Prognostic Value of Insulin Growth Factor-Like Receptor 1 (IGFLR1) in Stage II and III Colorectal Cancer and Its Association with Immune Cell Infiltration.

IGFLR1 is a novel biomarker, and some evidences suggested that is involved in the immune microenvironment of CRC. Here, we explored the expression of IGFLR1 and its association with the prognosis as well as immune cell infiltration in CRC, with the aim to provide a basis for further studies on IGFLR1. Immunohistochemical staining for IGFLR1, TIM-3, FOXP3, CD4, CD8, and PD-1 was performed in eligible tissues to analyze the expression of IGFLR1 and its association with prognosis and immune cell infiltration. Then, we screened colon cancer samples from TCGA and grouped patients according to IGFLR1-related genes. We also evaluated the co-expression and immune-related pathways of IGFLR1 to identify the potential mechanism of it in CRC. When P < 0.05, the results were considered statistically significant. IGFLR1 and IGFLR1-related genes were associated with the prognosis and immune cell infiltration (P < 0.05). In stage II and III CRC tissue and normal tissue, we found (1) IGFLR1 was expressed in both the cell membrane and cytoplasm and which was differentially expressed between cancer tissue and normal tissue. IGFLR1 expression was associated with the expression of FOXP3, CD8, and gender but was not associated with microsatellite instability. (2) IGFLR1 was an independent prognostic factor and patients with high IGFLR1 had a better prognosis. (3) A model including IGFLR1, FOXP3, PD-1, and CD4 showed good prognostic stratification ability. (4) There was a significant interaction between IGFLR1 and GATA3, and IGFLR1 had a significant co-expression with related factors in the INFR pathway. IGFLR1 has emerged as a new molecule related to disease prognosis and immune cell infiltration in CRC patients and showed a good ability to predict the prognosis of patients.

Characteristics of Inflammatory and Normal Endothelial Exosomes on Endothelial Function and the Development of Hypertension.

Endothelial dysfunction is associated with the development of hypertension. We hypothesize that inflammatory and normal endothelial exosomes play their roles by mediating endothelial function, and they induce endothelial angiogenesis through different signaling pathways. Endothelial cell-derived exosomes were isolated from the human umbilical vein endothelial cells (HUVECs) treated with (TExo) or without (CExo) tumor necrosis factor (TNF)-α. We monitored dermal microcirculation profiles in spontaneously hypertensive rats (SHRs) and WKY rats using a laser Doppler imager and a laser Doppler perfusion and temperature monitor. Tube formation, levels of angiogenesis-related proteins in HUVEC-conditioned media, and reactive oxygen species (ROS) levels were assessed following TNF-α, CExo, or TExo treatments. Western blot analysis was conducted to examine signaling proteins associated with inflammation and ROS. The results showed increased blood perfusion and the mean amplitude of endothelial oscillator in SHRs following CExo administration. TNF-α, CExo, and TExo treatments promoted endothelial tube formation and elevated levels of angiogenic factors and ROS. TExo significantly increased phosphorylation levels of STAT3, p38, and level of NF-κB, while decreasing phosphorylation levels of JNK and Erk (P < 0.01 or P < 0.05). CExo significantly increased STAT3 phosphorylation and reduced JNK and Erk phosphorylation (all P < 0.01). In conclusion, TNF-α and TExo induce inflammatory and pathological angiogenesis via the NF-κB pathway, while CExo exhibits a physiologically pro-angiogenic effect on endothelial cells. Increased ROS, interplaying with inflammatory signals, contribute to exosome-mediated alterations of endothelial function, thereby playing a role in the development of hypertension.

Trends in the prevalence and treatment of comorbid depression among US adults with and without cancer, 2005-2020.

BACKGROUND: Understanding trend characteristics of depression among cancer survivors is essential for healthcare policies and planning. This study estimates longitudinal trends in the prevalence and treatment of depression among adults in the United States with and without cancer. METHODS: This cross-sectional study focused on adults aged 20 years or older based on nationally representative data from the National Health and Nutrition Examination Surveys 2005-2020. Weighted logistic regression model was established to assess association between depression and cancer status after adjusting various covariates potentially related to depression. RESULTS: Among the 37,283 participants (weighted mean age, 47.5; women, 50.9 %), 3648 (9.8 %) were diagnosed with cancer and 3343 (9.0 %) were screened positive for depression. The age-standardized prevalence of depression showed a U-shaped trend in cancer survivors, decreasing from 11.8 % (95 % confidence interval, 8.4 %-15.2 %) in 2005-2008 to 8.3 % (5.6 %-11.0 %) in 2013-2016, then increasing to 11.7 % (6.3 %-17.2 %) in 2017-2020. These trends varied by population subgroup. Among depressive patients with cancer, antidepressant use increased from 38.6 % (28.7 %-48.5 %) in 2005-2008 to 62.9 % (40.6 %-85.2 %) in 2017-2020, whereas mental health consultation increased slightly. LIMITATIONS: Using a screening questionnaire instead of diagnostic criteria to identify depression; small sample size of patients with cancer; and cross-sectional analysis without prospective outcomes. CONCLUSIONS: From 2005 to 2020, the depression disease burden in patients with cancer eased in 2009-2015, but deteriorated recently. A healthy lifestyle and reasonable treatment for depression, based on an objective examination of depression characteristics, would improve long-term cancer outcomes and quality of life.

Prognosis of colon cancer patients based on enhancer RNAs-related genes.

PURPOSE: Colon cancer (CC) is a cancer of the large intestine with high prevalence and poor prognosis. enhancer RNAs. Therefore, valuable tools or biomarkers for predicting patient status, directing clinical practice, and reducing overtreatment are needed. Enhancer RNAs (eRNAs), a class of noncoding RNAs transcribed from enhancers, have been shown to function as regulators of oncogene or tumor suppressor gene expression. The aim of our study was to explore the potential roles of eRNAs and their target enhancer-related genes (ERGs) in the prognosis of CC. METHODS: Selected CC cases (stage I-III) from The Cancer Genome Atlas database were used as a training set, and cases from the Gene Expression Omnibus were used as the validation set. ERGs associated with prognosis were screened through three steps: potential, candidate, and prognosis ERGs. Multivariate Cox proportional hazards analysis was used to identify independent prognostic factors, and a nomogram was created. Calibration curves were drawn by comparing predicted and observed survival probability. For validation, the calibration curves and ROC analysis were also applied to two external validation sets. The biological significance and clinical application of the genes obtained were investigated. RESULTS: Based on the multiple tiers of strict screening, 11 prognostic ERGs were obtained, which were combined to obtain a prognosis signature. A compound nomogram integrating age, TNM classification, and the prognostic signature was constructed. The model was reliable in distinguishing the risk of patients with stage I-III CC, with AUCs of 0.78 and 0.70 at 5 and 7 years, respectively. There was good reproducibility in calibration curves. The prognostic model also yielded good prediction capability in the validation sets. CONCLUSION: In this study, the usefulness and specificity of the ERGs in prognosis were described, which should be considered a key feature in the clinical guidance of CC patients with early stage. We concluded that the major implications of the eRNAs and ERGs should be valued, which would be an emerging hallmark in the prognosis of cancer.

The significance of spread through air spaces in the prognostic assessment model of stage I lung adenocarcinoma and the exploration of its invasion mechanism.

PURPOSE: Spread through air spaces (STAS) is a crucial invasive mode of lung cancer and has been shown to be associated with early recurrence and metastasis. We aimed to develop a prognostic risk assessment model for stage I lung adenocarcinoma based on STAS and other pathological features and to explore the potential relationship between CXCL-8, Smad2, Snail, and STAS. METHODS: 312 patients who underwent surgery at Harbin Medical University Cancer Hospital with pathologically diagnosed stage I lung adenocarcinoma were reviewed in the study. STAS and other pathological features were identified by H&E staining, and a prognostic risk assessment model was established. The expression levels of CXCL8, Smad2, and Snail were determined by immunohistochemistry. RESULTS: The nomogram was established based on age, smoking history, STAS, tumor lymphocyte infiltration, tissue subtype, nuclear grade, and tumor size. The C-index for DFS was (training set 0.84 vs validation set 0.77) and for OS was (training set 0.83 vs validation set 0.78). Decision curve analysis showed that the model constructed has a better net benefit than traditional reporting. The prognostic risk score validated the risk stratification value for stage I lung adenocarcinoma. STAS was an important prognostic factor associated with stronger invasiveness and higher expression of CXCL8, Smad2, and Snail. CXCL8 was associated with poorer DFS and OS. CONCLUSIONS: We developed and validated a survival risk assessment model and the prognostic risk score formula for stage I lung adenocarcinoma. Additionally, we found that CXCL8 could be used as a potential biomarker for STAS and poor prognosis, and its mechanism may be related to EMT.

Efficacy of Yiqi Yangyin Jiedu decoction in postoperative patients with thyroid cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: There is no evidence-based data to confirm the efficacy of Yiqi Yangyin Jiedu Decoction (YYJD) in postoperative thyroid cancer patients. Therefore, in order to provide new evidence-based medical evidence for clinical treatment, we used this protocol to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of YYJD in postoperative patients with thyroid cancer. METHODS: This systematic review and meta-analysis has been prospectively registered in the PROSPERO (No. CRD42022365826). Six databases, including Medicine, Embase, Cochrane, CNKI, Wan Fang, and VIP, will be searched from their inception to February 1, 2023. Clinical controlled studies investigating the efficacy and safety of YYJD in patients after thyroid cancer surgery will all be considered for inclusion. The primary outcomes are tumor recurrence rate and overall survival. The secondary outcomes include treatment-related adverse effects, length of hospital stay, and patient satisfaction. All data will be analyzed using R version 3.4.3 to calculate pooled standardized mean differences for outcomes. Data that can not be retrieved will be interpreted from graphs using digital ruler software. RESULTS: The results of this paper will fill a gap in the literature regarding this project. CONCLUSION: We assume that the YYJD has a positive effect.

Brusatol sensitizes endometrial hyperplasia and cancer to progestin by suppressing NRF2-TET1-AKR1C1-mediated progestin metabolism.

Progestin resistance is the main obstacle for the conservative therapy to maintain fertility in women with endometrial cancer. Brusatol was identified as an inhibitor of the NRF2 pathway; however, its impact on progestin resistance and the underlying mechanism remains unclear. Here, we found that brusatol sensitized endometrial cancer to progestin by suppressing NRF2-TET1-AKR1C1-mediated progestin metabolism. Brusatol transcriptionally suppressed AKR1C1 via modifying the hydroxymethylation status in its promoter region through TET1 inhibition. Suppression of AKR1C1 by brusatol resulted in decreased progesterone catabolism and maintained potent progesterone to inhibit endometrial cancer growth. This inhibition pattern has also been found in the established xenograft mouse and organoid models. Aberrant overexpression of AKR1C1 was found in paired endometrial hyperplasia and cancer samples from the same individuals with progestin resistance, whereas attenuated or loss of AKR1C1 was observed in post-treatment samples with well progestin response as compared with paired pre-treatment tissues. Our findings suggest that AKR1C1 expression pattern may serve as an important biomarker of progestin resistance in endometrial cancer.

A Novel and Robust Prognostic Model for Hepatocellular Carcinoma Based on Enhancer RNAs-Regulated Genes.

Evidence has demonstrated that enhancer RNAs (eRNAs) play a vital role in the progression and prognosis of cancers, but few studies have focused on the prognostic ability of eRNA-regulated genes (eRGs) for hepatocellular carcinoma (HCC). Using gene expression profiles of HCC patients from the TCGA-LIHC and eRNA expression profiles from the enhancer RNA in cancers (eRic) data portal, we developed a novel and robust prognostic signature composed of 10 eRGs based on Lasso-penalized Cox regression analysis. According to the signature, HCC patients were stratified into high- and low-risk groups, which have been shown to have significant differences in tumor immune microenvironment, immune checkpoints, HLA-related genes, DNA damage repair-related genes, Gene-set variation analysis (GSVA), and the lower half-maximal inhibitory concentration (IC50) of Sorafenib. The prognostic nomogram combining the signature, age, and TNM stage had good predictive ability in the training set (TCGA-LIHC) with the concordance index (C-index) of 0.73 and the AUCs for 1-, 3-, and 5-year OS of 0.82, 0.77, 0.74, respectively. In external validation set (GSE14520), the nomogram also performed well with the C-index of 0.71 and the AUCs for 1-, 3-, and 5-year OS of 0.74, 0.77, 0.74, respectively. In addition, an important eRG (AKR1C3) was validated using two HCC cell lines (Huh7 and MHCC-LM3) in vitro, and the results demonstrated the overexpression of AKR1C3 is related to cell proliferation, migration, and invasion in HCC. Altogether, our eRGs signature and nomogram can predict prognosis accurately and conveniently, facilitate individualized treatment, and improve prognosis for HCC patients.

Assessing the depression risk in the U.S. adults using nomogram.

BACKGROUND: Depression has received a lot of attention as a common and serious illness. However, people are rarely aware of their current depression risk probabilities. We aimed to develop and validate a predictive model applicable to the risk of depression in US adults. METHODS: This study was conducted using the database of the National Health and Nutrition Examination Survey (NHANES, 2017-2012). In particular, NHANES (2007-2010) was used as the training cohort (n = 6015) for prediction model construction and NHANES (2011-2012) was used as the validation cohort (n = 2812) to test the model. Depression was assessed (defined as a binary variable) by the Patient Health Questionnaire (PHQ-9). Socio-demographic characteristics, sleep time, illicit drug use and anxious days were assessed using a self-report questionnaire. Logistic regression analysis was used to evaluate independent risk factors for depression. The nomogram has the advantage of being able to visualize complex statistical prediction models as risk estimates of individualized disease probabilities. Then, we developed two depression risk nomograms based on the results of logistic regression. Finally, several validation methods were used to evaluate the prediction performance of nomograms. RESULTS: The predictors of model 1 included gender, age, income, education, marital status, sleep time and illicit drug use, and model 2, furthermore, included anxious days. Both model 1 and model 2 showed good discrimination ability, with a bootstrap-corrected C index of 0.71 (95% CI, 0.69-0.73) and 0.85 (95% CI, 0.83-0.86), and an externally validated C index of 0.71 (95% CI, 0.68-0.74) and 0.83 (95% CI, 0.81-0.86), respectively, and had well-fitted calibration curves. The area under the receiver operating characteristic curve (AUC) values of the models with 1000 different weighted random sampling and depression scores of 10-17 threshold range were higher than 0.7 and 0.8, respectively. Calculated net reclassification improvement (NRI) and integrated discrimination improvement (IDI) showed the discrimination or accuracy of the prediction models. Decision curve analysis (DCA) demonstrated that the depression models were practically useful. The network calculators work for participants to make personalized predictions. CONCLUSIONS: This study presents two prediction models of depression, which can effectively and accurately predict the probability of depression as well as helping the U.S. civilian non-institutionalized population to make optimal treatment decisions.

Development and Validation of a Novel Prognostic Model for Lower-Grade Glioma Based on Enhancer RNA-Regulated Prognostic Genes.

Enhancer RNAs (eRNAs) are present specifically in tumors, where they affect the expression of eRNA-regulated genes (ERGs). Owing to this characteristic, ERGs were hypothesized to improve prognosis of overall survival in heterogeneous low-grade and intermediate-grade gliomas. This study aimed to construct and validate an ERG prognostic tool to facilitate clinical management, and offer more effective diagnostic and therapeutic biomarkers for glioma. Survival-related eRNAs were identified, and their ERGs were selected based on eRNA and target gene information. The ERG prognostic model was constructed and validated using internal and external validation cohorts. Finally, biological differences related to the ERG signature were analysed to explore the potential mechanisms influencing survival outcomes. Thirteen ERGs were identified and used to build an ERG risk signature, which included five super-enhancer RNA (seRNA)-regulated genes and five LGG-specific eRNA-regulated genes. The prognostic nomogram established based on combining the ERG score, age, and sex was evaluated by calibration curves, clinical utility, Harrell's concordance index (0.86; 95% CI: 0.83-0.90), and time-dependent receiver operator characteristic curves. We also explored potential immune-related mechanisms that might cause variation in survival. The established prognostic model displayed high validity and robustness. Several immune-related genes regulated by seRNAs or specific eRNAs were identified, indicating that these transcripts or their genes were potential targets for improving immunotherapeutic/therapeutic outcomes. The functions of an important specific eRNA-regulated gene (USP28) were validated in robust vitro experiments. In addition, the ERG risk signature was significantly associated with the immune microenvironment and other immune-related features.

Three-Dimensional Genome Interactions Identify Potential Adipocyte Metabolism-Associated Gene STON1 and Immune-Correlated Gene FSHR at the rs13405728 Locus in Polycystic Ovary Syndrome.

Background: rs13405728 was identified as one of the most prevalent susceptibility loci for polycystic ovary syndrome (PCOS) in Han Chinese and Caucasian women. However, the target genes and potential mechanisms of the rs13405728 locus remain to be determined. Methods: Three-dimensional (3D) genome interactions from the ovary tissue were characterized via high-through chromosome conformation capture (Hi-C) and Capture Hi-C technologies to identify putative targets at the rs13405728 locus. Combined analyses of eQTL, RNA-Seq, DNase-Seq, ChIP-Seq, and sing-cell sequencing were performed to explore the molecular roles of these target genes in PCOS. PCOS-like mice were applied to verify the expression patterns. Results: Generally, STON1 and FSHR were identified as potential targets of the rs13405728 locus in 3D genomic interactions with epigenomic regulatory peaks, with STON1 (P=0.0423) and FSHR (P=0.0013) being highly expressed in PCOS patients. STON1 co-expressed genes were associated with metabolic processes (P=0.0008) in adipocytes (P=0.0001), which was validated in the fat tissue (P<0.0001) and ovary (P=0.0035) from fat-diet mice. The immune system process (GO:0002376) was enriched in FSHR co-expressed genes (P=0.0002) and PCOS patients (P=0.0002), with CD4 high expression in PCOS patients (P=0.0316) and PCOS-like models (P=0.0079). Meanwhile, FSHR expression was positively correlated with CD4 expression in PCOS patients (P=0.0252) and PCOS-like models (P=0.0178). Furthermore, androgen receptor (AR) was identified as the common transcription factor for STON1 and FSHR and positively correlated with the expression of STON1 (P=0.039) and FSHR (P=4e-06) in ovary tissues and PCOS-like mice. Conclusion: Overall, we identified STON1 and FSHR as potential targets for the rs13405728 locus and their roles in the processes of adipocyte metabolism and CD4 immune expression in PCOS, which provides 3D genomic insight into the pathogenesis of PCOS.

LRP1B mutation is associated with tumor HPV status and promotes poor disease outcomes with a higher mutation count in HPV-related cervical carcinoma and head & neck squamous cell carcinoma.

Human papillomavirus (HPV) infection and gene mutations were reputed as key factors in cervical carcinoma (CC) and head and neck squamous cell carcinoma (HNSCC). However, the associations of HPV status and gene mutations remain to be determined. This study aims to identify molecular patterns of LRP1B mutation and HPV status via rewiring tumor samples of HNSCC (n=1478) and CC (n=178) from the TCGA dataset. Here, we found that LRP1B mutation was associated with HPV status in CC (P=0.040) and HNSCC (P=0.044), especially in HPV 16 integrated CC (P=0.036). Cancer survival analysis demonstrated that samples with LRP1B mutation showed poor disease outcomes in CC (P=0.013) and HNSCC (P=0.0124). In addition, the expression status of LPR1B was more favorable for prediction than TP53 or RB1 in CC and HNSCC. Mutation clustering analysis showed that samples with LRP1B mutation showed higher mutation count in CC (P=1.76e-67) and HNSCC (P<10e-10). Further analysis identified 289 co-occurrence genes in these two cancer types, which were enriched in PI3K signaling, cell division process, and chromosome segregation process, et al. The 289-co-occurrence gene signature identified a cluster of patients with a higher portion of copy number variation (CNV) lost in the genome, different tumor HPV status (P<10e-10), higher mutation count (P<10e-10), higher fraction genome altered value (P=2.078e-4), higher aneuploidy score (P=3.362e-4), and earlier started the smoking year (P=2.572e-4), which were associated with shorter overall survival (P=0.0103) in CC and HNSCC samples. Overall, LRP1B mutation was associated with tumor HPV status and was an unfavorable prognostic biomarker for CC and HNSCC.

A Novel Prognostic Tool for Glioma Based on Enhancer RNA-Regulated Immune Genes.

Background: Gliomas are the most malignant tumors of the nervous system. Even though their survival outcome is closely affected by immune-related genes (IRGs) in the tumor microenvironment (TME), the corresponding regulatory mechanism remains poorly characterized. Methods: Specific enhancer RNAs (eRNAs) can be found in tumors, where they control downstream genes. The present study aimed to identify eRNA-regulated IRGs, evaluate their influence on the TME, and use them to construct a novel prognostic model for gliomas. Results: Thirteen target genes (ADCYAP1R1, BMP2, BMPR1A, CD4, DDX17, ELN, FGF13, MAPT, PDIA2, PSMB8, PTPN6, SEMA6C, and SSTR5) were identified and integrated into a comprehensive risk signature, which distinguished two risk subclasses. Discrepancies between these subclasses were compared to explore potential mechanisms attributed to eRNA-regulated genes, including immune cell infiltration, clinicopathological features, survival outcomes, and chemotherapeutic drug sensitivity. Furthermore, the risk signature was used to construct a prognostic tool that was evaluated by calibration curve, clinical utility, Harrell's concordance index (0.87; 95% CI: 0.84-0.90), and time-dependent receiver operator characteristic curves (AUCs: 0.93 and 0.89 at 3 and 5 years, respectively). The strong reliability and robustness of the established prognostic tool were validated in another independent cohort. Finally, potential subtypes were explored in patients with grade III tumors. Conclusion: Overall, eRNAs were associated with immune-related dysfunctions in the TME. Targeting of IRGs regulated by eRNAs could improve immunotherapeutic/therapeutic outcomes.

Construction of a disease-specific lncRNA-miRNA-mRNA regulatory network reveals potential regulatory axes and prognostic biomarkers for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with a high incidence and poor prognosis. Exploration of the underlying mechanisms and effective prognostic indicators is conducive to clinical management and optimization of treatment. The RNA-seq and clinical phenotype data of HCC were retrieved from The Cancer Genome Atlas (TCGA), and differential expression analysis was performed. Then, a differential lncRNA-miRNA-mRNA regulatory network was constructed, and the key genes were further identified and validated. By integrating this network with the online tool-based ceRNA network, an HCC-specific ceRNA network was obtained, and lncRNA-miRNA-mRNA regulatory axes were extracted. RNAs associated with prognosis were further obtained, and multivariate Cox regression models were established to identify the prognostic signature and nomogram. As a result, 198 DElncRNAs, 120 DEmiRNAs, and 2827 DEmRNAs were identified, and 30 key genes identified from the differential network were enriched in four cancer-related pathways. Four HCC-specific lncRNA-miRNA-mRNA regulatory axes were extracted, and SNHG11, CRNDE, MYLK-AS1, E2F3, and CHEK1 were found to be related with HCC prognosis. Multivariate Cox regression analysis identified a prognostic signature, comprised of CRNDE, MYLK-AS1, and CHEK1, for overall survival (OS) of HCC. A nomogram comprising the prognostic signature and pathological stage was established and showed some net clinical benefits. The AUC of the prognostic signature and nomogram for 1-year, 3-year, and 5-year survival was 0.777 (0.657-0.865), 0.722 (0.640-0.848), and 0.630 (0.528-0.823), and 0.751 (0.664-0.870), 0.773 (0.707-0.849), and 0.734 (0.638-0.845), respectively. These results provided clues for the study of potential biomarkers and therapeutic targets for HCC. In addition, the obtained 30 key genes and 4 regulatory axes might also help elucidate the underlying mechanism of HCC.

[Wenweishu Capsule alleviates gastric mucosal lesion in rats with chronic gastritis by inhibiting NF-κB pathway].

Objective To investigate the effect of Wenweishu Capsule on the expression of nuclear factor kappa B (NF-κB)-related proteins in chronic gastritis model rats. Methods Wistar rat models of chronic gastritis were constructed by alternant administrations of sodium deoxycholate, ammonia, alcohol solution and the hunger disorder method. The rats were randomly divided into control group, model group, vatacoenayme group, high-, middle- and low-dose Wenweishu Capsule groups. The control group and model group were treated with normal saline (2 mL/d). The other groups were separately treated with 0.3 g/kg vatacoenayme and 0.76, 0.38, 0.19 g/kg Wenweishu Capsule for 4 weeks. Naked eye observation and HE staining were used to evaluate the pathological changes of gastric tissue. ELISA was performed to measure the levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in the serum. Immunofluorescence staining was employed to observe the expression of NF-κBp65, inhibitor of NF-κBα (IκBα) in the gastric tissue. Simple Western was utilized to detect the protein levels of NF-κBp65, IκBα and COX2 in the gastric tissue. Results Compared with the control group, the model group was found with thinner gastric mucosa, disappeared or shallower folds, obviously infiltrated mucosa inflammatory cells, disordered glands, and significantly increased levels of serum inflammatory cytokines and NF-κBp65, IκBα and COX2 proteins in the gastric tissue. Compared with the model group, the vatacoenayme group, high- and middle-dose Wenweishu Capsule groups showed the alleviated gastric cavity signs, improved histopathological changes, reduced levels of TNF-α and IL-6 in the serum, and decreased expression of NF-κBp65, IκBα and COX2 proteins in the gastric tissue. Conclusion Wenweishu Capsule can reduce the levels of serum inflammatory factors by inhibiting NF-κB pathway in the gastric tissue, so as to alleviate the injury of gastric mucosa in rats with chronic gastritis.

Fast-stimulating bioremediation of macro crude oil in soils using matching Fenton pre-oxidation.

This study aims at exploring the mechanism of fast-stimulating bioremediation of macro crude oil using matching Fenton pre-oxidation. The 80-day biodegradation experiment for soil S1 and S2, containing macro crude oil: C19-C29 and C17-C29 respectively, was conducted after Fenton pre-oxidation with three concentrations of H2O2 (225 mM, 450 mM, and 900 mM). Experimental results indicated that the bioremediation efficiency of macro crude oil was up to 57.1% (8853 mg/kg, S1) and 64.4% (11,719 mg/kg, S2) for 80-day fast-stimulating bioremediation using matching Fenton pre-oxidation (450 mM H2O2), which was 1.8-2.6 times that (S1: 22.2-37.1%; S2: 36.1-39.6%) for slow-stimulating bioremediation using un-matching Fenton pre-oxidation. Furthermore, the high-throughput analysis revealed that genera Sedimentibacter, Caenispirillum, and Brevundimonas became the dominant bacteria after matching Fenton pre-oxidation. Meanwhile, the highest logarithmic growth rate of indigenous hydrocarbon degraders (IHD) was obtained (S1: 64% and S2: 60%) for fast-stimulating bioremediation. And the consumption of NH4+-N was up to 90% and 94% in S1 and S2 within 60 days for fast-stimulating bioremediation, approximately 1.4 and 2.2 times that (S1: 65% and 62%; S2: 47% and 41%) for slow-stimulating remediation. The results showed that the macro crude oil became the main carbon source for IHD for the fast-stimulating bioremediation, resulting in the rapid growth of IHD. Thus, this study provides a fast and efficient remediation technology for bioremediation of macro crude oil-contaminated soils.

[Improving Bioremediation of Crude Oil-contaminated Soil by Mild Pre-oxidation].

To obtain a mild Fenton pre-oxidation method, which could promote the efficient degradation of total petroleum hydrocarbons (TPH) in subsequent bioremediation, the differences in the characteristics of the hydroxyl radical (·OH), nutrient consumption, activity of indigenous bacteria (CO2), and TPH removal were investigated during subsequent bioremediation after different Fenton pre-oxidation treatments. The results showed that high biodegradation of TPH was observed after mild Fenton pre-oxidation (·OH existence time:73 h; H2O2 concentration:225 mmol·L-1), because of the high activity of residual bacteria. Moreover, the same TPH removal with the addition of bacteria could be achieved without adding bacteria (the TPH removal rate 38%) because the activity of the residual bacteria was strong after mild Fenton pre-oxidation. Under the condition of no additional bacteria source, mild Fenton pre-oxidation TPH removal (approximately 38%) was higher than that after ordinary Fenton pre-oxidation (15.32%-33.15%). Further analysis of the removal efficiency of each chain of hydrocarbons revealed that the mild pre-oxidation group could reduce the inhibition of the chain hydrocarbon components (C17-C21) in the subsequent bioremediation stage. Comparing the activity of the indigenous bacteria in each group, revealed that mild pre-oxidation could appropriately stimulate the growth and increase the activity of indigenous microorganisms, all of which are beneficial to the removal of TPH.

The effect of salpingectomy on the ovarian reserve and ovarian response in ectopic pregnancy: A systematic review and meta-analysis.

BACKGROUND: Salpingectomy is routinely performed in ectopic pregnancy (EP). However, the effect of the surgery on the ovarian reserve and ovarian response in EP patients is still uncertain and has not been systematically evaluated. Therefore, we conducted this meta-analysis to provide a comparison of the ovarian reserve and ovarian response between the pre-salpingectomy and post-salpingectomy in EP patients. METHODS: Pubmed, Embase, and Cochrane Library were searched for all relevant articles published up to December 2018. We retrieved the basic information and data of the included studies. The data was analyzed by Review Manager 5.3 software (Cochrane Collaboration, Oxford, UK). RESULTS: A total of 243 articles were extracted from the databases, and 7 studies were included in the meta-analysis. The ovarian reserve including anti-Mullerian hormone (inverse variance [IV] -0.7 [95% confidence interval [CI] -0.63, 0.49]), antral follicle count (IV 1.7 [95% CI -2.02, 5.42]) and basal follicle stimulating hormone (IV 0.02 [95% CI -0.63, 0.68]) was comparable between the pre-salpingectomy group and the post-salpingectomy group. The amount of gonadotropin was significantly higher in the post-salpingectomy group when compared with that in the pre-salpingectomy group (IV -212.65 [95% CI -383.59, -41.71]). There was no significant difference in the left parameters of the ovarian response including the duration of gonadotropin stimulation (IV -0.32 [95% CI -0.76, 0.12]), the estrogen level on the human chorionic gonadotropin triggering day (IV -4.12 [95% CI -236.27, -228.04]) and the number of retrieved oocytes (IV 0.35 [95% CI -0.76, 1.46]) between 2 groups. CONCLUSIONS: The current results suggest that salpingectomy has no negative effect on the ovarian reserve and ovarian response.

Rapid degradation of long-chain crude oil in soil by indigenous bacteria using fermented food waste supernatant.

The objective of this study is to explore how to stimulate soil indigenous bacteria for the degradation of long-chain crude oil by adding fermented food waste supernatant (FS). Four concentrations of FS (0 mL, 0.1 mL, 1 mL, and 3 mL) were added to two oil-contaminated soils S1 and S2 for 30 days of bioremediation experiments. The results showed that the biodegradation of long-chain alkanes (C29 - C24) could reach up to 1756 mg/kg (49.3%, S1) and 3937 mg/kg (43.9%, S2), which were 3.1 and 3.2 times that of the non-nutrient system. In addition, the logarithmic growth rate of the indigenous hydrocarbon degraders (IHD) reached 41.5%. The long-chain crude oil can be rapidly degraded by indigenous bacteria with FS added in a short time. The glucose and acetic acid accelerated the consumption of ammonia nitrogen (NH4+-N) in the prophase of bioremediation and the molar ratio of consumed carbon (contained in glucose and acetic acid) to consumed NH4+-N (C/N) was high by adding FS. Thus, the IHD can multiply rapidly. The analysis of microbial diversity revealed that the IHD (genera Acinetobacter and Aquabacterium) became the dominant bacteria. Long-chain alkanes became the main carbon sources for IHD after 14 days in soil S1 and 16 days in soil S2. Thus, the rapid biodegradation of long-chain crude oil was achieved. The genus Aquabacterium which was uncultivable on crude oil medium became the dominant bacteria. This study provides an environment-friendly and sustainable remediation technology for bioremediation of oil-contaminated soils.

Effects of tumor necrosis factor-α-induced exosomes on the endothelial cellular behavior, metabolism and bioenergetics.

OBJECTIVE: To investigate the effects of TNF-α-induced exosomes release on the biological behavior, metabolism, and bioenergetics of HUVECs. METHODS: Exosomes were isolated from conditioned media of HUVECs by ultracentrifugation after treatment with or without TNF-α. HUVECs were treated with or without TNF-α, or different concentrations of exosomes isolated from conditioned media with or without TNF-α induction (TExo and CExo , respectively). RESULTS: The results showed that TNF-α significantly inhibited migration, tube formation, and increased apoptosis rate of HUVECs compared with controls. Furthermore, TNF-α-induced exosomes (TExo ) rather than CExo , indicated similar effects to inhibit migration, tube formation and promote endothelial apoptosis. Although TNF-α treatment did not show a statistical difference, TExo significantly inhibited extracellular OCR compared with controls. TExo could significantly inhibited intracellular OCR in a hypoxia condition. TNF-α significantly increased L-ECA compared with control cells, and TExo showed similar stimulative effect on L-ECA. CONCLUSIONS: TNF-α-induced exosomes could significantly (a) change migration, tube formation, and apoptosis; (b) inhibit endothelial extracellular OCR and intracellular OCR (hypoxia); (c) increase glycolysis rate of the endothelial cells. These data provide new evidence for exploring endothelial behavior regulation using exosomes and their effects on endothelial metabolism and bioenergetics.