Maternal Oxidative Balance Score during Pregnancy and Congenital Heart Defects.

The relationship between maternal oxidative balance score (OBS) in pregnancy, representing overall oxidative balance status by integrating dietary and lifestyle factors, and congenital heart defects (CHD) remains unclear; therefore, this study attempted to explore their associations among the Chinese population. We conducted a case-control study including 474 cases and 948 controls in Northwest China. Pregnant women were interviewed to report diets and lifestyles in pregnancy by structured questionnaires. Logistic regression models were used to estimate the adjusted ORs (95%CIs). Maternal OBS ranged from 6 to 34 among cases, and 5 to 37 among controls. Comparing the highest with the lowest tertile group, the adjusted OR for CHD was 0.31 (0.19-0.50). The CHD risk was reduced by 7% (OR = 0.93, 95%CI = 0.90-0.95) in association with per 1 higher score of OBS during pregnancy. The inverse relationship between maternal OBS and CHD risk appeared to be more pronounced among participants in urban areas (OR = 0.89, 95%CI = 0.86-0.93). Maternal OBS during pregnancy showed good predictive values for fetal CHD, with the areas under the receiver operating characteristic curve 0.78 (0.76-0.81). These findings highlighted the importance of reducing oxidative stress through antioxidant-rich diets and healthy lifestyles among pregnant women to prevent fetal CHD.

Network pharmacology and molecular docking reveal the mechanisms of curcumin activity against esophageal squamous cell carcinoma.

Background: Curcumin (CUR), an effective traditional Chinese medicinal extract, displays good anti-cancer activity against various cancers. Nevertheless, the impacts and fundamental mechanisms of CUR to treat esophageal squamous cell carcinoma (ESCC) yet to be comprehensively clarified. This study examined the suppressive impacts of CUR on ESCC. Methods: For a comprehensive understanding of the effect of CUR in ESCC. The CUR targets and ESCC-related genes were identified respectively, and the intersection targets between CUR and ESCC were acquired. Then, we examined the intersection targets and discovered genes that were expressed differently in ESCC. Using DAVID, enrichment analyses were conducted on the targets of CUR-ESCC. The STRING database and Cytoscape v.3.9.1 were utilized to build networks for protein-protein interaction (PPI) and drug-target-pathway. Furthermore, the interactions between CUR and its core targets were confirmed by molecular docking studies. To confirm the effects of CUR on ESCC cells, in vitro experiments were finally conducted. Results: Overall, 47 potential CUR targets for ESCC treatment were identified. The KEGG pathway enrichment analysis identified 61 signaling pathways, primarily associated with the FoxO signaling, the cell cycle, cellular senescence, the IL-17 signaling pathway which play important roles in ESCC progression. In the PPI network and the docking results identified CHEK1 and CDK6 as the core targets that positively associated with ESCC survival. CUR arrested ESCC cells at the G2/M and S phases, as shown by flow cytometry. Colony formation and CCK8 assays showed that CUR can inhibit the proliferative ability of ESCC cells. The Transwell invasion results validated that CUR can significantly inhibit the invasion rates of ESCC cells. Conclusion: Collectively, these findings indicate that CUR exhibits pharmacological effects on multiple targets and pathways in ESCC.

Gastric cancer immunotherapy: A scientometric and clinical trial review.

This letter is intended to arouse your interest in a recent review of comprehensive scientometrics and clinical trials on immunotherapy for gastric cancer (GC). Our study reviews recent advances in immunotherapy in the field of GC and highlights its new prospects as a treatment for GC. Our research reveals China's leadership in this field, as well as new therapeutic strategies such as immune checkpoint inhibitors, cellular immunotherapy, and vaccines. The combined findings highlight the potential of immunotherapy to improve survival and quality of life in patients with stomach cancer. We believe that this study will provide important guidance for the future direction of the GC treatment field.

Dietary Inflammatory Index during Pregnancy and Congenital Heart Defects.

The relationship between diet-related inflammation during pregnancy and congenital heart defects (CHD) is unclear. This study attempted to investigate the association between the dietary inflammation index (DII) during pregnancy, reflecting the overall inflammatory potential of the maternal diet, and CHD in Northwest China. A case-control study with 474 cases and 948 controls was performed in Xi'an City, China. Eligible women awaiting delivery were recruited, and their dietary and other information during pregnancy was collected. Logistic regression models were applied to estimate the risk of CHD in association with DII. The maternal DII ranged from -1.36 to 5.73 in cases, and 0.43 to 5.63 in controls. Pregnant women with per 1 higher DII score were at 31% higher risk of fetal CHD (OR = 1.31, 95%CI = 1.14-1.51), and the adjusted OR (95%CI) comparing the pro-inflammatory diet group with the anti-inflammatory diet group was 2.04 (1.42-2.92). The inverse association of maternal DII score with CHD risk was consistent across various subgroups of maternal characteristics. Maternal DII in pregnancy had good predictive value for CHD in offspring, with the areas under the receiver operating characteristic curve higher than 0.7. These findings suggested that avoiding a pro-inflammatory diet in pregnancy should be emphasized in the prevention of CHD.

Integrative analysis of platelet-related genes for the prognosis of esophageal cancer.

BACKGROUND: Every year, esophageal cancer is responsible for 509000 deaths and around 572000 new cases worldwide. Although esophageal cancer treatment options have advanced, patients still have a dismal 5-year survival rate. AIM: To investigate the relationship between genes associated to platelets and the prognosis of esophageal cancer. METHODS: We searched differentially expressed genes for changes between 151 tumor tissues and 653 normal, healthy tissues using the "limma" package. To develop a prediction model of platelet-related genes, a univariate Cox regression analysis and least absolute shrinkage and selection operator Cox regression analysis were carried out. Based on a median risk score, patients were divided into high-risk and low-risk categories. A nomogram was created to predict the 1-, 2-, and 3-year overall survival (OS) of esophageal cancer patients using four platelet-related gene signatures, TNM stages, and pathological type. Additionally, the concordance index, receiver operating characteristic curve, and calibration curve were used to validate the nomogram. RESULTS: The prognosis of esophageal cancer was associated to APOOL, EP300, PLA2G6, and VAMP7 according to univariate Cox regression analysis and least absolute shrinkage and selection operator regression analysis. Patients with esophageal cancer at high risk had substantially shorter OS than those with cancer at low risk, according to a Kaplan-Meier analysis (P < 0.05). TNM stage (hazard ratio: 2.187, 95% confidence interval: 1.242-3.852, P = 0.007) in both univariate and multivariate Cox regression and risk score were independently correlated with OS (hazard ratio: 2.451, 95% confidence interval: 1.599-3.756, P < 0.001). CONCLUSION: A survival risk score model and independent prognostic variables for esophageal cancer have been developed using APOOL, EP300, PLA2G6, and VAMP7. OS for esophageal cancer might be predicted using the nomogram based on TNM stage, pathological type, and risk score. The nomogram demonstrated strong predictive ability, as shown by the concordance index, receiver operating characteristic curve, and calibration curve.

Comprehensive analysis of the relationship between cuproptosis-related genes and esophageal cancer prognosis.

BACKGROUND: Esophageal cancer is one of the most common malignant tumors of the digestive system, with a 5-year survival rate of 15% to 50%. Cuproptosis, a unique kind of cell death driven by protein lipoylation, is strongly connected to mitochondrial metabolism. The clinical implications of cuproptosis-related genes in esophageal cancer, however, are mainly unknown. AIM: To identify cuprotosis-related genes that are differentially expressed in esophageal cancer and investigate their prognostic significance. METHODS: With |log fold change| > 1 and false discovery rate < 0.05 as criteria, the Wilcox test was used to evaluate the differentially expressed genes between 151 tumor tissues and 151 normal esophageal tissues. Cuproptosis-related genes were selected to be linked with prognosis using univariate Cox regression analysis. Genes were separated into high- and low- expression groups based on their cutoff value of gene expression, and the correlation between the two groups and overall survival or progression-free survival was investigated using the log-rank test. The C-index, calibration curve, and receiver operator characteristic (ROC) curve were used to assess a nomogram containing clinicopathological characteristics and cuproptosis-related genes. RESULTS: Pyruvate dehydrogenase A1 (PDHA1) was found to be highly correlated with prognosis in univariate Cox regression analysis (hazard ratio = 22.96, 95% confidence interval = 3.09-170.73; P = 0.002). According to Kaplan-Meier survival curves, low expression of PDHA1 was associated with a better prognosis (log-rank P = 0.0007). There was no significant correlation between PDHA1 expression and 22 different types of immune cells. Tumor necrosis factor superfamily member 15 (TNFSF15) (P = 3.2 × 10-6; r = 0.37), TNFRSF14 (P = 8.1 × 10-8; r = 0.42), H long terminal repeat-associating 2 (P = 6.0 × 10-8; r = 0.42) and galectin 9 (P = 3.1 × 10-6; r = 0.37) were all found to be considerably greater in the high PDHA1 expression group, according to an analysis of genes related to 47 immunological checkpoints. The low PDHA1 expression group had significantly lower levels of cluster of differentiation 44 (CD44) (P = 0.00028; R = -0.29), TNFRSF18 (P = 1.2 × 10-5; R = -0.35), programmed cell death 1 ligand 2 (P = 0.0032; R = -0.24), CD86 (P = 0.018; R = -0.19), and CD40 (P = 0.0047; R = -0.23), and the differences were statistically significant. We constructed a prognostic nomogram incorporating pathological type, tumor-node-metastasis stage, and PDHA1 expression, and the C-index, calibration curve, and ROC curve revealed that the nomogram's predictive performance was good. CONCLUSION: Cuproptosis-related genes can be used as a prognostic predictor for esophageal cancer patients, providing novel insights into cancer treatment.

Pyroptosis-related genes play a significant role in the prognosis of gastric cancer.

BACKGROUND: Pyroptosis is an inflammatory form of programmed cell death, which has been shown to be related to the prognosis of many tumors. However, its role in gastric cancer (GC) is not fully understood. AIM: To evaluate the expression of pyroptosis-related genes in GC and its correlation with prognosis. METHODS: We constructed prognostic multigene markers of differentially expressed genes associated with pyroptosis by least absolute contraction and selection operator Cox regression. The risk model was analyzed by Kaplan-Meier curve, two-sided log-rank test and functional enrichment analysis. RESULTS: Sixty-three pyroptosis-related genes were differentially expressed in tumor tissues and adjacent nontumor tissues. Based on these differentially expressed genes, 5 gene signature were constructed and all GC patients were classified into two risk groups. Kaplan-Meier survival curve showed that the overall survival (OS) of patients in the high-risk group was significantly lower than that of the low-risk group. Multivariate Cox regression analyses showed that the risk score was an independent risk factor for OS. Receiver operating characteristic curve analysis confirmed the predictive ability of the model. External validation indicated increased OS in the low-risk group. The immune function and immune cell scores of the high-risk group were generally higher than those of the low-risk group. CONCLUSION: Pyroptosis-related genes play a significant role in tumor immune microenvironment. This novel model, which contains 5 pyroptosis-related genes, is an independent predicting factor for OS in GC patients, and may help to evaluate the prognosis of GC.

Development and validation of an epithelial-mesenchymal transition-related gene signature for predicting prognosis.

BACKGROUND: Currently, there are many therapeutic methods for lung adenocarcinoma (LUAD), but the 5-year survival rate is still only 15% at later stages. Epithelial- mesenchymal transition (EMT) has been shown to be closely associated with local dissemination and subsequent metastasis of solid tumors. However, the role of EMT in the occurrence and development of LUAD remains unclear. AIM: To further elucidate the value of EMT-related genes in LUAD prognosis. METHODS: Univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses were applied to establish and validate a new EMT-related gene signature for predicting LUAD prognosis. The risk model was evaluated by Kaplan-Meier survival analysis, principal component analysis, and functional enrichment analysis and was used for nomogram construction. The potential structures of drugs to which LUAD is sensitive were discussed with respect to EMT-related genes in this model. RESULTS: Thirty-three differentially expressed genes related to EMT were found to be highly associated with overall survival (OS) by using univariate Cox regression analysis (log2FC ≥ 1, false discovery rate < 0.001). A prognostic signature of 7 EMT-associated genes was developed to divide patients into two risk groups by high or low risk scores. Kaplan-Meier survival analysis showed that the OS of patients in the high-risk group was significantly poorer than that of patients in the low-risk group (P < 0.05). Multivariate Cox regression analysis showed that the risk score was an independent risk factor for OS (HR > 1, P < 0.05). The results of receiver operator characteristic curve analysis suggested that the 7-gene signature had a perfect ability to predict prognosis (all area under the curves > 0.5). CONCLUSION: The EMT-associated gene signature classifier could be used as a feasible indicator for predicting OS.

Epidemiological and clinical characteristics of road traffic crashes related thoracic traumas: analysis of 5095 hospitalized chest injury patients.

BACKGROUND: Road traffic crashes related (RTCR) chest traumas remain important global public health challenge. The impact of boosting market of automobile vehicles in China during last decade on thoracic injury needs to be defined. This study aimed to review and analyze the demographic and clinical characteristics of RTCR thoracic injuries in China. METHODS: Clinical records of patients with thoracic trauma admitted to thoracic surgery department between January 2003 and June 2020 were retrospectively retrieved and reviewed. Patients' profiles and clinical characteristics were comparatively analyzed between road traffic crashes caused injury and other injury mechanisms, and in RTCR chest trauma patients before January 2011 (2003 group), and after January 2011 (2011 group), when is considered as the beginning year of Chinese household vehicle era. RESULTS: The study included 5095 thoracic trauma patients with mean age of 50.2 years, of whom 79.4% were male. Most of the patients (70.3%, n = 3583) had rib fractures. Associated injuries were present in 52.0% of the patients, of them 78.5% (n = 2080) were extremity fractures. Road traffic crashes accounted for 41.4% (n = 2108) of the injuries, most of them (98.0%) were related to motor vehicles. In comparison with other chest trauma mechanisms, RTCR chest injuries affected females and older males more frequently, with a higher incidence of rib fractures and sternum fractures, and higher injury severity scores (ISS) (all p < 0.05). Surgeries were required in 1495 (70.9%) patients of the RRTCR chest traumas, while the majority of non-RTCR thoracic injuries were managed conservatively or with tube thoracostomy (30.2%, n = 901). RTCR chest traumas caused longer hospital stay (13.0 ± 9.6 days vs. 11.8 ± 7.4 days, p = 0.001), higher ICU usage (30.7% vs. 19.6%, p = 0.001), higher rate of ventilator support (12.9% vs. 7.5%, p = 0.001), and higher mortalities (3.8% vs. 1.6%, p = 0.005) than that of non-RTRA chest injuries. For RTCR patients, when compared with 2003 group, 2011 group had similar patterns in terms of accident category, associated injury and treatment. However, 2011 group had more females (38.5% vs. 18.0%, p = 0.001) and older males (50.6 ± 9.7 vs. 47.9 ± 17.2, p = 0.001), with a higher ISS (18.3 ± 10.2 vs. 17.1 ± 8.9, p = 0.004), and fewer were managed with chest tubes (25.0% vs. 29.2%, p = 0.031). Clinical outcomes were not significantly different between the groups in terms of hospital length of stay, intensive care unit (ICU) usage, ICU length of stay, duration of ventilator hours and mortality. However, the 2011 group had more patients requiring ventilator support (14.4% vs. 10.6%, p = 0.011). CONCLUSIONS: Road traffic crashes remain to be the major etiology of thoracic injuries in China, which usually affects middle-aged males, causing rib fractures with concomitant injuries frequently occurring to other organ systems. Treatments mainly include tube thoracotomy and surgical procedures. Although the clinical characteristics and outcomes of traffic accident related chest traumas are largely unchanged in spite of the rapid increasing numbers of motor vehicles, variations in the pattern of injuries by gender, age, injury severity and ventilator usage may still provide important information for targeted management.

Development of a lipid metabolism-related gene model to predict prognosis in patients with pancreatic cancer.

BACKGROUND: Pancreatic cancer is a highly heterogeneous disease, making prognosis prediction challenging. Altered energy metabolism to satisfy uncontrolled proliferation and metastasis has become one of the most important markers of tumors. However, the specific regulatory mechanism and its effect on prognosis have not been fully elucidated. AIM: To construct a prognostic polygene signature of differentially expressed genes (DEGs) related to lipid metabolism. METHODS: First, 9 tissue samples from patients with pancreatic cancer were collected and divided into a cancer group and a para-cancer group. All patient samples were subjected to metabolomics analysis based on liquid tandem chromatography quadrupole time of flight mass spectrometry. Then, mRNA expression profiles and corresponding clinical data of pancreatic cancer were downloaded from a public database. Least absolute shrinkage and selection operator Cox regression analysis was used to construct a multigene model for The Cancer Genome Atlas. RESULTS: Principal component analysis and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) based on lipid metabolomics analysis showed a clear distribution in different regions. A Euclidean distance matrix was used to calculate the quantitative value of differential metabolites. The permutation test of the OPLS-DA model for tumor tissue and paracancerous tissue indicated that the established model was consistent with the actual condition based on sample data. A bar plot showed significantly higher levels of the lipid metabolites phosphatidylcholine (PC), phosphatidyl ethanolamine (PE), phosphatidylethanol(PEtOH), phosphatidylmethanol (PMeOH), phosphatidylserine (PS) and diacylglyceryl trimethylhomoserine (DGTS) in tumor tissues than in paracancerous tissues. According to bubble plots, PC, PE, PEtOH, PMeOH, PS and DGTS were significantly higher in tumor tissues than in paracancerous tissues. In total, 12.3% (25/197) of genes related to lipid metabolism were differentially expressed between tumor tissues and adjacent paracancerous tissues. Six DEGs correlated with overall survival in univariate Cox regression analysis (P < 0.05), and a 4-gene signature model was developed to divide patients into two risk groups, with patients in the high-risk group having significantly lower overall survival than those in the low-risk group (P < 0.05). ROC curve analysis confirmed the predictive power of the model. CONCLUSION: This novel model comprising 4 lipid metabolism-related genes might assist clinicians in the prognostic evaluation of patients with pancreatic cancer.

Author Correction: A new treatment strategy for end-stage hepatic alveolar echinococcosis: IVC resection without reconstruction.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Retraction Note: The diagnostic nomogram of platelet-based score models for hepatic alveolar echinococcosis and atypical liver cancer.

Editor's Note: this Article has been retracted; the Retraction Note is available at https://www.nature.com/articles/s41598-020-73758-x.

Relationship between platelet-based models and the prognosis of patients with malignant hepatic tumors.

Platelets (PLTs) are involved in tumor growth, metabolism and vascular activation. PLT-based models have been reported to have significant value on the recurrence of malignant hepatic tumors. The present study aimed to investigate the effect of PLT count and 18 PLT-based models on the prognosis of patients with malignant hepatic tumors. The clinical data from 189 patients with malignant hepatic tumors were retrospectively analyzed and used to calculate the scores of the 18 PLT-based models. Receiver operating characteristic curve was used to determine the suitable cut-off values of mortality and recurrence in patients with malignant hepatic tumors. The overall survival and cumulative recurrence rates of patients were calculated using Kaplan-Meier survival curves and the difference was analyzed using log-rank test. Multivariate analysis was performed to determine the independent risk factors of recurrence-free survival and overall survival. In the present study, 11 models were considered as predictors of mortality (P<0.05) and six models were considered as predictors of recurrence (P<0.05). The results from multivariate analysis demonstrated that vascular cancer embolus, uric acid >231 µmol/l, hemoglobin >144 g/l and the Lok index model >0.695 were considered as independent risk factors of mortality (P<0.05). Furthermore, vascular cancer embolus, PLT to lymphocyte ratio (PLR) >175 and fibrosis-4 (FIB-4) >4.82 were independent factors of recurrence (P<0.05). In addition, the results from this study indicated that the Lok-index could be considered as a predictor of the overall survival rate. In conclusion, the FIB-4 and PLR model may be valuable for predicting the recurrence-free rate of patients with malignant hepatic tumors.

The diagnostic nomogram of platelet-based score models for hepatic alveolar echinococcosis and atypical liver cancer.

Hepatic alveolar echinococcosis (HAE) and liver cancer had similarities in imaging results, clinical characteristics, and so on. And it is difficult for clinicians to distinguish them before operation. The aim of our study was to build a differential diagnosis nomogram based on platelet (PLT) score model and use internal validation to check the model. The predicting model was constructed by the retrospective database that included in 153 patients with HAE (66 cases) or liver cancer (87 cases), and all cases was confirmed by clinicopathology and collected from November 2011 to December 2018. Lasso regression analysis model was used to construct data dimensionality reduction, elements selection, and building prediction model based on the 9 PLT-based scores. A multi-factor regression analysis was performed to construct a simplified prediction model, and we added the selected PLT-based scores and relevant clinicopathologic features into the nomogram. Identification capability, calibration, and clinical serviceability of the simplified model were evaluated by the Harrell's concordance index (C-index), calibration plot, receiver operating characteristic curve (ROC), and decision curve. An internal validation was also evaluated by the bootstrap resampling. The simplified model, including in 4 selected factors, was significantly associated with differential diagnosis of HAE and liver cancer. Predictors of the simplified diagnosis nomogram consisted of the API index, the FIB-4 index, fibro-quotent (FibroQ), and fibrosis index constructed by King's College Hospital (King's score). The model presented a perfect identification capability, with a high C-index of 0.929 (0.919 through internal validation), and good calibration. The area under the curve (AUC) values of this simplified prediction nomogram was 0.929, and the result of ROC indicated that this nomogram had a good predictive value. Decision curve analysis showed that our differential diagnosis nomogram had clinically identification capability. In conclusion, the differential diagnosis nomogram could be feasibly performed to verify the preoperative individualized diagnosis of HAE and liver cancer.

A new treatment strategy for end-stage hepatic alveolar echinococcosis: IVC resection without reconstruction.

Patients with hepatic alveolar echinococcosis (HAE) infringing on the inferior vena cava (IVC) have a poor prognosis when radical resection cannot be performed because curative resection is limited by IVC reconstruction. There is little information concerning combined resection of the liver and the IVC. This study explored a novel treatment method for HAE infringing on the IVC and evaluated the safety and feasibility of combined resection of the liver and the IVC. A total of 13 patients were treated with liver resection combined with IVC resection for end-stage HAE between January 2016 and July 2018 at the Affiliated Hospital of Qinghai University. The demographic, clinical, and follow-up data were collected and analysed. The 13 patients underwent resection of the IVC without reconstruction. Of these, 3 exhibited oedema of both lower limbs and the scrotum (23.1%), 2 exhibited pneumothorax (15.4%), 1 exhibited bile leakage (7.7%), 1 exhibited bacteraemia (7.7%), and 1 developed abdominal haemorrhage that was stopped with conservative treatment (7.7%). There was 1 case of operation-related mortality because of upper gastrointestinal haemorrhage (7.7%), and no patients developed recurrence or had residual lesions. Liver resection combined with IVC resection is effective and feasible for patients with HAE infringing on the IVC.