lowest categories of circulating 25(OH)D, the pooled OR of pancreatic cancer incidence in case-control studies was 0.98 (95% CI 0.69-1.27), and the pooled HRs of pancreatic cancer mortality in cohort and case-control studies were 0.64 (95% CI 0.45-0.82) and 0.78 (95% CI 0.62-0.95), respectively. The leave-one-out sensitivity analyses found no outliers and Galbraith plots indicated no substantial heterogeneity. CONCLUSION: Evidence from this meta-analysis suggested that high circulating 25(OH)D levels may be associated with decreased mortality but not incidence of pancreatic cancer. Our findings may provide some clues for the treatment of pancreatic cancer and remind us to be cautious about widespread vitamin D supplementation for the prevention of pancreatic cancer.

Assessing the causal association between dietary vitamin intake and lymphoma risk: a Mendelian randomisation study.

Observational studies of diet-related vitamins and lymphoma risk results were inconsistent. Our study aimed to estimate the causality between dietary vitamin intake and lymphoma through a Mendelian randomisation (MR) study. We enrolled dietary-related retinol, vitamin C, vitamin E, vitamin B6 and vitamin B12 as exposures of interest, with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) as the outcome. The causal effects were estimated using inverse variance weighting (IVW), MR-Egger regression analysis and weighted median, supplemented by sensitivity analyses. The results revealed that genetically predicted dietary vitamin B12 intake was associated with a reduced HL risk (OR = 0.22, 95% CI 0.05-0.91, p = 0.036). The Q test did not reveal heterogeneity, the MR-Egger test showed no significant intercepts, and the leave-one-out (LOO) analysis did not discover any SNP that affect the results. No causal relationship about dietary vitamin intake on the NHL risk was observed.

Trends, influencing factors and prediction analysis of under-five and maternal mortality rates in China from 1991 to 2020.

Introduction: Under-five mortality rate (U5MR) and maternal mortality rate (MMR) are important indicators for evaluating the quality of perinatal health and child health services in a country or region, and are research priorities for promoting maternal and infant safety and maternal and child health. This paper aimed to analysis and predict the trends of U5MR and MMR in China, to explore the impact of social health services and economic factors on U5MR and MMR, and to provide a basis for relevant departments to formulate relevant policies and measures. Methods: The JoinPoint regression model was established to conduct time trend analysis and describe the trend of neonatal mortality rate (NMR), infant mortality rate (IMR), U5MR and MMR in China from 1991 to 2020. The linear mixed effect model was used to assess the fixed effects of maternal health care services and socioeconomic factors on U5MR and MMR were explored, with year as a random effect to minimize the effect of collinearity. Auto regressive integrated moving average models (ARIMA) were built to predict U5MR and MMR from 2021 to 2025. Results: The NMR, IMR, U5MR and MMR from 1991 to 2020 in China among national, urban and rural areas showed continuous downward trends. The NMR, IMR, U5MR and MMR were significantly negatively correlated with gross domestic product (GDP), the proportion of the total health expenditure (THE) to GDP, system management rate, prenatal care rate, post-natal visit rate and hospital delivery rate. The predicted values of national U5MR from 2021 to 2025 were 7.3 ‰, 7.2 ‰, 7.1 ‰, 7.1 ‰ and 7.2 ‰ and the predicted values of national MMR were 13.8/100000, 12.1/100000, 10.6/100000, 9.6/100000 and 8.3/100000. Conclusion: China has made great achievements in reducing the U5MR and MMR. It is necessary for achieving the goals of Healthy China 2030 by promoting the equalization of basic public health services and further optimizing the allocation of government health resources. China's experience in reducing U5MR and MMR can be used as a reference for developing countries to realize the SDGs.

A novel autoantibody signatures for enhanced clinical diagnosis of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease that requires precise diagnosis for effective treatment. However, the diagnostic value of carbohydrate antigen 19 - 9 (CA19-9) is limited. Therefore, this study aims to identify novel tumor-associated autoantibodies (TAAbs) for PDAC diagnosis. METHODS: A three-phase strategy comprising discovery, test, and validation was implemented. HuProt™ Human Proteome Microarray v3.1 was used to screen potential TAAbs in 49 samples. Subsequently, the levels of potential TAAbs were evaluated in 477 samples via enzyme-linked immunosorbent assay (ELISA) in PDAC, benign pancreatic diseases (BPD), and normal control (NC), followed by the construction of a diagnostic model. RESULTS: In the discovery phase, protein microarrays identified 167 candidate TAAbs. Based on bioinformatics analysis, fifteen tumor-associated antigens (TAAs) were selected for further validation using ELISA. Ten TAAbs exhibited differentially expressed in PDAC patients in the test phase (P < 0.05), with an area under the curve (AUC) ranging from 0.61 to 0.76. An immunodiagnostic model including three TAAbs (anti-HEXB, anti-TXLNA, anti-SLAMF6) was then developed, demonstrating AUCs of 0.81 (58.0% sensitivity, 86.0% specificity) and 0.78 (55.71% sensitivity, 87.14% specificity) for distinguishing PDAC from NC. Additionally, the model yielded AUCs of 0.80 (58.0% sensitivity, 86.25% specificity) and 0.83 (55.71% sensitivity, 100% specificity) for distinguishing PDAC from BPD in the test and validation phases, respectively. Notably, the combination of the immunodiagnostic model with CA19-9 resulted in an increased positive rate of PDAC to 92.91%. CONCLUSION: The immunodiagnostic model may offer a novel serological detection method for PDAC diagnosis, providing valuable insights into the development of effective diagnostic biomarkers.

Diagnostic performance of anti-MAGEA family protein autoantibodies in esophageal squamous cell carcinoma.

MAGEA family proteins are immunogenic and can produce corresponding autoantibodies, and we aim to evaluate the diagnostic value of anti-MAGEA family protein autoantibodies in esophageal squamous cell carcinoma (ESCC). Protein chip was used to detect the expression level of anti-MAGEA autoantibodies (IgG and IgM) in 20 mixed serum samples. Enzyme linked immunosorbent assay was adopted to determine the expression level of autoantibodies in 1019 serum samples (423 ESCC, 423 healthy control (HC), 173 benign esophageal disease (BED)), and stepwise logistic regression analysis was used for developing a diagnostic model. Eight anti-MAGEA autoantibodies were screened out based on the protein chip. The levels of 7 autoantibodies (MAGEA1-IgG, MAGEA3-IgG, MAGEA3-IgM, MAGEA4-IgG, MAGEA6-IgG, MAGEA10-IgG, MAGEA12-IgG) in ESCC were significantly higher than that in HC, and the levels of anti-MAGEA1 IgG, anti-MAGEA3-IgG, anti-MAGEA4-IgG, anti-MAGEA10-IgG and anti-MAGEA12-IgG autoantibodies in ESCC group were significantly higher than those in BED group. The area under curve (AUC), sensitivity and specificity of the logistic regression model (MAGEA1-IgG, MAGEA4-IgG, MAGEA6-IgG, MAGEA12-IgG) in the training set and the validation set were 0.725 and 0.698, 55.2% and 51.8%, 80.4% and 84.5%, respectively, in distinguishing ESCC and HC. The model also could distinguish between ESCC and BED, with the AUC of 0.743, sensitivity of 55.4% and specificity of 89.0%. The positive rate of the model combined with cytokeratin 19 fragment to diagnose ESCC reached 78.0%. The study identified anti-MAGEA autoantibodies with potential diagnostic value for ESCC, which may provide new promising for the detection of the disease.

Factors associated with adverse pregnancy outcomes of maternal syphilis in Henan, China, 2016-2022.

Maternal syphilis not only seriously affects the quality of life of pregnant women themselves but also may cause various adverse pregnancy outcomes (APOs). This study aimed to analyse the association between the related factors and APOs in maternal syphilis. 7,030 pregnant women infected with syphilis in Henan Province between January 2016 and December 2022 were selected as participants. Information on their demographic and clinical characteristics, treatment status, and pregnancy outcomes was collected. Multivariate logistic regression models and chi-squared automatic interaction detector (CHAID) decision tree models were used to analyse the factors associated with APOs. The multivariate logistic regression results showed that the syphilis infection history (OR = 1.207, 95% CI, 1.035-1.409), the occurrence of abnormality during pregnancy (OR = 5.001, 95% CI, 4.203-5.951), not receiving standard treatment (OR = 1.370, 95% CI, 1.095-1.716), not receiving any treatment (OR = 1.313, 95% CI, 1.105-1.559), and a titre ≥1:8 at diagnosis (OR = 1.350, 95%CI, 1.079-1.690) and before delivery (OR = 1.985, 95%CI, 1.463-2.694) were risk factors. A total of six influencing factors of APOs in syphilis-infected women were screened using the CHAID decision tree model. Integrated prevention measures such as early screening, scientific eugenics assessment, and standard syphilis treatment are of great significance in reducing the incidence of APOs for pregnant women infected with syphilis.

Identification of novel tumor-associated antigens and evaluation of a panel of autoantibodies in detecting oral cancer.

BACKGROUND: We aimed to identify tumor-associated antigen (TAA) biomarkers through bioinformatic analysis and experimental verification, and to evaluate a panel of autoantibodies against tumor-associated antigens (TAAbs) for the detection of oral cancer (OC). METHODS: GEO and TCGA databases were used to screen significantly up-regulated genes related to OC, and protein-protein interaction (PPI) analysis and Cystoscope software were used to identify key genes. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of autoantibodies in 173 OC patients and 173 normal controls, and binary logistic regression analysis was used to build a diagnostic model. RESULTS: Using bioinformatics, we identified 10 key genes (AURKA, AURKB, CXCL8, CXCL10, COL1A1, FN1, FOXM1, MMP9, SPP1 and UBE2C) that were highly expressed in OC. Three autoantibodies (anti-AURKA, anti-CXCL10, anti-FOXM1) were proven to have diagnostic value for OC in the verification set and the validation set. The combined assessment of these three autoantibodies improved the diagnostic value for OC, with an area under the curve (AUC), sensitivity and specificity of 0.741(95%CI:0.690-0.793),58.4% and 80.4%, respectively. In addition, the combination of these three autoantibodies also had high diagnostic value for oral squamous cell carcinoma (OSCC), with an AUC, sensitivity and specificity of 0.731(95%CI:0.674,0.786), 53.8% and 82.1%, respectively. CONCLUSIONS: Our study revealed that AURKA, CXCL10 and FOXM1 may be potential biomarkers and the panel of three autoantibodies (anti-AURKA, anti-CXCL10 and anti-FOXM1) had good diagnostic value for OC.

A panel of autoantibodies against multiple tumor-associated antigens in the immunodiagnosis of esophageal squamous cell cancer.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in China with very low 5-year survival rate mostly due to the paucity of effective early diagnostic methods. Serum autoantibodies against 9 tumor-associated antigens (TAAs) from ESCC patients and healthy controls were detected by enzyme-linked immunosorbent assay to evaluate their performances in the immunodiagnosis of ESCC. Logistic regression models were generated to predict the probability of individuals being diagnosed with ESCC in training cohort (648 participants) and further validated in another independent cohort (372 participants). Finally, a panel of four TAAs showed high diagnostic accuracy with areas under the receiver operating characteristic curve of 0.838 in training cohort and 0.872 in validation cohort, respectively. The percentages of individuals correctly classified were 77.01 % in training cohort and 78.49 % in validation cohort, respectively. This model could discriminate early-stage (AJCC stage 0, I and II) ESCC patients from normal controls, with true-positive rate (TPR) of 67.57 % in training cohort and TPR of 63.33 % in validation cohort, and the overall TPR for early-stage ESCC was 66.85 % when the two cohorts were combined. The diagnostic performance of this model showed no significant difference between early-stage and late-stage (AJCC stage III and IV) ESCC patients. In summary, the optimized model with 4 TAAs has a high diagnostic performance for ESCC detection, especially for early-stage ESCC.

Serum autoantibodies in the early detection of esophageal cancer: a systematic review.

Antibodies against tumor-associated antigens (TAAs) have been found in serum of patients with various types of cancers and may serve as biomarkers for early detection of esophageal cancer as well. This systematic review aims to give an overview about known autoantibodies and their diagnostic value in esophageal cancer. We conducted a systematic literature search in two databases to identify studies which performed serological testing for autoantibodies in esophageal cancer patients and controls. Data on study characteristics and results were extracted independently by two reviewers. Overall, 45 articles reporting the detection of 35 different autoantibodies met the inclusion criteria of this review. The most common antibody detection method was enzyme-linked immunosorbent assay (ELISA), and the most frequently assessed autoantibody was anti-p53, which was tested in 17 studies and for 15 studies of which a meta-analysis was conducted to comprehensively evaluate the diagnostic value. Most antibodies were assessed in only one study, and only few authors have evaluated the diagnostic value of combinations of multiple autoantibodies. For single autoantibodies, specificity was generally very high (median 98.3 %), but sensitivity was mostly rather low (median 26.7 %). For some autoantibody combinations, substantially higher sensitivity at reasonably high levels of specificity could be achieved. Development of extended and optimized multimarker panels of autoantibodies might be a promising approach for esophageal cancer early detection.

Mini-array of multiple tumor-associated antigens (TAAs) in the immunodiagnosis of esophageal cancer.

Sera of cancer patients may contain antibodies that react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). The present study aimed to determine whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach in esophageal cancer detection and diagnosis. Our mini-array of multiple TAAs consisted of eleven antigens, p53, pl6, Impl, CyclinB1, C-myc, RalA, p62, Survivin, Koc, CyclinD1 and CyclinE full-length recombinant proteins. Enzyme-linked immunosorbent assays (ELISA) were used to detect autoantibodies against eleven selected TAAs in 174 sera from patients with esophageal cancer, as well as 242 sera from normal individuals. In addition, positive results of ELISA were confirmed by Western blotting. In a parallel screening trial, with the successive addition of antigen to a final total of eleven TAAs, there was a stepwise increase in positive antibody reactions. The eleven TAAs were the best parallel combination, and the sensitivity and specificity in diagnosing esophageal cancer was 75.3% and 81.0%, respectively. The positive and negative predictive values were 74.0% and 82.0%, respectively, indicating that the parallel assay of eleven TAAs raised the diagnostic precision significantly. In addition, the levels of antibodies to seven antigens, comprising p53, Impl, C-myc, RalA, p62, Survivin, and CyclinD1, were significantly different in various stages of esophageal cancer, which showed that autoantibodies may be involved in the pathogenesis and progression of esophageal cancer. All in all, this study further supports our previous hypothesis that a combination of antibodies might acquire higher sensitivity for the diagnosis of certain types of cancer. A customized mini-array of multiple carefully-selected TAAs is able to enhance autoantibody detection in the immunodiagnosis of esophageal cancer and autoantibodies to TAAs might be reference indicators of clinical stage.