Identification of DNA repair gene signature and potential molecular subtypes in hepatocellular carcinoma.

DNA repair is a critical factor in tumor progression as it impacts tumor mutational burden, genome stability, PD-L1 expression, immunotherapy response, and tumor-infiltrating lymphocytes (TILs). In this study, we present a prognostic model for hepatocellular carcinoma (HCC) that utilizes genes related to the DNA damage response (DDR). Patients were stratified based on their risk score, and groups with lower risk scores demonstrated better survival rates compared to those with higher risk scores. The prognostic model's accuracy in predicting 1-, 3-, and 5-year survival rates for HCC patients was analyzed using receiver operator curve analysis (ROC). Results showed good accuracy in predicting survival rates. Additionally, we evaluated the prognostic model's potential as an independent factor for HCC prognosis, along with tumor stage. Furthermore, nomogram was employed to determine the overall survival year of patients with HCC based on this independent factor. Gene set enrichment analysis (GSEA) revealed that in the high-risk group, apoptosis, cell cycle, MAPK, mTOR, and WNT cascades were highly enriched. We used training and validation datasets to identify potential molecular subtypes of HCC based on the expression of DDR genes. The two subtypes differed in terms of checkpoint receptors for immunity and immune cell filtration capacity.Collectively, our study identified potential biomarkers of HCC prognosis, providing novel insights into the molecular mechanisms underlying HCC.

Bedside Blood Glucose Monitoring in Critically Ill Patients: Comparison Between Arterial and Capillary Glucose.

BACKGROUND: Critically ill patients are at high risk of hypoglycemia and are particularly vulnerable to unrecognized hypoglycemia. Close blood glucose monitoring is therefore crucial. There are several options to conduct frequent blood glucose measurement and a number of conditions in intensive care unit patients may affect the accuracy of blood glucose measurement. The aim of the study was to compare the accuracy of capillary glucose by bedside glucometer with arterial samples by bedside glucometer and arterial samples by blood gas analyzer in critically ill patients through a prospective case-control study. MATERIALS AND METHODS: Arterial and capillary samples from 60 patients were taken simultaneously and were tested immediately at the bedside. Results of the paired measurements were compared and expressed as a correlation coefficient. RESULTS: Capillary glucose in the study group and control group were 9.73 ± 2.28mmol/L and 8.9 ± 1.86mmol/L, respectively; mean arterial glucose measured by glucometer in the study group and control group were 9.25 ± 2.05mmol/L and 8.4 ± 1.89mmol/L, respectively; and mean arterial glucose measured by blood gas analyzer in the study group and control group were 8.41 ± 1.9mmol/L and 8.24 ± 1.5mmol/L, respectively. Correlation between capillary values and arterial values measured by glucometer was less in the study group (r = 0.936, P < 0.001 and r = 0.973, P < 0.001). Correlation between capillary values measured by glucometer and arterial values measured by blood gas analyzer was also less in the study group (r = 0.897, P = 0.001 and r = 0.964, P < 0.001). CONCLUSIONS: Capillary blood glucose monitoring is reliable only in a selected group of critically ill patients.

A Hemophagocytic Lymphohistiocytosis Patient that Presented with Unilateral Panuveitis.

PURPOSE: To describe a case of hemophagocytic lymphohistiocytosis (HLH) with ocular changes prior to the systemic changes. METHODS: A 53-year-old man presented with the chief complaint of decreased vision in his right eye. The patient was examined by ocular examination, slit lamp examination, optical coherence tomography, laboratory examination, abdominal ultrasound, and bone marrow biopsy. RESULTS: Ocular examination revealed uveitis OD and optical coherence tomography revealed macular edema OD. Laboratory examination demonstrated cytopenia in two cell lines, hypofibrinogenemia, and elevated serum ferritin. Abdominal ultrasound findings indicated hepatosplenomegaly. The bone marrow biopsy specimen demonstrated histiocytes and significant hemophagocytosis, leading to a diagnosis of HLH. CONCLUSION: Ophthalmic manifestation can be the first sign of HLH and progress to fatal systemic changes.

[Unfractionated heparin inhibits lipopolysaccharide-induced expression of chemokines in human endothelial cells through nuclear factor-ΚB signaling pathway].

OBJECTIVE: To determine the effect of unfractionated heparin (UFH) on lipopolysaccharide (LPS)-induced expression of chemokines and nuclear factor-ΚB (NF-ΚB) signaling pathway. METHODS: Human pulmonary microvascular endothelial cells (HPMECs) were cultured in vitro, and the cells between passages 3 and 5 were used in the experiments. The cells were divided into control group, LPS challenge group, 1 kU/L or 10 kU/L UFH+LPS group, and NF-ΚB inhibitor N-tosyl-L-lysyl chloromethyl-ketone (TLCK) group (TLCK+LPS group). HPMECs in LPS challenge group were treated with 10 mg/L LPS. UFH pretreatment with different dosages groups were treated with 1 kU/L or 10 kU/L UFH 15 minutes before LPS challenge. Cells in the TLCK+LPS group were treated with 10 µmol/L of TLCK 30 minutes before the addition of LPS, and HPMECs in control group were treated with an equal volume of phosphate-buffered saline (PBS) instead. The cells were harvested 1 hour after LPS challenge, and the nuclear translocation of NF-ΚB was determined by immunofluorescence assay to detect the effect of UFH on NF-ΚB activation. The levels of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in cell culture supernatants were determined by enzyme linked immunosorbent assay (ELISA) 3 hours and 6 hours after LPS challenge to detect the effect of UFH on LPS induced expression of chemokines and its mechanism of effect on NF-ΚB signaling pathway in HPMECs. RESULTS: (1) In the control group, NF-ΚB was mostly located in the cytosol as shown by immunofluorescence. Treatment of HPMECs with LPS significantly increased the translocation of NF-ΚB from the cytosol to nucleus. UFH suppressed LPS-induced NF-ΚB activation both in 1 kU/L and 10 kU/L dosages, and 10 kU/L UFH gave even better results. (2) Compared with control group, the levels of IL-8 and MCP-1 in the supernatants in LPS challenge group were significantly increased at 3 hours and 6 hours after LPS challenge [IL-8 (ng/L): 387.1±26.4 vs. 23.8±8.1 at 3 hours, 645.5±69.6 vs. 125.7±18.7 at 6 hours; MCP-1 (ng/L): 3 654.9±467.9 vs. 721.6±61.3 at 3 hours, 8 178.5±792.6 vs. 1 324.7±148.7 at 6 hours, all P < 0.05]. Compared with that of LPS challenge group, in 1 kU/L and 10 kU/L UFH pretreatment groups, the levels of IL-8 and MCP-1 were significantly decreased [IL-8 (ng/L): 315.3±24.8, 275.8±31.1 vs. 387.1±26.4 at 3 hours, 557.8±43.3, 496.9±38.7 vs. 645.5±69.6 at 6 hours; MCP-1 (ng/L): 2 924.1±267.9, 2 668.3±522.6 vs. 3 654.9±467.9 at 3 hours, 7 121.7±557.2, 6 563.9±576.4 vs. 8 178.5±792.6 at 6 hours, all P < 0.05]. The results indicated that 10 kU/L UFH yielded better results. However, inhibition study using the known NF-ΚB inhibitor TLCK could decrease LPS-induced increase in IL-8 and MCP-1 levels [IL-8 (ng/L): 162.4±21.3 vs. 387.1±26.4 at 3 hours, 274.1±22.6 vs. 645.5±69.6 at 6 hours; MCP-1 (ng/L): 1 478.2±138.5 vs. 3 654.9±467.9 at 3 hours; 3 667.6±259.4 vs. 8 178.5±792.6 at 6 hours, all P < 0.05]. CONCLUSIONS: The levels of IL-8 and MCP-1 were increased obviously in LPS treated HPMECs. UFH might suppress LPS-activated NF-ΚB signaling pathway, contributing to the inhibitory effects of chemokines in HPMECs.