Endovascular Repair Blunt Thoracic Aortic Injury in Adolescent: A Case Series.

BACKGROUND: Blunt traumatic aortic injury (BTAI) is a rare occurrence in adolescents, yet it is associated with a high mortality rate necessitating immediate treatment. Although endovascular repair has become the preferred treatment for such injuries in adults, its effectiveness in adolescents remains uncertain. CASE SUMMARY: Blunt traumatic aortic injury typically presents with concomitant injuries to other organs and carries a high perioperative mortality rate with operative repair (OR). In this report, we describe the treatment of 3 clinical cases of BTAI in adolescents using thoracic endovascular aortic repair (TEVAR). These cases contribute pertinent evidence supporting the efficacy of intravascular repair for BTAI. CONCLUSION: Operative repair (OR) remains the gold standard for treating BTAI in adolescents. Nevertheless, TEVAR therapy presents a viable alternative for patients with multiple injuries in whom anticoagulation is contraindicated. Further long-term observation is necessary to assess the lasting effects of TEVAR therapy. CLINICAL IMPACT: This study has provided insights into endovascular repair for adolescent BTAT, offering clinicians significant reference material for choosing treatment strategies for adolescent BTAT. The study aims to demonstrate the safety and effectiveness of endovascular repair treatments in a series of clinical cases involving adolescent BTAI.

Constructing regulable supports via non-stoichiometric engineering to stabilize ruthenium nanoparticles for enhanced pH-universal water splitting.

Establishing appropriate metal-support interactions is imperative for acquiring efficient and corrosion-resistant catalysts for water splitting. Herein, the interaction mechanism between Ru nanoparticles and a series of titanium oxides, including TiO, Ti4O7 and TiO2, designed via facile non-stoichiometric engineering is systematically studied. Ti4O7, with the unique band structure, high conductivity and chemical stability, endows with ingenious metal-support interaction through interfacial Ti-O-Ru units, which stabilizes Ru species during OER and triggers hydrogen spillover to accelerate HER kinetics. As expected, Ru/Ti4O7 displays ultralow overpotentials of 8 mV and 150 mV for HER and OER with a long operation of 500 h at 10 mA cm-2 in acidic media, which is expanded in pH-universal environments. Benefitting from the excellent bifunctional performance, the proton exchange membrane and anion exchange membrane electrolyzer assembled with Ru/Ti4O7 achieves superior performance and robust operation. The work paves the way for efficient energy conversion devices.

Crosstalk between endothelial progenitor cells and HCC through periostin/CCL2/CD36 supports formation of the pro-metastatic microenvironment in HCC.

Metastasis causes most cancer-related deaths, and the role and mechanism of periostin (POSTN) in the metastasis of hepatocellular carcinoma (HCC) remain undiscovered. In this study, DEN and HTVi HCC models were performed in hepatic-specific Postn ablation and Postn knock-in mouse to reveal the role of POSTN in HCC metastasis. Furthermore, POSTN was positively correlated with circulating EPCs level and promoted EPC mobilization and tumour infiltration. POSTN also mediated the crosstalk between HCC and EPCs, which promoted metastasis ability and upregulated CD36 expression in HCC through indirect crosstalk. Chemokine arrays further revealed that hepatic-derived POSTN induced elevated CCL2 expression and secretion in EPCs, and CCL2 promoted prometastatic traits in HCC. Mechanistic studies showed that POSTN upregulated CCL2 expression in EPCs via the αvß3/ILK/NF-κB pathway. CCL2 further induced CD36 expression via the CCR2/STAT3 pathway by directly binding to the promoter region of CD36. Finally, CD36 was verified to have a prometastatic role in vitro and to be correlated with POSTN expression, metastasis and recurrence in HCC in clinical samples. Our findings revealed that crosstalk between HCC and EPCs is mediated by periostin/CCL2/CD36 signalling which promotes HCC metastasis and emphasizes a potential therapeutic strategy for preventing HCC metastasis.

Prognostic value of diffuse reduction of spleen density on postoperative survival of pancreatic ductal adenocarcinoma: A retrospective study.

PURPOSE: It is difficult to predict the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) before radical operation. The purpose of this study was to explore the connection between the diffuse reduction of spleen density on computed tomography (DROSD) and the postoperative prognosis of patients with PDAC. PATIENTS AND METHODS: A total of 160 patients with PDAC who underwent radical surgery in the First Affiliated Hospital of Wenzhou Medical University were enrolled. Cox regression analysis was used to cast the overall survival (OS) and evaluate the prognostic factors. Nomogram was used to forecast the possibility of 1-year, 3-year, and 5-year OS. The prediction accuracy and clinical net benefit are performed by concordance index (C-index), calibration curve, time-dependent receiver operating characteristics (tdROC), and decision curve analysis. RESULTS: In multivariable Cox analysis, DROSD is independently related to OS. Advanced age, TNM stage, neutrophil/lymphocyte ratio, and severe complications were also independent prognostic factors. The calibration curves of nomogram showed optimal agreement between prediction and observation. The C-index of nomogram is 0.662 (95%CI, 0.606-0.754). The area under tdROC curve for a 3-year OS of nomogram is 0.770. CONCLUSION: DROSD is an independent risk factor for an OS of PDAC. We developed a nomogram that combined imaging features, clinicopathological factors, and systemic inflammatory response to provide a personalized risk assessment for patients with PDAC.

AZGP1 activation by lenvatinib suppresses intrahepatic cholangiocarcinoma epithelial-mesenchymal transition through the TGF-ß1/Smad3 pathway.

Intrahepatic cholangiocarcinoma (ICC) is a primary liver malignancy and is characterized by highly aggressive and malignant biological behavior. Currently, effective treatment strategies are limited. The effect of lenvatinib on ICC is unknown. In this study, we found that AZGP1 was the key target of lenvatinib in ICC, and its low expression in ICC cancer tissues was associated with a poor prognosis in patients. Lenvatinib is a novel AZGP1 agonist candidate for ICC that inhibits ICC-EMT by regulating the TGF-ß1/Smad3 signaling pathway in an AZGP1-dependent manner. Furthermore, we found that lenvatinib could increase AZGP1 expression by increasing the acetylation level of H3K27Ac in the promoter region of the AZGP1 gene, thereby inhibiting EMT in ICC cells. In conclusion, lenvatinib activates AZGP1 by increasing the acetylation level of H3K27Ac on the AZGP1 promoter region and regulates the TGF-ß1/Smad3 signaling pathway in an AZGP1-dependent manner to inhibit ICC-EMT. This study offers new insight into the mechanism of lenvatinib in the treatment of ICC and provides a theoretical basis for new treatment methods.

Valence Oscillation of Ru Active Sites for Efficient and Robust Acidic Water Oxidation.

The continuous oxidation and leachability of active sites in Ru-based catalysts hinder practical application in proton-exchange membrane water electrolyzers (PEMWE). Herein, robust inter-doped tungsten-ruthenium oxide heterostructures [(Ru-W)Ox ] fabricated by sequential rapid oxidation and metal thermomigration processes are proposed to enhance the activity and stability of acidic oxygen evolution reaction (OER). The introduction of high-valent W species induces the valence oscillation of the Ru sites during OER, facilitating the cyclic transition of the active metal oxidation states and maintaining the continuous operation of the active sites. The preferential oxidation of W species and electronic gain of Ru sites in the inter-doped heterostructure significantly stabilize RuOx on WOx substrates beyond the Pourbaix stability limit of bare RuO2 . Furthermore, the asymmetric Ru-O-W active units are generated around the heterostructure interface to adsorb the oxygen intermediates synergistically, enhancing the intrinsic OER activity. Consequently, the inter-doped (Ru-W)Ox heterostructures not only demonstrate an overpotential of 170 mV at 10 mA cm-2 and excellent stability of 300 h in acidic electrolytes but also exhibit the potential for practical applications, as evidenced by the stable operation at 0.5 A cm-2 for 300 h in PEMWE.

The mixed-order chlorine decay model with an analytical solution and corresponding trihalomethane generation model in drinking water.

Ensuring effective drinking water disinfection, remaining a certain amount of residual chlorine, and controlling disinfection by-product formation were very important for guarantying water quality safety and protecting public health; thus, the chlorine decay model and corresponding disinfection by-product formation model were necessary. This paper proposed a mixed-order chlorine bulk decay model (two parameters) based on Taylor's formula and derived its analytical solution. The accuracy of the mixed-order model was evaluated by comparing it with the nth-order model. To optimize the model and reduce the number of parameters required to be calibrated, the relationship of parameters with temperature, initial chlorine concentration, TOC and inorganic substance (ammonia nitrogen and iodide ion) was explored. The result proved that one of the parameters could be regarded as temperature dependent only. Meanwhile, the temperature equation of the model parameters was established by the Arrhenius formula. Subsequently, this paper selected trihalomethane as the target and study the linear relationship between chlorine consumption and trihalomethane formation. The results indicated that the liner slope had little correlation with initial chlorine concentration and temperature. On this basis, the corresponding trihalomethane model was built and its performance was proven to be good. The modeling developed in this work could be applied to drinking water distribution systems for residual chlorine and trihalomethane prediction, and provided a reference for the decision involving water quality.

Activity-Stability Balance: The Role of Electron Supply Effect of Support in Acidic Oxygen Evolution.

Developing efficient and durable electrocatalysts for the oxygen evolution reaction (OER) in proton exchange membrane (PEM) electrolyzers represents a significant challenge. Herein, the cobalt-ruthenium oxide nano-heterostructures are successfully synthesized on carbon cloth (CoOx /RuOx -CC) for acidic OER through a simple and fast solution combustion strategy. The rapid oxidation process endows CoOx /RuOx -CC with abundant interfacial sites and defect structures, which enhances the number of active sites and the charge transfer at the electrolyte-catalyst interface, promoting the OER kinetics. Moreover, the electron supply effect of the CoOx support allows electrons to transfer from Co to Ru sites during the OER process, which is beneficial to alleviate the ion leaching and over-oxidation of Ru sites, improving the catalyst activity and stability. As a self-supported electrocatalyst, CoOx /RuOx -CC displays an ultralow overpotential of 180 mV at 10 mA cm-2 for OER. Notably, the PEM electrolyzer using CoOx /RuOx -CC as the anode can be operated at 100 mA cm-2 stably for 100 h. Mechanistic analysis shows that the strong catalyst-support interaction is beneficial to redistribute the electronic structure of RuO bond to weaken its covalency, thereby optimizing the binding energy of OER intermediates and lowering the reaction energy barrier.

"We may conclude that:" a corpus-based study of stance-taking in conclusion sections of RAs across cultures and disciplines.

Research article conclusions form an important sub-genre in the academic community. This study aims to compare the use of stance markers in English and Chinese research article conclusions and investigate how stance markers may vary in soft and hard sciences. Based on Hyland's stance model, an analysis of stance markers over 20 years was made in two corpora, which were compiled with 180 research article conclusions in each language from four disciplines. It was found that English writers and soft science writers tended to make statements more tentatively by hedges and craft their persona more explicitly through self-mentions. However, Chinese writers and hard science writers made their claims with more certainty by boosters and showed their affective attitude more frequently through attitude markers. The results reveal how writers from different cultural backgrounds construct their stances and also unveil the disciplinary differences involved in stance-taking. It is hoped that this corpus study will inspire future research on stance-taking in the conclusion section and also help cultivate writers' genre awareness.

Discovery of the First-in-Class Intestinal Restricted FXR and FABP1 Dual Modulator ZLY28 for the Treatment of Nonalcoholic Fatty Liver Disease.

The prevalence of nonalcoholic steatohepatitis (NASH) is increasing rapidly worldwide, and NASH has become a serious problem for human health. Recently, the selective activation of the intestinal farnesoid X receptor (FXR) was considered as a more promising strategy for the treatment of NASH with lesser side effects due to reduced systemic exposure. Moreover, the inhibition of intestinal fatty acid binding protein 1 (FABP1) alleviated obesity and NASH by reducing dietary fatty acid uptake. In this study, the first-in-class intestinal restricted FXR and FABP1 dual-target modulator ZLY28 was discovered by comprehensive multiparameter optimization studies. The reduced systemic exposure of ZLY28 might provide better safety by decreasing the on- and off-target side effects in vivo. In NASH mice, ZLY28 exerted robust anti-NASH effects by inhibiting FABP1 and activating the FXR-FGF15 signaling pathway in the ileum. With the above attractive efficacy and preliminary safety profiles, ZLY28 is worthy of further evaluation as a novel anti-NASH agent.

Cu-based perovskite as a novel CWPO catalyst for petroleum refining wastewater treatment: Performance, toxicity and mechanism.

For the first time, Cu-based perovskite oxides were used as catalysts to treat highly toxic and refractory petroleum refining wastewater based on catalytic wet peroxide oxidation (CWPO) technology. Perovskite La2CuO4 was synthesized by sol-gel method. A series of characterizations showed that the synthesized catalyst particles are tetragonal phase perovskite structure. The experimental results showed that under the conditions of catalyst dosage of 0.75 g, temperature of 100 â„ƒ and reaction time of 30 min, the COD removal rate was 89.58 %, the TOC removal rate was 87.38 %. The morphology and structure of the catalyst before and after the reaction proved that the catalyst has strong stability and catalytic activity. The components of raw water, Wet Air Oxidation (WAO) effluent and CWPO effluent were compared and analyzed by Gas Chromatography-Mass Spectrometry (GC-MS), and the possible mechanism and path of WAO and CWPO degradation of petroleum refining wastewater were further explored. The changes of Cu components in La2CuO4 before and after CWPO reaction and the transformation of lattice oxygen and adsorbed oxygen were analyzed by X-ray Photoelectron Spectroscopy (XPS). The involvement of Cu (Ⅱ) /Cu (Ⅰ) in the activation of H2O2 was speculated. Finally, the biotoxicity of raw water, WAO effluent and CWPO effluent was predicted. The results provide reference value for the application of catalyst La2CuO4 in various petrochemical wastewater.

A comprehensive study of potentially toxic element contamination and source quantitative assessment by positive matrix factorization model: risk from the fine road dust of Chehe mining area, China.

Extreme mining activities can risk human life and the environment via potentially toxic elements (PTEs) in road dust, thus making their quantification and assessment unavoidable. For this purpose, we collected 50 fine road dust samples from the Chehe mining area, China, to quantify the level of contamination and ecological and health risks of PTEs comprising As, Cd, Co, Cr, Cu, Mn, Ni, Pb, Sb, and Zn, and their quantitative source apportionment using the positive matrix factorization model (PMF). Results indicated that the average values of Cd, Sb, As, Zn, Pb, and Cu in road dust were 1555.21, 586.78, 429.68, 429.43, 72.88, and 26.61 times higher than their background values. Pollution indices of PTEs revealed a strong level of contamination by Cd, Sb, As, Zn, and Pb, which were extremely polluted in the study area. The average values of the Nemerow integrated risk index (NIRI) and potential ecological risk index (RI) were 104.09 and 86.49 times the highest risk limit, respectively, which are extremely high ecological risks. Based on PMF for quantitative source identification, mining activities and fuel combustion were the main sources of PTEs in road dust contributing 57.25% and 35.95%, respectively. Furthermore, the health risk assessment indicated that Sb, As, Cr, Cd, and Pb in the Chehe road dust could lead to significantly serious carcinogenic and non-carcinogenic risks to both children and adults. The results of this study could be used to opt for strategies to mitigate the ecological and human health risk in the mining area of Hechi, China.

Morphological characterization, hazardous metal contamination, source identification, and health risk assessment of the fine road dust from Dachang mining area, China.

Dachang mining area in China is known as "paradise for mineralogists" due to its most reserves of Sn, Sb, Pb, and Zn non-ferrous metal resources; thus, its evaluation for heavy metal assessment and consequent health risk is unavoidable. Sixty road dust samples were collected from study area to explore pollution level, ecological, and health risks from heavy metals and were analyzed by an inductively coupled plasma optical emission spectrometer and atomic fluorescence spectrometer. The results showed that average concentration of all the heavy metals in road dust in both mining and residential areas were remarkable higher than its corresponding background values, the former being more severe, except for Cr and Co. The morphological investigation showed that most of the particles were much less than 100 µm illustrating fine part of the road dust samples. Based on integrated pollution indices, Cd, Sb, As, Zn, and Pb were extremely contaminated and exceeded hundred times of the maximum risk value. The health risk assessment revealed substantially higher carcinogenic and non-carcinogenic risks to children and adult. Highest non-carcinogenic risk resulted from arsenic in mining and residential area with HQing of 644.56 and 267.94 respectively (standard HQ ≥ 1) while carcinogenic risk to children (1.94E + 00) which greatly exceeded from the threshold value of (1.0E-4). Sb, Cd, and Pb also posed carcinogenic and non-carcinogenic risk in road dust which is caused by excessive mining activities and heavy vehicle movement in the study area.

CAFs-derived SCUBE1 promotes malignancy and stemness through the Shh/Gli1 pathway in hepatocellular carcinoma.

BACKGROUND: The tumour microenvironment and cirrhotic liver are excellent sources of cancer-associated fibroblasts (CAFs), which participate in carcinogenesis. Thus, it is important to clarify the crosstalk between CAFs and HCC cells and the related mechanism in regulating carcinogenesis. METHODS: Human hepatocellular carcinoma (HCC) tissues and matched adjacent normal tissues were obtained from HCC patients. Immunohistochemistry, Western blotting (WB) and RT-qPCR were performed to detect the expression of SCUBE1. The roles of SCUBE1 in inducing stemness features in HCC cells were explored and investigated in vitro and in vivo. Student's t tests or Mann-Whitney U tests were used to compare continuous variables, while chi-square tests or Fisher's exact tests were used to compare categorical variables between two groups. RESULTS: SCUBE1 was confirmed to be highly expressed in CAFs in HCC and had a strong connection with stemness and a poor prognosis. In addition, CAFs were found to secrete SCUBE1 to enhance the malignancy of HCC cells and increase the proportion of CD133-positive cells. Silencing SCUBE1 expression had the opposite effect. The Shh pathway was activated by SCUBE1 stimulation. Inhibition of cyclopamine partially reversed the stimulating effect of SCUBE1 both in vivo and in vitro. Moreover, based on the RT-qPCR, ELISA and WB results, a high SCUBE1 expression level was found in HCC tissue and serum. CONCLUSION: This study revealed that CAFs-derived SCUBE1 can enhance the malignancy and stemness of HCC cells through the Shh pathway. This study aims to provide new perspectives for future HCC studies and provide new strategies for HCC treatment.

Retraction: A near-infrared laser and H2O2 activated bio-nanoreactor for enhanced photodynamic therapy of hypoxic tumors.

Retraction of 'A near-infrared laser and H2O2 activated bio-nanoreactor for enhanced photodynamic therapy of hypoxic tumors' by Liming Deng et al., Biomater. Sci., 2020, 8, 858-870, https://doi.org/10.1039/C9BM01126A.

Rapid complete reconfiguration induced actual active species for industrial hydrogen evolution reaction.

Rational regulation of electrochemical reconfiguration and exploration of activity origin are important foundations for realizing the optimization of electrocatalyst activity, but rather challenging. Herein, we potentially develop a rapid complete reconfiguration strategy for the heterostructures of CoC2O4 coated by MXene nanosheets (CoC2O4@MXene) during the hydrogen evolution reaction (HER) process. The self-assembled CoC2O4@MXene nanotubular structure has high electronic accessibility and abundant electrolyte diffusion channels, which favor the rapid complete reconfiguration. Such rapid reconfiguration creates new actual catalytic active species of Co(OH)2 transformed from CoC2O4, which is coupled with MXene to facilitate charge transfer and decrease the free energy of the Volmer step toward fast HER kinetics. The reconfigured components require low overpotentials of 28 and 216 mV at 10 and 1000 mA cm-2 in alkaline conditions and decent activity and stability in natural seawater. This work gives new insights for understanding the actual active species formation during HER and opens up a new way toward high-performance electrocatalysts.

Impact of sarcopenia on outcomes of patients undergoing liver resection for hepatocellular carcinoma.

BACKGROUND: Previous studies have indicated that sarcopenia is associated with poor post-operative outcomes in liver cancer patients, but the studies are limited by confounding from mixed diseases, retrospective data, and non-standardized measurement methods. At present, there is no research with both muscle mass and strength as predictors for hepatocellular carcinoma (HCC) outcomes. We studied the impact of sarcopenia on post-operative outcomes in HCC patients in a cohort study designed according to the European Working Group on Sarcopenia in Older People standards. METHODS: A total of 781 consecutive patients admitted to our centre were registered from May 2020 to August 2021. All participants submitted questionnaires and underwent handgrip strength, chair stand test, physical performance, and computed tomographic evaluation. Then, they were divided into three groups according to muscle mass and strength: Group A (reduced muscle mass and strength), Group B (reduced muscle strength or reduced muscle mass), and Group C (normal muscle mass and strength). The baseline data and post-operative outcomes were compared and analysed. The primary outcome variable in this study was the presence of a major post-operative complication, and the secondary outcome was the 90-day re-admission rate. RESULTS: A total of 155 patients [median age, 60.00 (IQR, 51.00-66.00) years; 20 females (12.90%)] were included after strict exclusion. The mean (SD) BMI was 23.37 ± 0.23 kg/m2 . The mean (SD) SMI of all participants was 47.05 ± 0.79 cm2 /m2 , and the mean (SD) handgrip strength was 32.84 ± 0.69 kg. Among them, 77 (49.68%) patients underwent laparoscopic hepatectomy, and 73 (47.10%) patients received major hepatectomy. Regarding the post-operative results, Group A had a higher rate of major complications [40.91% (9 of 22) vs. 11.94% (8 of 67) in Group B and 6.06 (4 of 66) in Group C; P = 0.001], higher rate of blood transfusion (77.27% vs. 46.27% in Group B and 42.42% in Group C; P = 0.015), higher hospitalization expenses (P = 0.001), and longer hospital stay (P < 0.001). There was no difference in 90-day re-admission rates among the three groups. Sarcopenia (hazard ratio, 10.735; 95% CI, 2.547-45.244; P = 0.001) and open surgery (hazard ratio, 4.528; 95% CI, 1.425-14.387; P = 0.010) were independent risk factors associated with major complications. CONCLUSIONS: Sarcopenia is associated with adverse outcomes after liver resection for HCC. It should be evaluated upon admission to classify high-risk patients and reduce the risk of major complications.

Development and validation of a nomogram for predicting the cancer-specific survival of fibrolamellar hepatocellular carcinoma patients.

Fibrolamellar hepatocellular carcinoma (FLC) is a rare subtype of hepatocellular carcinoma. Our study aimed to construct a nomogram to predict the cancer-specific survival (CSS) of FLC. Data of 200 FLC patients enrolled in the Surveillance, Epidemiology, and End Results (SEER) database were divided into the training group and the validation group. Prognostic factors identified in the univariate and multivariate Cox regression analyses were used to construct the nomogram. The concordance index (C-index), calibration curves, time-dependent receiver operating characteristic curve (ROC), and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. As a result, age ≥ 59, N1 stage, M1 stage, tumor size ≤ 2.0 cm, and no surgery were significantly associated with lower CSS in multivariate Cox regression analysis. The calibration plot showed good consistency of the nomogram between predicted and observed outcomes in the training and validation groups. Compared with the TNM staging system, the prognostic evaluation model (PEM) showed a higher C-index (0.823 vs 0.656). The PEM also showed better predictive performance, with areas under the curve of 0.909 and 0.890 for predicting the 1- and 5-year survival. The AUCs of the TNM stage model for predicting 1- and 5-year survival were 0.629 and 0.787, respectively. In addition, the DCA curve showed that the nomogram had better clinical utility. Finally, we concluded that Age, N stage, M stage, tumor size, and surgery are independent prognostic factors for FLC. PEM established based on these five prognostic indicators can help predict the CSS of patients with FLC.

Source-specific ecological risk assessment and quantitative source apportionment of heavy metals in surface sediments of Pearl River Estuary, China.

In this study, surface sediments of the Pearl River Estuary were collected from 29 stations and investigated the spatial distribution, pollution level, quantitative source apportionment, and source-specific ecological risk of 10 heavy metals. The mean concentrations followed the order of Mn > Zn > Cr > Cu > Ni > Pb > As > Co > Cd > Hg. In terms of spatial distribution, it showed that the heavy metals were enriched in the inner Pearl River Estuary with 'extremely high' level of Hg, whereas, Cd and Zn posed 'moderate to high' contamination potential. We apportioned four main sources using positive matrix factorization model, in which natural geogenic and industrial manufacturing sources accounted for 36.84% and 27.11% of the total, respectively. However, the source-specific risk assessment suggested that mixed anthropogenic sources were the main contributors, and ecological risks were strongly affected by anthropogenic imports from the surrounding cities.

Gut microbiome alteration as a diagnostic tool and associated with inflammatory response marker in primary liver cancer.

BACKGROUND: Primary liver cancer has high mortality and morbidity worldwide. However, the characteristic of gut microbiota profile and its correlation with inflammation status in liver cancer patients remains largely unknown, and a gut microbiome-based diagnostic model for liver cancer is still absent. METHODS: Here, we provided a comprehensive analysis based on fecal 16S rRNA sequencing and clinical data in a cohort consisting of 40 healthy volunteers, 143 hepatocellular carcinoma (HCC) patients, and 46 cholangiocarcinoma (CCA) patients. RESULTS: Our results indicated a distinct shift of gut microbiota composition between two primary liver cancer types and compared with healthy volunteers. Based on the diversity constitute of gut microbiome taxonomy and random forest algorithm, eight genera with mean abundance above 0.1% were selected to construct the classification model with half of the randomly selected cohort. Based on this signature, high diagnostic accuracy in the validation cohort to classify liver cancer types (AUC = 0.989, 0.967, 0.920 for Control, HCC, CCA separately) was achieved. Further analysis showed increased Gram-negative bacteria and elevated inflammatory response markers in CCA group versus HCC group. The correlation analysis between inflammatory response markers and composition of gut microbiome revealed decreased potentially beneficial genus and increased opportunistic pathogens positively correlated with adverse prognostic inflammatory response markers. CONCLUSION: Generally, our study established the gut microbiome-based signature for liver cancer prediction and screening and revealed that gut microbiome characteristic in primary liver cancer was correlated with adverse inflammatory response markers in liver cancer.