Occult Breast Cancer Presenting as Sternum Pain.

Bone metastasis has been reported in up to 70% of patients with advanced breast cancer. A total of 55.76% of skeletal metastases in women were derived from breast cancer. However, patients with bone metastasis from an occult primary breast cancer are a rare subset of patients. Here, we present the case of a 38-year-old woman who had sternum pain for 4 months. A whole-body PET-CT scan revealed that the FDG uptake of both the sternum and internal mammary node was significantly increased. The final diagnosis of occult breast cancer was established by immunohistochemical (IHC) staining, which is of great significance for identifying the origin of a metastatic tumor despite no visualized lesions of mammary glands.

Molecular insights into gastric cancer: The impact of TGFBR2 and hsa-mir-107 revealed by microarray sequencing and bioinformatics.

BACKGROUND: Gastric carcinoma (GC) remains a significant therapeutic challenge, garnering widespread attention. Oxymatrine (OMT), an active component of the traditional Chinese medicine compound Kushen injection (CKI), has shown promising results in combination with chemotherapy for the treatment of GC. However, the molecular mechanisms underlying OMT's therapeutic effects in GC have yet to be elucidated. METHODS: The transcriptomic expression data of HGC-27 post-OMT intervention were obtained through microarray sequencing, while the miRNA and mRNA sequencing data for GC patients were sourced from the TCGA database. The mechanism of OMT intervention in GC is analyzed in multiple aspects, including Protein-Protein Interactions (PPI), Competitive Endogenous RNA (ceRNA) networks, correlation and co-expression analyses, immune infiltration, and clinical implications. RESULTS: By analyzing key modules, five critical mRNAs were identified, and their interacting miRNAs were predicted to construct a ceRNA network. Among these, TGFBR2 and hsa-miR-107 have correlations or co-expression relationships with other genes in the network. They are differentially expressed in most other cancers, associated with prognosis, and have diagnostic value. TGFBR2 also exhibits immune infiltration phenomena, and its high expression is linked to poor patient prognosis. Low expression of hsa-miR-107 is associated with poor patient prognosis. OMT may act on the TGFß/Smad signaling pathway or negatively regulate the WNT signaling pathway through the hsa-miR-107/BTRC axis, thereby inhibiting the onset and progression of GC. CONCLUSION: The mechanisms of OMT intervention in GC are diverse, TGFBR2 and hsa-miR-107 may serve as prognostic molecular biomarkers or potential therapeutic targets.

An emerging biomarker for the diagnosis and treatment of esophageal squamous cell carcinoma - Aurora A.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prominent form of esophageal cancer. Aurora A (AURKA), an enzyme that phosphorylates serine and threonine, has a vital function in controlling the process of separating chromosomes during cell division. The contribution of this entity has been documented in the advancement of malignant proliferations, including tumors occurring in the breast, stomach, and ovaries. METHODS: The potential molecular mechanism of AURKA is comprehensively examined through the analysis of bulk RNA-seq and single-cell RNA-seq data obtained from publicly available databases. This analysis encompasses various aspects such as expression levels, prognosis, and functional pathways, among others. RESULTS: The upregulation of AURKA in ESCC has been found to be correlated with the overall survival of patients. The functional annotation and pathway enrichment analysis conducted in this study lead to the conclusion that AURKA participates in the regulation of a number of malignant processes connected to cell proliferation, such as cell cycle control, apoptosis, and the p53 signaling pathway. Additionally, AURKA has been found to be associated with drug sensitivity and has an impact on the infiltration of tumor-infiltrating immune cells in ESCC. CONCLUSIONS: AURKA exhibits potential as a prognostic and therapeutic biomarker linked to the regulation of cell cycle and cell proliferation.

Systematic review and meta-analysis on the efficacy and safety of Injectable Lentinan combined with chemotherapy in the treatment of gastric cancer.

BACKGROUND: This study employed a meta-analysis to evaluate the efficacy and safety of adjunctive treatment with injectable Lentinan (LNT) in combination with chemotherapy for gastric cancer (GC). METHODS: Computer-based searches of 6 databases were performed to identify randomized controlled trials (RCTs) relevant to the treatment of GC with LNT through mid-March 2023. Two independent researchers performed risk of bias assessment and trial sequential analysis(TSA), extracted the data and used Revman 5.3 software for data analysis. The certainty of evidence was graded based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RESULTS: A total of 31 RCTs with 2729 patients were included in the analysis. The results revealed that adjunctive therapy with LNT was associated with improved treatment efficacy (RR = 1.48, 95%CI: 1.36 ∼ 1.61, p < 0.00001), improvement in clusters of differentiation (CD3+, CD4+, and CD4+/CD8+), natural killer (NK) cells, and quality of life assessment (RR = 1.32, 95%CI: 1.20 ∼ 1.45, p < 0.00001) compared to using chemotherapy alone. In addition, there was a reduction in CD8+ levels, incidence of white blood cell decline, gastrointestinal reactions, and platelet decline. TSA results indicated that there was sufficient evidence to draw firm conclusions about these outcomes, and the GRADE scores showed 'high' or 'moderate' quality of evidence for these outcomes. CONCLUSION: The efficacy of treatment of GC with LNT in combination with chemotherapy was found to be better than chemotherapy alone. And no serious adverse effects were observed. However, further RCTs are needed to further validate the results of this study.

A new strategy to identify ADAM12 and PDGFRB as a novel prognostic biomarker for matrine regulates gastric cancer via high throughput chip mining and computational verification.

BACKGROUND: Gastric cancer is a life-threatening disease that poses a serious risk to human health. Although there are numerous molecular targets for gastric cancer in clinical practice, they often exhibit low specificity and sensitivity. Consequently, this can result in a low early diagnosis rate, delayed treatment, and poor prognosis for patients with gastric cancer. Hence, it remains crucial to identify more precise diagnostic markers for this disease. METHODS: This study utilized ceRNA chips and bioinformatics methods to investigate the key genes and mechanisms involved in matrine intervention in gastric cancer cells. RESULTS: ADAM12 and PDGFRB are the key genes that are down-regulated after matrine intervention in gastric cancer cells. By conducting bioinformatics analysis, two ceRNA regulatory axes were identified, which are associated with the prognosis of gastric cancer. These axes are lncRNA DGCR5/hsa-miR-206/ADAM12 and circRNA ITGA3/hsa-miR-24-3p/PDGFRB. CONCLUSION: The low expression of ADAM12 may weaken the digestion of extracellular matrix (ECM) molecules, which can result in the invasion and metastasis of tumor cells. This occurs without the catalysis of ECM proteases, thereby impacting the invasion and metastasis of gastric cancer cells. Additionally, the analysis of immune infiltration suggests that ADAM12 and PDGFRB may influence changes in the tumor immune microenvironment, thereby affecting the occurrence and development of gastric cancer. This study contributes to a deeper understanding of the role of the matrine-related ceRNA network in gastric cancer, providing a reference for clinical diagnosis and treatment. It holds significant importance in discovering new drug treatment targets.

Identification of a disulfidptosis-related genes signature for prognostic implication in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer. Additionally, disulfidptosis, a newly discovered type of cell death, has been found to be closely associated with the onset and progression of tumors. METHODS: The study first identified genes related to disulfidptosis through correlation analysis. These genes were then screened using univariate cox regression and LASSO regression, and a prognostic model was constructed through multivariate cox regression. A nomogram was also created to predict the prognosis of LUAD. The model was validated in three independent data sets: GSE72094, GSE31210, and GSE37745. Next, patients were grouped based on their median risk score, and differentially expressed genes between the two groups were analyzed. Enrichment analysis, immune infiltration analysis, and drug sensitivity evaluation were also conducted. RESULTS: In this study, we examined 21 genes related to disulfidptosis and developed a gene signature that was found to be associated with a poorer prognosis in LUAD. Our model was validated using three independent datasets and showed AUC values greater than 0.5 at 1, 3, and 5 years. Enrichment analysis revealed that the disulfidptosis-related genes signature had a multifaceted impact on LUAD, particularly in relation to tumor development, proliferation, and metastasis. Patients in the high-risk group exhibited higher tumor purity and lower stromal score, ESTIMATE score, and Immune score. CONCLUSION: This study constructed a gene signature related to disulfidptosis in lung adenocarcinoma and analyzed its impact on the disease and its association with the tumor microenvironment. The findings of this research provide valuable insights into the understanding of lung adenocarcinoma and could potentially lead to the development of new treatment strategies.

Integrated network pharmacology analysis and in vitro validation revealed the underlying mechanism of Xiyanping injection in treating coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, leading to a pandemic. In China, Xiyanping injection (XYP) has been recommended as a drug for COVID-19 treatment in the Guideline on Diagnosis and Treatment of COVID-19 by the National Health Commission of the People Republic of China and National Administration of Traditional Chinese Medicine (Trial eighth Edition). However, the relevant mechanisms at the molecular-level need to be further elucidated. METHODS: In this study, XYP related active ingredients, potential targets and COVID-19 related genes were searched in public databases. Protein-protein interaction network and module analyzes were used to screen for key targets. gene ontology and Kyoto encyclopedia of genes and genomes were performed to investigate the potentially relevant signaling pathways. Molecular docking was performed using Autodock Tools and Vina. For the validation of potential mechanism, PolyI:C was used to induce human lung epithelial cells for an inflammation model. Subsequently, CCK-8 assays, enzyme-linked immunosorbent assay, reverse transcription quantitative polymerase chain reaction and western blot were employed to determine the effect of XYP on the expression of key genes. RESULTS: Seven effective active ingredients in XYP were searched for 123 targets in the relevant databases. Furthermore, 6446 COVID-19 disease targets were identified. Sodium 9-dehydro-17-hydro-andrographolide-19-yl sulfate was identified as the vital active compounds, and IL-6, TNF, IL-1ß, CXCL8, STAT3, MAPK1, MAPK14, and MAPK8 were considered as the key targets. In addition, molecular docking revealed that the active compound and the targets showed good binding affinities. The enrichment analysis predicted that the XYP could regulate the IL-17, Toll-like receptor, PI3K-Akt and JAK-STAT signaling pathways. Consistently, further in vitro experiments demonstrated that XYP could slow down the cytokine storm in the lung tissue of COVID-19 patients by down-regulating IL-6, TNF-α, IL-1ß, CXCL8, and p-STAT3. CONCLUSION: Through effective network pharmacology analysis and molecular docking, this study suggests that XYP contains many effective compounds that may target COVID-19 related signaling pathways. Moreover, the in vitro experiment confirmed that XYP could inhibit the cytokine storm by regulating genes or proteins related to immune and inflammatory responses.

Enhanced In Vitro Anti-Photoaging Effect of Degraded Seaweed Polysaccharides by UV/H2O2 Treatment.

The high molecular weight and poor solubility of seaweed polysaccharides have limited their function and application. In this study, ultraviolet/hydrogen peroxide (UV/H2O2) treatment was used to prepare low-molecular-weight seaweed polysaccharides from Sargassum fusiforme. The effects of UV/H2O2 treatment on the physicochemical properties and anti-photoaging activity of S. fusiforme polysaccharides were studied. UV/H2O2 treatment effectively degraded polysaccharides from S. fusiforme (DSFPs), reducing their molecular weight from 271 kDa to 26 kDa after 2 h treatment. The treatment did not affect the functional groups in DSFPs but changed their molar percentage of monosaccharide composition and morphology. The effects of the treatment on the anti-photoaging function of S. fusiforme polysaccharides were investigated using human epidermal HaCaT cells in vitro. DFSPs significantly improved the cell viability and hydroxyproline secretion of UVB-irradiated HaCaT cells. In particular, DSFP-45 obtained from UV/H2O2 treatment for 45 min showed the best anti-photoaging effect. Moreover, DSFP-45 significantly increased the content and expression of collagen I and decreased those of pro-inflammatory cytokines, including interleukin-1ß, interleukin-6, and tumor necrosis factor-α. Thus, UV/H2O2 treatment could effectively improve the anti-photoaging activity of S. fusiforme polysaccharides. These results provide some insights for developing novel and efficient anti-photoaging drugs or functional foods from seaweed polysaccharides.

Single-cell RNA sequencing integrated with bulk RNA sequencing analysis reveals diagnostic and prognostic signatures and immunoinfiltration in gastric cancer.

BACKGROUND: Early diagnosis and prognostic predication of gastric cancer (GC) pose significant challenges in current clinical practice of GC treatments. Therefore, our aim was to explore relevant gene signatures that can predict the prognosis of GC patients. METHODS: Here, we established a single-cell transcriptional atlas of GC, focusing on the expression of T-cell-related genes for cell-cell communication analysis, trajectory analysis, and transcription factor regulatory network analysis. Additionally, we conducted validation and prediction of immune-related prognostic gene signatures in GC patients using TCGA and GEO data. Based on these prognostic gene signatures, we predicted the immune infiltration status of GC patients by grouping the patient samples into high or low-risk groups. RESULTS: Based on 10 tumor samples and corresponding normal samples from GC patients, we selected 18,416 cells for subsequent analysis using single-cell sequencing. From these, we identified 3,284 T-cells and obtained 641 differentially expressed genes related to T-cells from 5 different T-cell subtypes. By integrating bulk RNA sequencing data, we identified prognostic signatures associated with T-cells. Stratifying patients based on these prognostic signatures into high-risk or low-risk groups allowed us to effectively predict their survival rates and the immunoinfiltration status of the tumor microenvironment. CONCLUSION: This study explored prognostic gene signatures associated with T-cells in GC patients, providing insights into predicting patients' survival rates and immunoinfiltration levels.

Study on the mechanism of Shujin Tongluo granules in treating cervical spondylosis based on network pharmacology and molecular docking.

BACKGROUND: To investigate the potential active ingredients and possible mechanisms of Shujin Tongluo granules (SJTLG) in the treatment of cervical spondylosis (CS) by network pharmacology and molecular docking. METHODS: The active ingredients and potential targets of SJTLG were obtained through databases such as traditional Chinese medicine system (TCMSP) and BATMAN-traditional Chinese medicine (TCM), and the relevant human targets of CS were identified through databases such as OMIM, GeneCards, and DisGeNET. The intersection targets were imported into STRING for protein-protein interaction (PPI) analysis. The obtained data were imported into Cytoscape 3.9.0 software for visualization, and module analysis was performed using the MCODE plug-in. The representative targets were screened through the Metascape website for pathway enrichment analysis in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Cytoscape software was used to build networks such as "drug-compound-target" and "drug-compound-target-pathway." Finally, the key targets were selected for molecular docking with the corresponding compounds by Autodock Tools 1.5.7 and visualized by PyMol. RESULTS: A total of 132 active compounds and 996 targets from SJTLG and 678 targets from CS were screened with 116 intersection targets. The key targets were AKT1, GAPDH, ALB, IL-6, TP53, TNF, VEGFA, IL-1ß, EGFR, HSP90AA1, ESR1, and JUN. The results of GO and KEGG enrichment analysis showed that the treatment of CS was mainly related to biological processes such as cellular response to nitrogen compound, cellular response to organonitrogen compound, and positive regulation of locomotion, and the targets were mainly focused on pathways in cancer, Kaposi sarcoma-associated herpesvirus infection, PI3K-Akt signaling pathway, lipid, and atherosclerosis. Molecular docking results showed that the minimum binding energy between the core targets and the corresponding compound was <-5.0 kcal·mol-1. CONCLUSION: This study preliminarily elucidates the potential active ingredients and mechanism of anti-inflammatory, analgesic, microcirculation improvement, vasodilation, osteoporosis inhibition and nerve nutrition effects of SJTLG in the treatment of CS and provides a reference for its clinical application.

Integrated analysis of single-cell RNA-seq and bulk RNA-seq unravels T cell-related prognostic risk model and tumor immune microenvironment modulation in triple-negative breast cancer.

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive and fatal malignancy. The current success of tumor immunotherapy has focused attention on intermediate T-cell subsets and the tumor microenvironment, which are essential for activation of the anti-tumor response. Therefore, both areas require further research to accelerate progress in developing tailored immunotherapeutic approaches for patients with TNBC. METHODS: We obtained scRNA-seq data of TNBC from the GEO database. A multiplex strategy was used to analyze and identify the T-cell heterogeneity of TNBC. By combining the METABRIC and GEO databases, a prognostic risk model for T-cell marker genes was constructed and validated. In addition, the immune-infiltrating cells of TNBC was analyzed using CIBERSORT, and the association between the risk model and response to immunotherapy was investigated. RESULTS: Based on scRNA-seq data, 25,932 cells were identified for multiple analyzes. T cells were studied with a focus on 2 subtypes, including CD8+ and CD4+. There were also communication relationships between T cells and multiple cell types. The results of the enrichment analysis showed that the T-cell marker genes were focused in pathways related to the immune system. In addition, OPTN, TMEM176A, PKM and HES1 deserve attention as prognostic markers in TNBC. The immune infiltration results showed that the high-risk group had significant immune cell infiltration and immunosuppression status. CONCLUSION: This study provides a resource for understanding T-cell heterogeneity and the associated prognostic risk model for TNBC. The results show that the model helps predict prognosis and response to treatment in breast cancer.

Elucidating the pharmacological effects of Compound Kushen injection on MYC-P15-CCND1 signaling pathway in nasopharyngeal carcinoma - An in vitro study.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Kushen injection (CKI) is a representative medication of Chinese herbal injection and is often used in the adjuvant treatment of nasopharyngeal carcinoma (NPC), but its antitumor mechanism is poorly understood. AIM OF THE STUDY: To preliminarily elucidate the effects and possible mechanisms of CKI on NPC. METHODS: In this work, we explored the possible molecular mechanisms of CKI against NPC by using network pharmacology and molecular docking. In addition, proteomics was used to explore the localization and quantitative information of protein in NPC C666-1 cells after the intervention of CKI, and enrichment analysis was used to obtain the potential targets and pathways. Finally, the effect and the core targets of CKI in the intervention of NPC were explored in vitro experiments. RESULTS: Network pharmacology analysis identified three active components of CKI and 13 key targets. Molecular docking analysis showed that TNF, PTEN, CCND1, MAPK3, IL6, HIF1A, MYC had high affinity with corresponding components. Then the key pathway, cell cycle and the core targets MYC, CCND1, and P15 related to the key pathway were obtained. The results of in vitro experiments showed that CKI could inhibit the proliferation, migration, and invasion of NPC 5-8F cells and C666-1 cells, induce apoptosis of C666-1 cells, and arrest cell cycle G0/G1 phase. In addition, RT-qPCR and western blot showed that the expression of P15 was up-regulated and E2F4, E2F5, c-Myc, CCND1, and P107 was down-regulated in 5-8F cells and C666-1 cells intervened by CKI. CONCLUSION: The key pathway, cell cycle and the corresponding core targets MYC, CCND1, and P15 were obtained from network pharmacology, molecular docking, and proteomics. CKI could inhibit the proliferation, migration, and invasion of NPC cells, induce apoptosis of C666-1 cells. Especially CKI may arrest cell cycle G0/G1 phase through regulating targets MYC/P15/CCND1 of cell cycle pathway.

Radiation-induced tumor immune microenvironments and potential targets for combination therapy.

As one of the four major means of cancer treatment including surgery, radiotherapy (RT), chemotherapy, immunotherapy, RT can be applied to various cancers as both a radical cancer treatment and an adjuvant treatment before or after surgery. Although RT is an important modality for cancer treatment, the consequential changes caused by RT in the tumor microenvironment (TME) have not yet been fully elucidated. RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. During RT, alterations in signaling pathways result in changes in the local immune microenvironment. However, some immune cells are immunosuppressive or transform into immunosuppressive phenotypes under specific conditions, leading to the development of radioresistance. Patients who are radioresistant respond poorly to RT and may experience cancer progression. Given that the emergence of radioresistance is inevitable, new radiosensitization treatments are urgently needed. In this review, we discuss the changes in irradiated cancer cells and immune cells in the TME under different RT regimens and describe existing and potential molecules that could be targeted to improve the therapeutic effects of RT. Overall, this review highlights the possibilities of synergistic therapy by building on existing research.

Photoelectrocatalytic oxidation of ethylene glycol on trimetallic PdAgCu nanospheres enhanced by surface plasmon resonance.

The notable surface plasmon resonance (SPR) effect of some metals has been applied to improve the efficiency of alcohol oxidation reactions, whereas the comprehensive investigation of Cu-assisted photoelectrocatalysis remains challenging. We herein successfully prepared trimetallic PdAgCu nanospheres (NSs) with abundant surface bulges for the advanced ethylene glycol oxidation reaction (EGOR) and compared them with bimetallic PdAg NSs to investigate the performance enhancement mechanism. Impressively, the as-optimized PdAgCu NSs exhibited superb mass activity and electrochemical stability. Moreover, under visible light illumination, the mass activity of PdAgCu NSs increased to 1.62 times compared to that in the dark, and in contrast, the mass activity of PdAg NSs only increased to 1.48 times that in the dark. A mechanistic study indicated that the incorporation of Cu not only strengthens the whole SPR effect of PdAgCu NSs but also further modifies the electronic structure of Pd. This work highlighted that the incorporation of Cu into PdAg NSs further enhanced the photoelectrocatalytic performance and increased noble metal atom utilization, which may provide guidance to fabricate novel and promising nanocatalysts in the field of photoelectrocatalysis.

An Upper Bound Visualization of Design Trade-Offs in Adsorbent Materials for Gas Separations: CO2 , N2 , CH4 , H2 , O2 , Xe, Kr, and Ar Adsorbents.

The last 20 years have seen many publications investigating porous solids for gas adsorption and separation. The abundance of adsorbent materials (this work identifies 1608 materials for CO2 /N2 separation alone) provides a challenge to obtaining a comprehensive view of the field, identifying leading design strategies, and selecting materials for process modeling. In 2021, the empirical bound visualization technique was applied, analogous to the Robeson upper bound from membrane science, to alkane/alkene adsorbents. These bound visualizations reveal that adsorbent materials are limited by design trade-offs between capacity, selectivity, and heat of adsorption. The current work applies the bound visualization to adsorbents for a wider range of gas pairs, including CO2 , N2 , CH4 , H2 , Xe, O2 , and Kr. How this visual tool can identify leading materials and place new material discoveries in the context of the wider field is presented. The most promising current strategies for breaking design trade-offs are discussed, along with reproducibility of published adsorption literature, and the limitations of bound visualizations. It is hoped that this work inspires new materials that push the bounds of traditional trade-offs while also considering practical aspects critical to the use of materials on an industrial scale such as cost, stability, and sustainability.

T cell-related prognostic risk model and tumor immune environment modulation in lung adenocarcinoma based on single-cell and bulk RNA sequencing.

BACKGROUND: T cells are present in all stages of tumor formation and play an important role in the tumor microenvironment. We aimed to explore the expression profile of T cell marker genes, constructed a prognostic risk model based on these genes in Lung adenocarcinoma (LUAD), and investigated the link between this risk model and the immunotherapy response. METHODS: We obtained the single-cell sequencing data of LUAD from the literature, and screened out 6 tissue biopsy samples, including 32,108 cells from patients with non-small cell lung cancer, to identify T cell marker genes in LUAD. Combined with TCGA database, a prognostic risk model based on T-cell marker gene was constructed, and the data from GEO database was used for verification. We also investigated the association between this risk model and immunotherapy response. RESULTS: Based on scRNA-seq data 1839 T-cell marker genes were identified, after which a risk model consisting of 9 gene signatures for prognosis was constructed in combination with the TCGA dataset. This risk model divided patients into high-risk and low-risk groups based on overall survival. The multivariate analysis demonstrated that the risk model was an independent prognostic factor. Analysis of immune profiles showed that high-risk groups presented discriminative immune-cell infiltrations and immune-suppressive states. Risk scores of the model were closely correlated with Linoleic acid metabolism, intestinal immune network for IgA production and drug metabolism cytochrome P450. CONCLUSION: Our study proposed a novel prognostic risk model based on T cell marker genes for LUAD patients. The survival of LUAD patients as well as treatment outcomes may be accurately predicted by the prognostic risk model, and make the high-risk population present different immune cell infiltration and immunosuppression state.

Health risks of shallow groundwater in the five basins of Shanxi, China: Geographical, geological and human activity roles.

Rapid economic development often leads to groundwater degradation, posing health risks to those who rely on it. The groundwater discharge conditions in basins are poor. The health risk of shallow groundwater in basins needs more attentions. The health risk of shallow groundwater in the five basins of Shanxi Province, China was discussed based on the hydrochemical evolution of shallow groundwater and the water quality assessment. The results showed that arsenic (As) and chromium (Cr) in the shallow groundwater of the basins caused prominent health risks followed by fluoride (F) and nitrate (NO3-). The non-carcinogenic risks of As, F and NO3- to children were higher than that to adults, and the carcinogenic risks of As and Cr were higher for adults than children. Various hydrogeochemical reactions, geological conditions, climatic factors, and human activities are closely related to groundwater health risks, and basin topography is considered as one of key factors. Water-rock interaction, dedolomitization and cation exchange are the natural processes in the evolution of groundwater hydrochemistry, while agricultural and mining activities are the anthropogenic factors causing groundwater degradation. The leaching/dilution effects of infiltration precipitation in the basin-mountain systems cause distinct temporal changes in the chemical composition and health risks of the groundwater in the basins. Differences in climate and farming practices among the basins further complicate the spatio-temporal changes. The basin-mountain system is conducive to the convergence and enrichment of water flow and solutes in the basins, which aggravates the degradation of groundwater quality. This study highlights that the combined influences of geographical and geological factors and anthropogenic activities amplify the human health risks of groundwater in the basins.

Integrated bioinformatics analysis reveals potential mechanisms associated with intestinal flora intervention in nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that imposes a huge economic burden on global public health. And the gut-liver axis theory supports the therapeutic role of intestinal flora in the development and progression of NAFLD. To this end, we designed bioinformatics study on the relationship between intestinal flora disorder and NAFLD, to explore the possible molecular mechanism of intestinal flora interfering with NAFLD. METHODS: Differentially expressed genes for NAFLD were obtained from the GEO database. And the disease genes for NAFLD and intestinal flora disorder were obtained from the disease databases. The protein-protein interaction network was established by string 11.0 database and visualized by Cytoscape 3.7.2 software. Cytoscape plug-in MCODE and cytoHubba were used to screen the potential genes of intestinal flora disorder and NAFLD, to obtain potential targets for intestinal flora to interfere in the occurrence and process of NAFLD. Enrichment analysis of potential targets was carried out using R 4.0.2 software. RESULTS: The results showed that 7 targets might be the key genes for intestinal flora to interfere with NAFLD. CCL2, IL6, IL1B, and FOS are mainly related to the occurrence and development mechanism of NAFLD, while PTGS2, SPINK1, and C5AR1 are mainly related to the intervention of intestinal flora in the occurrence and development of NAFLD. The gene function is mainly reflected in basic biological processes, including the regulation of metabolic process, epithelial development, and immune influence. The pathway is mainly related to signal transduction, immune regulation, and physiological metabolism. The TNF signaling pathway, AGE-RAGE signaling pathway in diabetic activity, and NF-Kappa B signaling pathways are important pathways for intestinal flora to interfere with NAFLD. According to the analysis results, there is a certain correlation between intestinal flora disorder and NAFLD. CONCLUSION: It is speculated that the mechanism by which intestinal flora may interfere with the occurrence and development of NAFLD is mainly related to inflammatory response and insulin resistance. Nevertheless, further research is needed to explore the specific molecular mechanisms.

An advanced network pharmacology study to explore the novel molecular mechanism of Compound Kushen Injection for treating hepatocellular carcinoma by bioinformatics and experimental verification.

BACKGROUND: Compound Kushen Injection (CKI) is a Chinese patent drug that exerts curative effects in the clinical treatment of hepatocellular carcinoma (HCC). This study aimed to explore the targets and potential pharmacological mechanisms of CKI in the treatment of HCC. METHODS: In this study, network pharmacology was used in combination with molecular biology experiments to predict and verify the molecular mechanism of CKI in the treatment of HCC. The constituents of CKI were identified by UHPLC-MS/MS and literature search. The targets corresponding to these compounds and the targets related to HCC were collected based on public databases. To screen out the potential hub targets of CKI in the treatment of HCC, a compound-HCC target network was constructed. The underlying pharmacological mechanism was explored through the subsequent enrichment analysis. Interactive Gene Expression Profiling Analysis and Kaplan-Meier plotter were used to examine the expression and prognostic value of hub genes. Furthermore, the effects of CKI on HCC were verified through molecular docking simulations and cell experiments in vitro. RESULTS: Network analysis revealed that BCHE, SRD5A2, EPHX2, ADH1C, ADH1A and CDK1 were the key targets of CKI in the treatment of HCC. Among them, only CDK1 was highly expressed in HCC tissues, while the other 5 targets were lowly expressed. Furthermore, the six hub genes were all closely related to the prognosis of HCC patients in survival analysis. Molecular docking revealed that there was an efficient binding potential between the constituents of CKI and BCHE. Experiments in vitro proved that CKI inhibited the proliferation of HepG2 cells and up-regulated SRD5A2 and ADH1A, while down-regulated CDK1 and EPHX2. CONCLUSIONS: This study revealed and verified the targets of CKI on HCC based on network pharmacology and experiments and provided a scientific reference for further mechanism research.

A novel strategy to reveal clinical advantages and molecular mechanism of aidi injection in the treatment of pancreatic cancer based on network meta-analysis and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Pancreatic cancer is a common malignancy worldwide due to its poor prognosis and high mortality rate. It is clinically proven that the combination of chemotherapeutic drugs and Traditional Chinese Medicine injections (TCMIs) significantly improves the therapeutic effect. AIM OF THE STUDY: To evaluate the efficacy and clinical benefits of TCMIs in combination with chemotherapy in the treatment of pancreatic cancer and to explore the mechanism of clinical advantage of Aidi injection. METHODS: Randomized controlled trials (RCTs) were searched in databases by NMA before December 29, 2020. WinBUGS 1.4, Stata 14.0, and R 4.0.4 software were used for calculations. All results were expressed as odds ratios and 95% credible intervals. Through the network pharmacology method, the chemical components and their targets, as well as the disease targets were further analyzed. And then, biological experiments were integrated to verify the results of network pharmacology analysis. (PROSPERO ID: CRD42021283559). RESULTS: A total of 33 RCTs with 8 TCMIs and 2011 patients were included. The results of NMA showed that Aidi injection can significantly improve the clinical efficacy (OR = 0.34, 95%CI: 0.16-0.74), and the clinical advantage was that it can significantly alleviate the leukopenia and thrombocytopenia caused by chemotherapy (OR = 5.65, 95%CI: 1.18-28.13). A total of 23 chemical compounds and 280 potential targets for Aidi injection were obtained from the online databases. Among them, there were 22 compounds, 50 targets and 211 signaling pathways closely related to leukopenia. Five genes were predicted to be core targets of ADI in alleviating leukopenia, and 2 of them (TP53 and VEGFA) were confirmed by biological experiments as regulatory targets of ADI in the treatment of PC. CONCLUSIONS: In conclusion, TCMIs in combination with chemotherapy, can improve clinical efficacy and safety in the treatment of pancreatic cancer. However, the overall evidence base is low, and large samples with multi-center RCTs are still needed to support further research findings. Aidi injection can alleviate leukopenia mainly by intervening in oxidative stress, regulating cell proliferation and apoptosis, and regulating the inflammatory response. The combined application of NMA, network pharmacology, and biological experiments provides a reference for clinical evaluation and mechanism of action exploration of other drugs.