Personalized treatment of perihilar cholangiocarcinoma based on tumor genetic and molecular characteristics.

This editorial discusses the article written by Tchilikidi et al that was published in the latest edition of the World Journal of Gastrointestinal Surgery. Genetic and molecular profiling of perihilar cholangiocarcinoma (pCCA) has identified a number of key abnormalities that drive tumor growth and spread, including pyruvate kinase M2, proline rich 11, and transcription factor 7, etc. pCCA has specific genetic and molecular features that can be used to develop personalized treatment plans. Personalized treatment approaches offer new opportunities for effectively targeting the underlying drivers of tumor growth and progression. The findings based on tumor genetic and molecular characteristics highlight the importance of developing personalized treatment strategies.

Clinical value of monitoring cytokine levels for assessing the severity of mycoplasma pneumoniae pneumonia in children.

BACKGROUND: To investigate the clinical relevance of cytokine levels in assessment of the severity of mycoplasma pneumoniae pneumonia (MPP) in children. METHODS: A retrospective study was conducted on 150 pediatric cases of MPP admitted to a local hospital in China from November 1, 2022 to October 31, 2023. These MPP cases were divided into mild (n=100) and severe (n=50) groups according to the severity of the disease. Cytokine levels, including Interferon-γ (IFN-γ), Tumor Necrosis Factor-α (TNF-α), C-reactive protein (CRP), Interleukin-6 (IL-6), Interleukin-2 (IL-2), and D-Dimer (D-D), were compared between the two groups. The diagnostic efficacy of each cytokine in assessing the severity of MPP was analyzed through Receiver Operating Characteristic (ROC) curves, and correlation between cytokine levels and disease severity was assessed using Pearson's correlation coefficient. RESULTS: The IL-2 level was significantly lower, while TNF-α, IL-6, and IFN-γ levels were significantly higher in the severe group compared to the mild group (all P<0.05). TNF-α, IFN-γ, IL-2, IL-6, CRP, and D-D were identified as factors influencing the severity of MPP (all P<0.05). The ROC curve analysis showed that the areas under the curve (AUCs) of TNF-α, IL-2, IL-6, IFN-γ, CRP, and D-D were 0.864, 0.692, 0.874, 0.949, 0.814, and 0.691, respectively (all P<0.001), indicating their diagnostic value in assessing the severity of MPP. There exists a positive correlation between IL-2 and the percentage of normal lung density on Computed Tomography (CT) scan (P<0.05), while TNF-α, IL-6, IFN-γ, CRP, and D-D showed negative correlations with the percentage of normal lung density (P<0.05). CONCLUSION: Cytokines such as TNF-α, IL-2, IL-6, IFN-γ, CRP, and D-D are aberrantly expressed in children with MPP and are associated with the severity of the disease. These cytokines have high diagnostic value and can serve as reference indicators for clinical, especially prognostic assessment of the severity of (pediatric) MPP.

On-Line Analysis of Cigarette Smoke Based on Microwave Plasma Torch Mass Spectrometry.

Cigarette smoke contains a large number of chemicals, including both flavor components and harmful substances. The mainstream smoke (MSS) generated by smoking is directly inhaled by individuals, making it crucial to establish an effective method for smoke detection and analysis. One promising technique for analyzing smoke is MPT-MS (Microwave plasma torch mass spectrometry). This approach offers several advantages in accurately detecting the composition of cigarette smoke. By combining MPT-MS with a smoke pumping device, we can achieve real-time online detection of smoke components. We successfully detected 22 flavor compounds present in the smoke. These compounds contribute to the distinct taste of cigarettes. Moreover, we identified 2 polycyclic aromatic hydrocarbons (PAHs) in the smoke. PAHs are known carcinogens and are of great concern in terms of their potential health risks. The successful detection and identification of flavor compounds and PAHs using our method confirm the online detection capability of MPT-MS. This approach provides an efficient and reliable means for analyzing the complex composition of cigarette smoke. By utilizing MPT-MS, we can gain valuable insights into the chemical composition of cigarette smoke and can inform the development of strategies and policies aimed at reducing the harmful effects of smoking and protecting public health.

Testosterone Exacerbates the Formation of Liver Cancer Induced by Environmental N-Nitrosamines Exposure: Potential Mechanisms and Implications for Human Health.

Background: Humans are frequently exposed to N-nitrosamines through various sources, including diet, cigarette smoking, contaminated water, the atmosphere, and endogenous nitrosation. Exposure to these carcinogens may also contribute to the gender-specific incidence of liver cancer, which is significantly higher in males than in females, possibly due to the influence of endogenous hormones such as testosterone. However, the effect of testosterone on N-nitrosamine-induced liver cancer and its underlying mechanism remains unclear. Purpose: To investigate the effect of testosterone on the development of liver cancer induced by N-nitrosamines exposure. Patients and Methods: Histopathological and immunohistochemical staining techniques were employed to analyze the expression levels and nuclear localizations of key signaling molecules, including androgen receptor (AR), ß-catenin, and HMGB1, in both tumor and non-tumor regions of liver samples obtained from human patients and mice. Results: The findings demonstrated a strong correlation between AR and ß-catenin in the nuclear region of tumor areas. AR also showed a significant correlation with HMGB1 in the cytoplasmic region of non-tumor areas in both human and mice samples. The study further analyzed the expression levels and patterns of these three proteins during the progression of liver tumors. Conclusion: This study confirms that AR has the ability to modulate the expression levels and patterns of ß-catenin and HMGB1 in vivo, thereby exacerbating the progression of liver cancer induced by environmental N-nitrosamines exposure. Importantly, the effect of testosterone on the formation of liver cancer induced by environmental N-nitrosamine exposure intensifies this progression. These findings have important implications for drug safety in clinical practice and emphasize the significance of reducing N-nitrosamines exposure through conscious choices regarding diet and lifestyle to ensure environmental safety.

Promotion Effect of Coexposure to a High-Fat Diet and Nano-Diethylnitrosamine on the Progression of Fatty Liver Malignant Transformation into Liver Cancer.

Overconsumption of high-fat foods increases the risk of fatty liver disease (FLD) and liver cancer with long pathogenic cycles. It is also known that the intake of the chemical poison nitrosamine and its nanopreparations can promote the development of liver injuries, such as FLD, and hepatic fibrosis, and significantly shorten the formation time of the liver cancer cycle. The present work confirmed that the coexposure of a high-fat diet (HFD) and nano-diethylnitrosamine (nano-DEN) altered the tumor microenvironment and studied the effect of this coexposure on the progression of fatty liver malignant transformation into liver cancer. Gene transcriptomics and immunostaining were used to evaluate the tumor promotion effect of the coexposure in mice. After coexposure treatment, tumor nodules were obviously increased, and inflammation levels were elevated. The liver transcriptomics analysis showed that the expression levels of inflammatory, fatty, and fibrosis-related factors in the coexposed group were increased in comparison with the nano-DEN- and high-fat-alone groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that coexposure aggravated the high expression of genes related to the carcinomatous pathway and accelerated the formation of the tumor microenvironment. The immunohistochemical staining results showed that the coexposure significantly increased the abnormal changes in proteins related to inflammation, proliferation, aging, and hypoxia in mouse liver tissues. The coexposure of high fat and nano-DEN aggravated the process of steatosis and carcinogenesis. In conclusion, the habitual consumption of pickled foods containing nitrosamines in a daily HFD significantly increases the risk of liver pathology lesions progressing from FLD to liver cancer.

Recent advances of targeting nicotinamide phosphoribosyltransferase (NAMPT) for cancer drug discovery.

Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme for the biosynthesis of NAD+ in the salvage pathway. NAMPT is overexpressed in various cancers, associating with a poor prognosis and tumor progression. Beyond cancer metabolism, recent evidence unravels additional roles of NAMPT in cancer biology, including DNA repair machinery, crosstalk with oncogenic signaling pathways, cancer cell stemness, and immune responses. NAMPT is a promising therapeutic target for cancer. However, first-generation NAMPT inhibitors exhibited limited efficacy and dose-limiting toxicities in clinical trials. Multiple strategies are being exploited to improve their efficacy and minimize toxic-side effects. This review discusses the biomarkers predictive of response to NAMPT inhibitors, and summarizes the most significant advances in the evolution of structurally distinct NAMPT inhibitors, the manipulation of targeted delivery technologies via antibody-drug conjugates (ADCs), PhotoActivated ChemoTherapy (PACT) and the intratumoral delivery system, as well as the development and pharmacological outcomes of NAMPT degraders. Finally, a discussion of future perspectives and challenges in this area is also included.

Gradual deterioration of fatty liver disease to liver cancer via inhibition of AMPK signaling pathways involved in energy-dependent disorders, cellular aging, and chronic inflammation.

Introduction: Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer kind. According to recent research, a fatty liver increases the risk of hepatocellular cancer. Nevertheless, the AMPK signaling pathway is crucial. In addition, 5'-AMP-activated protein kinase (AMPK) is strongly linked to alterations in the tumor microenvironment, such as inflammation, hypoxia, and aging. The objective of this study is to evaluate the impact of the AMPK signaling pathway on the progression of fatty liver to HCC. Methods: In this study, we established a mouse liver cancer model using high-fat diets and nano-nitrosamines (nano-DEN). In addition, we employed a transcriptomic technique to identify all mRNAs detected in liver samples at the 25th weekexpression of proteins linked with the LKB1-AMPK-mTOR signaling pathway, inflammation, aging, and hypoxia was studied in microarrays of liver cancer tissues from mice and humans. These proteins included p-AMPK, LKB1, mTOR, COX-2, ß-catenin, HMGB1, p16, and HIF-1α. Results: Data were collected at different times in the liver as well as in cancerous and paracancerous regions and analyzed by a multispectral imaging system. The results showed that most of the genes in the AMPK signaling pathway were downregulated. Prakk1 expression was upregulated compared to control group but downregulated in the cancerous regions compared to the paracancerous regions. Stk11 expression was downregulated in the cancerous regions. Mtor expression was upregulated in the cancerous regions. During liver cancer formation, deletion of LKB1 in the LKB1-AMPK-mTOR signaling pathway reduces phosphorylation of AMPK. It contributed to the upregulation of mTOR, which further led to the upregulation of HIF1α. In addition, the expression of ß-catenin, COX-2, and HMGB1 were upregulated, as well as the expression of p16 was downregulated. Discussion: These findings suggest that changes in the AMPK signaling pathway exacerbate the deterioration of disrupted energy metabolism, chronic inflammation, hypoxia, and cellular aging in the tumor microenvironment, promoting the development of fatty liver into liver cancer.

Design, synthesis, biological evaluation of urea substituted 1,2,5-oxadiazole-3-carboximidamides as novel indoleamine 2,3-dioxygenase-1 (IDO1) inhibitors.

Indoleamine 2,3-dioxygenase-1 (IDO1) has been considered as an attractive target for oncology immunotherapy due to its immunosuppressive effects on the tumor microenvironment. The most advanced IDO1 inhibitor epacadostat in combination with anti-PD-1 antibody failed to show desirable objective response. Epacadostat is now reevaluated in phase III clinical trials, but its pharmacokinetic (PK) properties are unsatisfactory. To further unravel the antitumor efficacy of IDO1 inhibitors, we designed a series of epacadostat analogues by introducing various urea-containing side chains. In particular, the most active compound 3 showed superior inhibitory potency against recombinant hIDO1 and hIDO1 in HeLa cells induced by interferon γ (IFNγ) relative to epacadostat (3, biochemical hIDO1 IC50 = 67.4 nM, HeLa hIDO1 IC50 = 17.6 nM; epacadostat, biochemical hIDO1 IC50 = 75.9 nM, HeLa hIDO1 IC50 = 20.6 nM). Moreover, compound 3 exhibited improved physicochemical properties and rat PK profile with better oral exposure and bioavailability compared with epacadostat. Importantly, this compound exhibited comparable antitumor efficacy with epacadostat in LLC syngeneic xenograft models. Hence, compound 3 represents a promising lead compound for discovery of more effective IDO1 inhibitors.

Multimodal data fusion for supervised learning-based identification of USP7 inhibitors: a systematic comparison.

Ubiquitin-specific-processing protease 7 (USP7) is a promising target protein for cancer therapy, and great attention has been given to the identification of USP7 inhibitors. Traditional virtual screening methods have now been successfully applied to discover USP7 inhibitors aiming at reducing costs and speeding up time in several studies. However, due to their unsatisfactory accuracy, it is still a difficult task to develop USP7 inhibitors. In this study, multiple supervised learning classifiers were built to distinguish active USP7 inhibitors from inactive ligands. Physicochemical descriptors, MACCS keys, ECFP4 fingerprints and SMILES were first calculated to represent the compounds in our in-house dataset. Two deep learning (DL) models and nine classical machine learning (ML) models were then constructed based on different combinations of the above molecular representations under three activity cutoff values, and a total of 15 groups of experiments (75 experiments) were implemented. The performance of the models in these experiments was evaluated, compared and discussed using a variety of metrics. The optimal models are ensemble learning models when the dataset is balanced or severely imbalanced, and SMILES-based DL performs the best when the dataset is slightly imbalanced. Meanwhile, multimodal data fusion in some cases can improve the performance of ML and DL models. In addition, SMOTE, unbiased decoy selection and SMILES enumeration can improve the performance of ML and DL models when the dataset is severely imbalanced, and SMOTE works the best. Our study established highly accurate supervised learning classification models, which would accelerate the development of USP7 inhibitors. Some guidance was also provided for drug researchers in selecting supervised models and molecular representations as well as handling imbalanced datasets.

Detection of target DNA with a visual CRISPR-associated hyperbranched rolling circle amplification technique.

This paper presents a novel clustered regularly interspaced short palindromic repeat (CRISPR)-associated HRCA technique (CART). During the entire detection process of CART, the target DNA is first specifically recognized and cleaved by a pair of Cas9/sgRNA complexes; then, the cleaved product is ligated into circular DNA as the template of HRCA, and the circular DNA is efficiently amplified by HRCA. Therefore, CART has the advantages of Cas9/sgRNA (single-base mismatch specificity) and HRCA (isothermal reaction temperature and high sensitivity). This technique has been verified by detecting various human papillomavirus (HPV) genes with numerous subtypes. In summary, this study provides a new and effective method for the detection of nucleic acids.

Acupuncture relieves the visceral pain of diarrhea-predominant irritable bowel syndrome rats by regulating P2X4 expression.

OBJECTIVES: We researched the effect and mechanism of acupuncture treatment for visceral pain in rats with diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: We set up a rat model of IBS-D with chemical and chronic- and acute-pressure stimulations. Then, the IBS-D rats were treated with acupuncture or 5-BDBD, and the therapeutic efficacy of acupuncture in IBS-D rats was assessed by means of the Bristol scale, diarrhea index, abdominal withdrawal reflex (AWR) score, mast cell count and histologic staining. RESULTS: Acupuncture significantly decreased clinical symptoms in IBS-D rats after a 14 day-treatment. Furthermore, significant down-regulation of P2X4, OX42, BDNF (brain-derived neurotrophic factor) and IRF-5 (interferon regulatory factor 5) expressions were observed in the IBS-D rats, along with the decreased inflammatory factors [interleukin 1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6)], chemokines [monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), and C-X-C motif chemokine ligand 1 (CXCL1)], and neurotransmitters [substance P (SP), 5-hydroxytryptamine (5-HT), and calcitonin gene-related peptide (CGRP)]. 5-BDBD treatment had a similar effect on IBS-D rats. CONCLUSIONS: Acupuncture can effectively alleviate abdominal pain by decreasing visceral hypersensitivity and controlling the expression of P2X4 and spinal microglial inflammation in IBS rats.

Enhanced healing of oral chemical burn by inhibiting inflammatory factors with an oral administration of shengFu oil.

ShengFu oil is a compounded Chinese medicinal prescription, and provides antibacterial, anti-inflammatory, and analgesic effects, favoring burn wound repair. In this study, we aimed at investigating the effects of topical applications of ShengFu oil and its active ingredients in oral chemical burns and elucidating its regulatory effects on ß-catenin, COX-2, and MMP-9 expression caused by exposure to acid or alkaline agents. ShengFu oil contains 16 components, such as Frankincense, Radix Scutellariae and Radix Rehmanniae, and the main active ingredients from Frankincense are α-pinene, linalool, and n-octanol. Mouse models of oral chemical burns were induced by using glacial acetic acid or sodium hydroxide. Hematoxylin and eosin staining and immunohistochemical staining were used to detect the protein expressions of ß-catenin, COX-2, and MMP-9 in wound tissues. They were further quantified by multispectral imaging analysis to clarify the effective mechanism of ShengFu oil for intervening inflammatory factors and active components. Our results indicated that the application of ShengFu oil on oral chemical burns effectively stopped the oral burn bleeding and reduced the inflammatory reaction in the damaged tissues, demonstrating that ShengFu oil can promote wound tissue repair in burns caused by heat, acids, and alkalis. The immunohistochemical staining results illustrated that ShengFu oil and its active ingredients significantly reversed the abnormal changes in inflammation-related proteins in mouse tongue tissues that were caused by chemical burns. Regarding long-term toxic effects of ShengFu oil on the gastrointestinal tract, liver, and kidney system, the results of hematoxylin and eosin staining experiments depicted that ShengFu oil was safe and effective for liver, kidney, intestine, esophagus, and tongue. All of these demonstrated that ShengFu oil and its active ingredients are effective and safe in preventing and treating oral chemical burns by interfering with the inflammatory microenvironment.

Pediatric living donor liver transplantation using liver allograft after ex vivo backtable resection of hemangioma: A case report.

BACKGROUND: Use of liver allograft with hepatic hemangioma after in vivo resection of hemangioma in living donor liver transplantation (LDLT) has been previously reported. However, there are few reports describing ex vivo backtable resection of hemangioma from liver allografts in LDLT. CASE SUMMARY: A 55-year-old male was evaluated as a donor for an 8-month-year old patient with acute hepatic failure due to biliary atresia. Pre-operative contrast enhanced computed tomography revealed a 9 cm hemangioma in segment 4 with vascular variations in the donor. During LDLT, an intra-operative intrahepatic cholangiography was performed to ensure no variation in the anatomy of the intrahepatic bile duct. After intra-operative pathological diagnosis, ex vivo backtable resection of the hemangioma was performed and the liver allograft was transplanted into the recipient. The donor's and recipient's post-operative course were uneventful. At the 2-year follow-up, the liver allograft showed good regeneration without any recurrence of hemangioma. CONCLUSION: Liver allografts with hemangiomas are an acceptable alternative strategy for LDLT. Ex vivo backtable resection of hemangioma from the donor liver during pediatric LDLT is safe and feasible, and can effectively reduce the operative time and intra-operative bleeding for the donor.

Ethanol supernatant extracts of Gynura procumbens could treat nanodiethylnitrosamine-induced mouse liver cancer by interfering with inflammatory factors for the tumor microenvironment.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynura procumbens (Lour.) Merr, (Family Asteraceae), which serves as both medicine and food in traditional ethnic medicine, has the effects of diminishing inflammation, relieving cough, reducing blood glucose and lipids levels, mitigating hepatotoxicity, and can be used for liver cancer prevention and treatment. AIM OF THE STUDY: To explore how the ethanol extract of Gynura procumbens stems (EEGS) can effectively intervene in the tumor microenvironment, it is necessary to study the mechanism of EEGS on the chemical toxicant nanodiethylnitrosamine (nanoDEN) that induces liver cancer. MATERIALS AND METHODS: EEGS contains large quantities of caffeoylquinic acid (CAC) and non-caffeoylquinic acid (n-CAC), which can be separated by high-performance liquid chromatography. The liver cancer model that was induced by the chemical toxin, nanoDEN, was used to clarify the effective mechanism for tumor intervention of the EEGS and its active ingredients. RESULTS: (1) after interventions with the four drugs on liver cancer, the tumor nodules were obviously reduced and inflammation levels improved. (2) The immunohistochemical staining results showed that both the EEGS and its active ingredients could significantly reverse the abnormal changes in inflammation, proliferation, aging and hypoxia-related proteins in mouse liver tissues that were caused by nanoDEN. (3) Real-time PCR results showed that compared with the nanoDEN group, the expression levels of inflammatory, fatty, and fibrosis-related factors in each group after drug intervention were decreased. (4) The transmission electron microscopy measurements showed that the EEGS significantly reversed the nanostructure changes in hepatocytes that were induced by nanoDEN. CONCLUSION: The EEGS component of Gynura procumbens is effective in preventing and treating liver cancer by interfering with the inflammatory microenvironment during oncogenesis induced by nanoDEN.

The function and mechanism of microRNA-92a-3p in lipopolysaccharide-induced acute lung injury.

OBJECTIVES: Sepsis-associated acute lung injury (ALI) is a clinically severe respiratory disorder and remains the leading cause of multiple organ failure and mortality. Herein, we used lipopolysaccharide (LPS) to generate sepsis-induced ALI and try to explore the role and mechanism of microRNA-92a-3p (miR-92a-3p) in this process. METHODS: Mice were intravenously injected with miR-92a-3p agomir, antagomir and negative controls for 3 consecutive days and then were intratracheally instillated by LPS (5 mg/kg) for 12 h. To knock down the endogenous A-kinase anchoring protein 1 (AKAP1), mice were intratracheally injected with recombinant adenovirus carrying the short hairpin RNA targeting AKAP1 (shAkap1) at 1 week before LPS administration. RESULTS: miR-92a-3p level was significantly upregulated in the lungs by LPS injection. miR-92a-3p antagomir reduced LPS-induced intrapulmonary inflammation and oxidative stress, thereby preventing pulmonary injury and dysfunction. In contrast, miR-92a-3p agomir aggravated LPS-induced intrapulmonary inflammation, oxidative stress, pulmonary injury and dysfunction. Moreover, we reported that AKAP1 upregulation was required for the beneficial effects of miR-92a-3p antagomir, and that AKAP1 knockdown completely abolished the anti-inflammatory and antioxidant capacities of miR-92a-3p antagomir. CONCLUSION: Our data identify that miR-92a-3p modulates LPS-induced intrapulmonary inflammation, oxidative stress and ALI via AKAP1 in mice.

MicroRNA-762 Modulates Lipopolysaccharide-induced Acute Lung Injury via SIRT7.

BACKGROUND: Inflammation and oxidative stress contribute to the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury (ALI). MicroRNA-762 (miR-762) has been implicated in the progression of inflammation and oxidative stress; however, its role in ALI remains unclear. In this study, we aim to investigate the role and underlying mechanisms of miR-762 in LPS-induced ALI. METHODS: Mice were intravenously injected with miR-762 antagomir, agomir or the negative controls for 3 consecutive days and then received a single intratracheal instillation of LPS (5 mg/kg) for 12 h to establish ALI model. Adenoviral vectors were used to knock down the endogenous SIRT7 expression. RESULTS: An increased miR-762 expression was detected in LPS-treated lungs. miR-762 antagomir significantly reduced inflammation, oxidative stress and ALI in mice, while the mice with miR-762 agomir treatment exhibited a deleterious phenotype. Besides, we found that SIRT7 upregulation was essential for the pulmonoprotective effects of miR-762 antagomir, and that SIRT7 silence completely abolished the anti-inflammatory and anti-oxidant capacities of miR-762 antagomir. CONCLUSION: miR-762 is implicated in the pathogenesis of LPS-induced ALI via modulating inflammation and oxidative stress, which depends on its regulation of SIRT7 expression. It might be a valuable therapeutic target for the treatment of ALI.

Selenium Attenuates S. aureus-Induced Inflammation by Regulation TLR2 Signaling Pathway and NLRP3 Inflammasome in RAW 264.7 Macrophages.

This study aimed to investigate the effects of selenium (Se) on the expression of Toll-like receptor (TLR) 2 and pyrin domain-containing protein (NLRP)3 inflammasome in macrophages infected by Staphylococcus aureus (S. aureus). RAW 264.7 macrophages were treated with 2 µmol/L Na2SeO3 for 12 h before infection with S. aureus for 2 h. Through Western blot, qRT-PCR, and ELISA analysis, the core molecules of TLR2 signaling pathway and NLRP3 inflammasome in RAW 264.7 macrophages were detected. Results showed that Se significantly reduced the elevated mRNA expression of TLR2, myeloid differentiation factor-88 (Myd88), NLRP3, Caspase-recruitment domain (ASC), and Caspase-1 induced by S. aureus. Furthermore, compared with I group, the protein expression of TLR2, Myd88, NLRP3, ASC, and Caspase-1 were suppressed in T group. In addition, the mRNA and protein expression of interleukin-1 beta (IL-1ß) induced by S. aureus were also decreased after Se treatment. In conclusion, Se inhibits S. aureus-induced inflammation by suppressing the activation of the TLR2 signaling pathway and NLRP3 inflammasome in RAW 264.7 macrophages.

Short Communication: Effects of Dietary Selenium Supplementation on Selenium Deposition and Antioxidant Status in Postpartum Mice.

This study aimed to investigate the effects of dietary selenium during pregnancy on the selenium deposition and antioxidant enzymes in postpartum mouse serum, liver, and mammary gland. Eighty BALB/c pregnant mice were randomly divided into four groups: CG (Se-deficient basal diet, n = 20), LG (0.05 mg/kg Se-supplemented diet, n = 20), MG (0.1 mg/kg Se-supplemented diet, n = 20), and HG (0.2 mg/kg Se-supplemented diet, n = 20). Four days after parturition, all mice were euthanized. The selenium deposition and antioxidants enzymes in serum, liver, and mammary gland were detected. Results show that with increasing selenium supplementation, the selenium deposition and activation of T-AOC, T-SOD, and GSH-Px increased, meanwhile the concentration of MDA decreased in serum, liver, and mammary gland. Therefore, this study suggested selenium was mainly deposited in the liver, and dietary selenium during pregnancy might improve the antioxidant status in postpartum animals.

What is the difference in ablation zone of multi-bipolar radiofrequency ablation between liver cirrhosis and normal liver background? - a prospective clinical study.

PURPOSE: To explore the differences in ablation zone between liver cirrhosis and normal liver background and investigate the effect of hepatic blood flow on ablation zone of RFA. METHODS: Between 2017 and 2019, 203 patients who had liver malignancies and underwent percutaneous RFA with Celon bipolar electrodes enrolled into this study. There were 90 patients had liver cirrhosis and 113 patients had normal liver background. They were 63 females and 140 males with average age of 59.0 ± 10.9 years old. Contrast-enhanced CT/MRI was used to evaluate the ablation zone in one month after RFA. The hepatic flow measurements on CDFI and CEUS were performed before RFA. Correlations between ablation zone versus hepatic flow were assessed using multiple linear regression analysis. RESULTS: The average ablation zone in cirrhotic liver was significantly larger than those in normal liver background with 3 cm tip of RF electrodes (length 3.5 ± 0.5 vs 3.1 ± 0.4 cm, p = 0.001; width 2.6 ± 0.3 vs 2.2 ± 0.3 cm, p < 0.001; thickness 2.5 ± 0.3 vs 2.0 ± 0.2 cm, p < 0.001). The similar result was found with three 4 cm tip of RF electrodes (width 3.6 ± 0.5 vs 3.1 ± 0.5 cm, p = 0.019; thickness 3.3 ± 0.5 vs 2.7 ± 0.5 cm, p = 0.002). The multiple linear regression analysis showed arrive time of hepatic vein and portal vein was statistically associated with ablation zone with 3 cm electrodes (p < 0.001, p = 0.001), but explained part of the variance (Adjusted R2=0.294, adjusted R2=0.212). CONCLUSION: The ablation zones of RFA with multi-bipolar electrodes in liver cirrhosis were significantly larger than those in normal liver background, being up to 6 mm in thickness. The hepatic flow parameters partly contributed to the ablation zone.

Fast-growing epithelioid hemangioendothelioma of the liver: A case report.

RATIONALE: Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of the liver with malignant potential. It can be of solitary type, multifocal type, or diffuse type. Although there are some characteristic features on radiologic imaging, the definitive diagnosis of HEH is based on histopathology. The surgical treatment of HEH includes liver resection and transplant. PATIENT CONCERNS: A middle-aged woman presented with easy fatiguability and anorexia for 1 month was found to have multifocal lesions on radiological imaging. DIAGNOSIS: HEH was diagnosed by needle biopsy. It can be seen from imaging that this case is a multifocal form. The largest lesion increased from 3 to 3.3 cm within 2 months, with an increase of 9.45%; no other relevant literatures have been reported. INTERVENTIONS: The possibility of liver transplantation was suggested to the patient. However, the patient refused transplantation and was successfully treated by radical right hepatectomy and resection of the left lobe lesion. OUTCOMES: She remained disease-free throughout a year follow-up period. CONCLUSION: HEH is a rare disease with characteristic radiological and pathological features. Although liver transplantation is the preferred treatment for multifocal HEH, surgical excision represents one alternative when the lesions can be guaranteed to be completely excised.