Microvascular invasion is associated with poor survival in patients with dual-phenotype hepatocellular carcinoma.

OBJECTIVES: Microvascular invasion (MVI) has previously been reported to be related to cancer prognosis; however, its significance in patients with dual-phenotype hepatocellular carcinoma (DPHCC) remains uncharacterized. We studied the role of MVI in the survival of patients diagnosed with DPHCC in Fujian, China, which has a high incidence of HCC. METHODS: Patients with DPHCC (n = 84) who had undergone surgical interventions at the 900th Hospital of the Joint Logistic Support Force between 2013 and 2019 were retrospectively analyzed using the log-rank test and Kaplan-Meier method. Univariate and multivariate Cox model analyses were also conducted to further understand the correlation between MVI and patient survival. RESULTS: Our results indicated that MVI was related to poor survival. According to the univariate analysis, MVI, the number of tumor lesions, necrosis, differentiation, peripheral hepatic fibrosis, the expression of cytokeratin 19 (CK19), and serum levels of both ɑ-fetoprotein (AFP) and cancer antigen-199 showed a strong correlation with overall survival. Necrosis and serum AFP levels were strongly related to an increased risk of death, according to the multivariate analysis. Tumor size; the number of tumor lesions; differentiation; peripheral hepatic fibrosis; liver capsule invasion; and expression of CK19, vascular endothelial growth factor, CK7, and mucin 1 showed a correlation with MVI, per the outcomes of χ2 tests. CONCLUSIONS: Microvascular invasion may correlate with the survival of patients with DPHCC and could potentially serve as a prognostic predictor of survival.

Metabolomics Study Revealing Purines as Potential Diagnostic Biomarkers of Acute Respiratory Distress Syndrome in Patients with Community─Acquired Pneumonia.

Community-acquired pneumonia (CAP) is a significant threat to human health and the leading cause of acute respiratory distress syndrome (ARDS). We aimed to reveal the metabolic profiling whether can be used for assessing CAP with or without ARDS (nARDS) and therapeutic effects on CAP patients after treatment. Urine samples were collected at the onset and recovery periods, and metabolomics was employed to identify robust biomarkers. 19 metabolites were significantly changed in the ARDS relative to nARDS, mainly involving purines and fatty acids. After treatment, 7 metabolites in the nARDS and 14 in the ARDS were found to be significantly dysregulated, including fatty acids and amino acids. In the validation cohort, we observed that the biomarker panel consisted of N2,N2-dimethylguanosine, 1-methyladenosine, 3-methylguanine, 1-methyladenosine, and uric acid exhibited better AUCs of 0.900 than pneumonia severity index and acute physiology and chronic health evaluation II (APACHE II) scores between the ARDS and nARDS. Combining L-phenylalanine, phytosphingosine, and N-acetylaspartylglutamate as biomarkers for discriminating the nARDS and ARDS patients after treatment exhibited good AUCs of 0.811 and 0.821, respectively. The metabolic pathway and defined biomarkers may serve as crucial indicators for predicting the development of ARDS in CAP patients and for assessing therapeutic effects.

Pathological characteristics of liver injury induced by N,N-dimethylformamide: From humans to animal models.

N,N-Dimethylformamide (DMF) is widely used in chemical industries because of its excellent solvent properties. Poisoning accidents caused by DMF have been frequently reported, particularly hepatotoxicity; however, the hepatic pathological changes have rarely been described. This study aimed to summarise the pathological characteristics of the hepatotoxicity associated with DMF in clinical cases and to verify in animal models. Liver pathologies of two patients with liver failure due to DMF were retrospectively analysed. Thirty-six rats were categorised into the DMF group (intraperitoneally injected with 4 g/kg DMF once a week), carbon tetrachloride (CCl4) group (intraperitoneally injected with 0.5 g/kg CCl4 twice a week) and control group (intraperitoneally injected with normal saline once a week). The general condition and changes in hepatic pathology at 48 h and 8 weeks were observed. Liver tissues of patients exhibited multiple unevenly distributed inflammatory and fibrotic lesions. The DMF-induced liver injury animal model was successfully established. Inflammation and fibrosis were heterogeneously observed throughout the liver in the DMF group, contrast to entirely homogeneous lesions in the CCl4 group. Specific hepatic pathological findings (heterogeneous lesions) caused by DMF detected for the first time in humans and animal model, may be significant in the clinical diagnosis of DMF poisoning.

[Research progress on the role of endothelial cell-specific molecular-1 in acute respiratory distress syndrome].

Acute respiratory distress syndrome (ARDS), a common respiratory critical illness with multiple causes, is associated with high mortality. The high degree of heterogeneity may be the reason why it is lack of highly specific and sensitive biological biomarkers. Therefore, it is an urgent need to explore biomarkers, perform phenotypic analysis and establish risk stratification model for diagnosis, prognosis, and treatment of ARDS. Endothelial cells specificity molecular-1 (ESM-1, endocan), is a soluble dermatan sulfate proteoglycan, and be involved in regulating biological behaviors such as cell proliferation, differentiation and migration. Numerous studies have confirmed that ESM-1 is closely related to inflammation, endothelial activation and dysfunction. However, the role of ESM-1 in the initiating and developing process of ARDS is still unclear. To provide a scientific basis for its clinical applications in ARDS, such as early prognosis assessment and timely prevent strategies, this paper focuses on the biological properties and the clinical value of ESM-1 as a potential biomarker for ARDS.

Metabolomics profile in acute respiratory distress syndrome by nuclear magnetic resonance spectroscopy in patients with community-acquired pneumonia.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a challenging clinical problem. Discovering the potential metabolic alterations underlying the ARDS is important to identify novel therapeutic target and improve the prognosis. Serum and urine metabolites can reflect systemic and local changes and could help understanding metabolic characterization of community-acquired pneumonia (CAP) with ARDS. METHODS: Clinical data of patients with suspected CAP at the First Affiliated Hospital of Wenzhou Medical University were collected from May 2020 to February 2021. Consecutive patients with CAP were enrolled and divided into two groups: CAP with and without ARDS groups. 1H nuclear magnetic resonance-based metabolomics analyses of serum and urine samples were performed before and after treatment in CAP with ARDS (n = 43) and CAP without ARDS (n = 45) groups. Differences metabolites were identifed in CAP with ARDS. Furthermore, the receiver operating characteristic (ROC) curve was utilized to identify panels of significant metabolites for evaluating therapeutic effects on CAP with ARDS. The correlation heatmap was analyzed to further display the relationship between metabolites and clinical characteristics. RESULTS: A total of 20 and 42 metabolites were identified in the serum and urine samples, respectively. Serum metabolic changes were mainly involved in energy, lipid, and amino acid metabolisms, while urine metabolic changes were mainly involved in energy metabolism. Elevated levels of serum 3-hydroxybutyrate, lactate, acetone, acetoacetate, and decreased levels of serum leucine, choline, and urine creatine and creatinine were detected in CAP with ARDS relative to CAP without ARDS. Serum metabolites 3-hydroxybutyrate, acetone, acetoacetate, citrate, choline and urine metabolite 1-methylnicotinamide were identified as a potential biomarkers for assessing therapeutic effects on CAP with ARDS, and with AUCs of 0.866 and 0.795, respectively. Moreover, the ROC curve analysis revealed that combined characteristic serum and urine metabolites exhibited a better classification system for assessing therapeutic effects on CAP with ARDS, with a AUC value of 0.952. In addition, differential metabolites strongly correlated with clinical parameters in patients with CAP with ARDS. CONCLUSIONS: Serum- and urine-based metabolomics analyses identified characteristic metabolic alterations in CAP with ARDS and might provide promising circulatory markers for evaluating therapeutic effects on CAP with ARDS.

Renal injury following long-term exposure to carbon disulfide: analysis of a case series.

BACKGROUND: To investigate the clinicopathological characteristics of renal damage caused by long-term exposure to carbon disulfide (CS2) in nine patients. METHODS: All the patients underwent ultrasound-guided renal biopsy. All specimens were examined by light microscopy and immunohistochemistry (IHC). Samples form one patient were further analyzed using transmission electron microscopy. RESULTS: Similar pathological changes were observed in all patients, but the degrees of lesions were different. All cases had moderate to severe nodular mesangial hyperplasia; among these, type "Kimme1stie1-Wi1son" (K-W nodule for short) was observed in four cases, type "K - W nodule" refer to nodular hyperplasia of mesangial membrane like letter K or W. four cases had proliferative extracapillary glomerulonephritis (GN), while there were no concomitant changes in one patient. Besides, six cases had diffuse basement membrane thickening, focal segmental sclerosis or bulbar sclerosis; two cases had diffuse glomerular sclerosis, and one case had focal segmental capillary hyperplasia. Moreover, all patients had renal tubular atrophy/interstitial fibrosis with less to moderate chronic inflammatory cell infiltration, as well as renal arteriosclerosis. IHC showed that the depositions of IgA, IgM, C3d, C4d, C1q and Fib were not specific; while IgG, type III collagen, Fibronectin, Amyloid A, Igκ, Igλ, HBsAg and HBcAg were all negative. CONCLUSION: Diffuse nodular mesangial hyperplasia/sclerosing glomerular nephropathy is characterized by nodular mesangial hyperplasia with type "K-W nodules" formation, which we speculate is a special pathological manifestation of renal damage caused by carbon disulfide (CS2).

Potential therapeutic value of dendritic cells loaded with NY­ESO­1 protein for the immunotherapy of advanced hepatocellular carcinoma.

NY­ESO­1 is one of the most immunogenic cancer-testis (CT) antigens. Cancer vaccine trials based on NY­ESO­1 are currently ongoing. Dendritic cells (DCs) are the most potent antigen-presenting cells. The immune functions of DCs in a number of tumors have been identified; however, the potential therapeutic value of DCs pulsed with NY­ESO­1 in hepatocellular carcinoma (HCC) has not been extensively investigated. The objectives of the present study were to evaluate T cell response following stimulation with DCs pulsed with the recombinant NY­ESO­1 protein (rESO) and to establish a correlation between NY­ESO­1 expression and clinicopathological features in HCC patients. DCs were generated with granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL­4) from human peripheral blood mononuclear cells. A mixed T cell reaction with DCs loaded with recombinant NY­ESO­1 protein (rESO-DCs) was evaluated by MTT assay. T cell responses against HCC cell lines were analyzed by measuring lactate dehydrogenase (LDH) activity. The protein levels of NY­ESO­1 were detected by immunohistochemistry (IHC) in a tissue microarray (TMA) containing 190 HCC samples. NY­ESO­1 transcript abundance was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) in 54 out of the 190 HCC samples. The results revealed that mature DCs were induced and that rESO­DCs significantly stimulated T cell proliferation. The specific lysis of T cells stimulated with rESO­DCs was significantly higher in the NY­ESO­1-positive HCC cells compared with the NY­ESO­1-negative cells and the other controls (p<0.01). NY­ESO­1 was expressed in 15.8% (30/190)of the HCC samples, as shown by IHC and in 24.1% (13/54) of the samples, as shown by RT-PCR. The frequency of NY­ESO­1 expression was significantly higher in HCC patients with portal vein tumor thrombosis (24.6%) compared with those without thrombosis (11.2%, p=0.013). Our data suggest that DCs loaded with NY­ESO­1 protein stimulate antigen-specific T cell responses against HCC cells in vitro. NY­ESO­1 may thus be used as a potential target for immunotherapy in advanced HCC.