The prognostic value of co-expression of stemness markers CD44 and CD133 in endometrial cancer.

Objective: The purpose of this study was to investigate the correlation between stemness markers (CD44 and CD133) and clinical pathological features, and to further explore the prognostic value of co-expression of CD44 & CD133 in endometrial cancer (EC). Methods: Clinical data of stage I-III EC patients who underwent initial surgical treatment at two large tertiary medical centers from 2015 to 2020 were retrospectively collected. Cohen's kappa coefficient was used to show the consistency of the expression between CD44 and CD133. The correlation between co-expression of CD44 & CD133 and prognosis of EC patients was explored using univariate and multivariate Cox regression analysis. Then, the prognosis models for early-stage (stage I-II) EC patients were constructed. Finally, stratified analysis was performed for EC patients in high-intermediate-risk and high-risk groups, Kaplan-Meier analysis was used to compare the survival differences between patients with and without adjuvant therapy in different co-expression states (low expression, mixed expression, high expression) of CD44 & CD133. Results: A total of 1168 EC patients were included in this study. The consistency of the expression between CD44 and CD133 was 70.5%, the kappa coefficient was 0.384. High expression of CD44 & CD133 was associated with early FIGO stage (P=0.017), superficial myometrial invasion (P=0.017), and negative lymphatic vessel space invasion (P=0.017). Cox regression analysis showed that the co-expression of CD44 & CD133 was significantly correlated with the prognosis of early-stage (stage I-II) patients (P=0.001 for recurrence and P=0.005 for death). Based on this, the nomogram models were successfully constructed to predict the prognosis of early-stage EC patients. Meanwhile, Kaplan-Meier analysis showed that patients with adjuvant therapy had a better overall prognosis than those without adjuvant therapy in high-intermediate-risk and high-risk groups. However, there was no statistically significant difference in survival between patients with and without adjuvant therapy in high expression of CD44 & CD133 group (P=0.681 for recurrence, P=0.621 for death). Conclusion: High expression of CD44 & CD133 was closely related to the adverse prognosis of early-stage EC patients. Meanwhile, patients with high expression of CD44 & CD133 may not be able to achieve significant survival benefits from adjuvant therapy.

Analysis of global gene expression using RNA-sequencing reveals novel mechanism of Yanghe Pingchuan decoction in the treatment of asthma.

BACKGROUND: Yanghe Pingchuan decoction (YPD) has been used for asthma treatment for many years in China. We sought to understand the mechanism of YPD, and find more potential targets for YPD-based treatment of asthma. METHODS: An ovalbumin-induced asthma model in rats was created. Staining (hematoxylin and eosin, Masson) was used to evaluate the treatment effect of YPD. RNA-sequencing was carried out to analyze global gene expression, and differentially expressed genes (DEGs) were identified. Analysis of the functional enrichment of genes was done using the Gene Ontology database (GO). Analysis of signaling-pathway enrichment of genes was done using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Real-time reverse transcription-quantitative polymerase chain reaction was undertaken to measure expression of DEGs. RESULTS: Pathology showed that YPD had an improvement effect on rats with asthma. RNA-sequencing showed that YPD led to upregulated and downregulated expression of many genes. The YPD-based control of asthma pathogenesis may be related to calcium ion (Ca2+) binding, inorganic cation transmembrane transporter activity, microtubule motor activity, and control of canonical signaling (e.g., peroxisome proliferator-activated receptor, calcium, cyclic adenosine monophosphate). Enrichment analyses suggested that asthma pathogenesis may be related to Ca2 + binding and contraction of vascular smooth muscle. A validation experiment showed that YPD could reduce the Ca2 + concentration by inhibiting the Angiopoietin-II (Ang-II)/Phospholipase (PLA)/calmodulin (CaM0 signaling axis. CONCLUSION: Control of asthma pathogenesis by YPD may be related to inhibition of the Ang-II/PLA/CaM signaling axis, reduction of the Ca2+ concentration, and relaxation of airway smooth muscle (ASM).

Yanghe Pingchuan granules mitigates oxidative stress and inflammation in a bronchial asthma rat model: role of the IKK/IκB/NF-κB signalling pathway.

Background: Bronchial asthma (BA) is a chronic inflammatory airway disease. Previous research has shown that Yanghe Pingchuan granules (YPG), among the granules formulated by the First Affiliated Hospital of the Anhui University of Chinese Medicine, exerts a precise therapeutic effect on BA. We previously showed that YPG improves airway inflammation in BA rats. Other studies have shown that the inhibitor of kappa-B kinase (IKK)/inhibitor of NF-κB (IκB)/nuclear factor kappa-B (NF-κB) signalling pathway plays a key role in inflammation mediation. Therefore, this study explored whether YPG could intervene in BA through the IKK/IκB/NF-κB signalling pathway. Methods: Ovalbumin-induced method was used to established BA rat model. After successful modelling, the authors used YPG to intervene the rats in BA rats. Hematoxylin-eosin (HE) staining was used to detect the bronchial pathological changes in BA rats, enzyme-linked immunosorbent assay (ELISA) was used to detect the changes of inflammatory factors (IL-1ß and IL-6) and oxidative stress indexes malondialdehyde (MDA), superoxide dismutase (SOD) and nitrogen monoxide (NO), Quantitative real-time polymerase chain reactionCR and western blot were used to detect the expression of IKK/IκB/NF-κB signalling pathway. Results: In BA model rats, YPG significantly improved the inflammatory response in bronchial tissues, reduced inflammatory factors IL-1ß and IL-6, alleviated oxidative stress, reduced MDA and NO, and increased SOD. Quantitative real-time polymerase chain reaction and western blot results showed that YPG could block the IKK/IκB/NF-κB signalling pathway. Conclusion: These findings showed that YPG had a definite therapeutic effect on BA, which may be related to blocking the IKK/IκB/NF-κB signalling pathway and improving inflammation and oxidative stress.

Investigating the mechanism of action of Yanghe Pingchuan Granule in the treatment of bronchial asthma based on bioinformatics and experimental validation.

Background: Yanghe Pingchuan Granule (YPG) is a patented Chinese medicine developed independently by the Anhui Provincial Hospital of Traditional Chinese Medicine. For many years, it has been used for the treatment of asthma with remarkable clinical effects. However, the composition of YPG is complex, and its potential active ingredients and mechanism of action for the treatment of asthma are unknown. Materials and methods: In this study, we investigated the potential mechanism of action of YPG in the treatment of asthma through a combination of bioinformatics and in vivo experimental validation. We searched for active compounds in YPG and asthma targets from multiple databases and obtained common targets. Subsequently, a protein-protein interaction (PPI) network for compound disease was constructed using the protein interaction database for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, hematoxylin and eosin (H&E) staining, Masson staining, enzyme-linked immunosorbent assay (ELISA) analysis, immunofluorescence (IF) experiments, and Western blot (WB) experiments were performed to verify the possible mechanism of action of YPG for asthma treatment. Results: We obtained 72 active ingredients and 318 drug target genes that overlap with asthma. Serine/threonine-protein kinase (AKT1), tumor protein p53 (TP53), tumor necrosis factor (TNF), interleukin (IL)-6, IL-1ß, vascular endothelial growth factor-A (VEGFA), prostaglandin-endoperoxide synthase 2 (PTGS2), caspase-3 (CASP3), mitogen-activated protein kinase 3 (MAPK3) and epidermal growth factor receptor (EGFR) were the most relevant genes in the PPI network. KEGG analysis showed a high number of genes enriched for the nuclear factor kappa-B (NF-κB) signaling pathway. Animal experiments confirmed that YPG reduced inflammatory cell infiltration and down-regulated the expression of ovalbumin-induced inflammatory factors. Furthermore, YPG treatment decreased the protein expression of NFĸB1, nuclear factor kappa B kinase subunit beta (IKBKB), vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor 2 (VEGFR2) in lung tissue. Conclusion: YPG has a positive effect on asthma by interfering with multiple targets. Furthermore, YPG may significantly inhibit the follicle-induced inflammatory response through the NF-ĸB signaling pathway.

Consistency of P53 immunohistochemical expression between preoperative biopsy and final surgical specimens of endometrial cancer.

Objective: The aim of this study is to explore the consistency of P53 immunohistochemical expression between preoperative biopsy and final pathology in endometrial cancer (EC), and to predict the prognosis of patients based on the 4-tier P53 expression and classic clinicopathological parameters. Methods: The medical data of patients with stage I-III EC who received preoperative biopsy and initial surgical treatment in two medical centers was retrospectively collected. The consistency of P53 immunohistochemistry expression between preoperative biopsy and final pathology was compared using Cohen's kappa coefficient and Sankey diagram, then 4-tier P53 expression was defined (P53wt/P53wt, P53abn/P53wt, P53wt/P53abn, and P53abn/P53abn). Univariate and multivariate Cox regression analysis was used to determine the correlation between 4-tier P53 expression and the prognosis of patients. On this basis, the nomogram models were established to predict the prognosis of patients by combining 4-layer P53 expression and classic clinicopathological parameters, then risk stratification was performed on patients. Results: A total of 1186 patients were ultimately included in this study through inclusion and exclusion criteria. Overall, the consistency of P53 expression between preoperative biopsy and final pathology was 83.8%, with a kappa coefficient of 0.624. ROC curve suggested that the AUC of 4-tier P53 expression to predict the prognosis of patients was better than AUC of P53 expression in preoperative biopsy or final pathology alone. Univariate and multivariate Cox regression analysis suggested that 4-tier P53 expression was an independent influencing factor for recurrence and death. On this basis, the nomogram models based on 4-tier P53 expression and classical clinicopathological factors were successfully established. ROC curve suggested that the AUC (AUC for recurrence and death was 0.856 and 0.838, respectively) of the models was superior to the single 4-tier P53 expression or the single classical clinicopathological parameters, which could provide a better risk stratification for patients. Conclusion: The expression of P53 immunohistochemistry had relatively good consistency between preoperative biopsy and final pathology of EC. Due to the discrepancy of P53 immunohistochemistry between preoperative biopsy and final pathology, the prognosis of patients can be better evaluated based on the 4-layer P53 expression and classic clinical pathological parameters.

Establishment and validation of a nomogram model for predicting adverse pregnancy outcomes of pregnant women with adenomyosis.

PURPOSE: To establish a reliable nomogram model to predict the risk of major adverse pregnancy outcomes in pregnant women with adenomyosis, and to provide a reference tool for the hierarchical management and the prenatal examination of pregnant women. METHODS: We collected the clinical data of pregnant women with adenomyosis who were treated in the First Affiliated Hospital of Chongqing Medical University, the Women and Children's Hospital of Chongqing Medical University, and Yubei District People's Hospital of Chongqing from January 2014 to June 2020. They were divided into the training cohort and the validation cohort, respectively. In the training cohort, we screened out risk factors associated with major adverse pregnancy outcomes and established a model, which was subsequently validated. RESULTS: In the training cohort, we found that previous parity, natural conception or not, type of adenomyosis, with or without endometriosis, history of infertility or adverse pregnancy outcomes, and history of uterine body surgery were associated with major adverse pregnancy outcomes of pregnant women with adenomyosis, and based on these factors, a nomogram model was constructed. The calibration curves of the model were well fitted in both the training and validation cohorts. The receiver-operating characteristic curve (ROC curve) showed that the area under the curve (AUC) was 0.873 and 0.851 in the training and validation cohorts, respectively. The optimal risk threshold of the model was 0.22, and this threshold can be applied to risk stratification of pregnant women. CONCLUSION: The nomogram model established in this study can reliably predict the risk of major APO in pregnant women with AD.

Induction mechanism of ferroptosis: A novel therapeutic target in lung disease.

Ferroptosis is a newly discovered form of non-apoptotic regulatory cell death driven by iron-dependent lipid peroxidation. Ferroptosis significantly differs from other forms of cell death in terms of biochemistry, genetics, and morphology. Ferroptosis affects many metabolic processes in the body, resulting in disruption of homeostasis, and is related to many types of lung disease. Although current research on ferroptosis remains in the early stage, existing studies have confirmed that ferroptosis is regulated by a variety of genes, mainly involving changes in genes involved in iron homeostasis and lipid peroxidation metabolism. Furthermore, the mechanism of ferroptosis is complex. This review summarizes the confirmed mechanisms that can cause ferroptosis, including activation of glutathione peroxidase 4, synthesis of glutathione, accumulation of reactive oxygen species, and the influence of ferrous ions and p53 proteins. In recent years, the mechanism of ferroptosis in the occurrence and development of many diseases has been studied; the occurrence of ferroptosis will produce an inflammatory storm, and most of the inducing factors and pathological manifestations of lung diseases are also inflammatory reactions. Therefore, we believe that the association between ferroptosis and lung disease deserves further study. This article aims to help readers to better understand the mechanism of ferroptosis, provide new ideas and targets for the treatment of lung diseases, and point out the direction for the development of new targeted drugs for the clinical treatment of lung diseases.

Predicting the Recurrence of Operable Cervical Cancer Patients Based on Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score and Classical Clinicopathological Parameters.

Objective: The purpose of this study was to evaluate the prognostic value of hemoglobin, albumin, lymphocyte, and platelet (HALP) score in patients with operable cervical cancer, and on this basis, combined with classical clinicopathological parameters to predict the recurrence of patients. Methods: A total of 1580 patients with stage IA-IIA cervical cancer were randomly divided into training cohort (n=1054) and validation cohort (n=526) according to the predefined ratio of 2:1. In the training cohort, the receiver operating characteristic (ROC) curve and Youden index were used to determine the optimal threshold of HALP score for predicting cervical cancer recurrence. On this basis, the independent related factors with cervical cancer recurrence were screened through univariate and multivariate Cox regression analysis, and then a nomogram model was further established. The internal and external validation of the model was carried out in the training cohort and the validation cohort respectively through the consistency index (C-index) and calibration curve. Results: ROC curve and Youden index showed that the optimal threshold of HALP score for predicting cervical cancer recurrence was 39.50. Multivariate analysis confirmed that HALP score and some other classic clinicopathological parameters were independently associated with cervical cancer recurrence. Based on the results of multivariate analysis, a nomogram model for predicting cervical cancer recurrence was successfully constructed. The internal and external calibration curves showed that the fitting degree of the model was good, and the C-index (the C-index of the training cohort and the validation cohort were 0.862 and 0.847, respectively) showed that the prediction accuracy of the model proposed in this study was better than other similar models. Conclusion: HALP score may be a novel predictor for predicting the cervical cancer recurrence. Nomogram model based on HALP score and classical clinicopathological parameters can better predict the recurrence of cervical cancer.

Preoperative Neutrophil to Lymphocyte Ratio Predicts Complications After Esophageal Resection That can be Used as Inclusion Criteria for Enhanced Recovery After Surgery.

Background: The neutrophil to lymphocyte ratio (NLR) has been reported as an indicator for poor prognosis in many cancers including esophageal cancer. However, the relationship between the NLR and postoperative complications after esophageal cancer resection remains unclear. At present, enhanced recovery after surgery (ERAS) lacks inclusion criteria. The aim of this study is to determine whether the preoperative NLR (preNLR) can predict complications after esophageal cancer resection, which could represent the criteria for ERAS. Methods: This was a retrospective study on 171 patients who underwent esophagectomy at Hospital between November 2020 and November 2021(68 patients from Changhai Hospital, 65 patients from Shanghai General Hospital and 38 patients from Affiliated Hospital of Qingdao University). Univariate and multivariate logistic regression analyses were performed to demonstrate that the preNLR could predict complications after esophagectomy. Results: A preNLR cutoff value of 2.30 was identified as having the greatest ability to predict complications with a sensitivity of 76% and specificity of 65%. Moreover, the Chi-squared test results showed that the preNLR was significantly associated with complications (x2 = 13.641, p < 0.001), and multivariate logistic regression analysis showed that body mass index (BMI), p stage and preNLR were independent variables associated with the development of postoperative complications (p < 0.05). Conclusion: The preNLR can predict complications after esophagectomy, and these predicted complications can represent the criteria for recruiting patients for ERAS.

A Nomogram Model for Predicting Recurrence of Stage I-III Endometrial Cancer Based on Inflammation-Immunity-Nutrition Score (IINS) and Traditional Classical Predictors.

Objective: The purpose of this study was to investigate the prognostic value of the inflammation-immunity-nutrition score (IINS) in patients with stage I-III endometrial cancer (EC) and establish a nomogram model to predict the recurrence of EC by combining IINS and traditional classical predictors. Methods: Seven hundred and seventy-five patients with stage I-III EC who underwent initial surgical treatment at the First Affiliated Hospital of Chongqing Medical University were included in this study as the training cohort. In the training cohort, IINS (0-3) was constructed based on preoperative C-reactive protein (CRP), lymphocytes (LYM), and albumin (ALB). Univariate and multivariate Cox regression analysis were used to screen independent predictors associated with recurrence of EC for developing the nomogram model. Internal validation of the model was performed in the training cohort by using the C-index and calibration curve, while external validation of the model was performed in another cohort (validation cohort) of 491 patients from the Second Affiliated Hospital of Chongqing Medical University. Results: IINS was successfully constructed, and survival analysis showed that patients with high IINS had a worse prognosis. Multivariate analysis showed that IINS, age, FIGO stage, pathological type, myometrial invasion, lymphatic vessel space invasion (LVSI), Ki67 expression, estrogen receptor (ER) expression, and P53 expression were significantly associated with shorter recurrence-free survival, and then a nomogram model for predicting the recurrence of EC was successfully established. The internal and external calibration curves of the model showed that the model fit well, and the C-index (0.887 in training cohort and 0.883 in validation cohort) showed that the model proposed in this study had better prediction accuracy than other prediction models. Conclusion: IINS may be a strong predictor of prognosis in patients with EC. The nomogram model incorporated into the IINS can better predict the recurrence of EC than the traditional models.