NEDD8-Activating Enzyme Inhibitor MLN4924 Inhibits Both the Tumor Stroma and Angiogenesis in Pancreatic Cancer via Gli1 and REDD1.

PURPOSE: Pancreatic cancer is characterized by a dense desmoplasia stroma, which hinders efficient drug delivery and plays a critical role in tumor progression and metastasis. MLN4924 is a first-in-class NEDD8-activating enzyme inhibitor that exhibits anti-tumor activities toward pancreatic cancer, and given the comprehensive effects that MLN4924 could have, we ask what impact MLN4924 would have on the stroma of pancreatic cancer and its underlying mechanisms. METHODS: Primary pancreatic stellate cells (PSCs) and human HMEC-1 cells were treated with MLN4924 in vitro. The proliferation and extracellular matrix protein levels of PSCs were tested, and their relationship with transcription factor Gli1 in PSCs was investigated. The angiogenic phenotypes of HMEC-1 cells were evaluated using capillary-like tube formation assay, and their relationship with REDD1 in HMEC-1 cells was investigated. RESULTS: In this study, we found that MLN4924 inhibited the proliferation of pancreatic stellate cells and their secretion of collagen and CXCL-1, and the collagen secretion inhibiting effect of MLN4924 was related with transcription factor Gli1. MLN4924 inhibited multiple angiogenic phenotypes of HMEC-1 cells, and mTOR agonist partially relieved the inhibition of MLN4924 on HEMCs. MLN4924 increased the expression of REDD1 and REDD1 knockdown promoted the angiogenic phenotypes of HMEC-1 cells. CONCLUSIONS: Our study suggests that MLN4924 inhibits both the tumor stroma and angiogenesis in pancreatic cancer, and the inhibition effect is related with Gli1 in pancreatic stellate cells and REDD1 in vascular endothelial cells, respectively.

Relationship between Neutrophil-to-HDL Cholesterol Ratio and Mortality in Hospitalized HBV-Associated Decompensated Cirrhosis.

BACKGROUND: Early prognosis prediction in HBV-associated decompensated cirrhosis (HBV-DC) is important to decrease its high mortality. This study aimed to determine the relationship between neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) and 30-day survival in HBV-DC patients. METHODS: This retrospective study involved HBV-DC patients in our hospital from September 2020 to December 2022. The main outcome was 30-day survival. A multivariate analysis was performed to determine whether NHR influenced 30-day survival in the patients, and receiver operating characteristic (ROC) analyses were conducted to calculate the prognostic accuracy of NHR versus Model for End-Stage Liver Disease (MELD) score. RESULTS: In this study, 146 HBV-DC patients were included, and 23 cases (15.8%) died within 30 days. The NHR values differed markedly between non-survivors and survivors, and high NHR was associated with an increased risk of adverse outcomes. On ROC analyses, NHR showed similar predictive accuracy as MELDs for predicting mortality in HBV-DC. CONCLUSIONS: The present study suggests that NHR could be a useful new prognostic tool in HBV-DC patients.

Correlation between Platelet-to-Neutrophil Ratio and Mortality in Patients with HBV-Associated Decompensated Cirrhosis.

BACKGROUND: This study investigated whether platelet-to-neutrophil ratio (PNR) can predict short-term mortality in patients with HBV-associated decompensated cirrhosis (HBV-DeCi). METHODS: We retrospectively analyzed 121 HBV-DeCi patients. Multivariate logistic regression analysis was applied to identify predictors of mortality. Receiver operating characteristic curves were used to determine prognostic accuracy. RESULTS: Thirteen HBV-DeCi patients (10.7%) died at 30 days after admission. PNR was significantly lower in survivors compared with non-survivors and was negatively correlated with Model for End-Stage Liver Disease (MELD) score. Both MELD score and PNR were independent predictors for 30-day mortality. CONCLUSIONS: The present findings suggest that PNR may be a useful biomarker for predicting mortality in HBV-DeCi patients and could have potential for clinical application.

Anemia Predicts Poor Outcomes in Patients with HBV-Related Decompensated Cirrhosis.

BACKGROUND: Anemia is common in patients with severe chronic liver disease, but its role in HBV-related decompensated cirrhosis (DeCi) is still unclear. We therefore aimed to assess the impact of anemia on prognosis in HBV-DeCi patients. METHODS: One hundred thirty-three patients diagnosed with HBV-DeCi were retrospectively collected. RESULTS: A total of 113 (85.0%) patients suffered from anemia in our cohort. The low hemoglobin (Hb) level group exhibited a significantly increased 28-day mortality rate compared with the high Hb group. Hb level was a predictor of 28-day mortality in HBV-DeCi patients. CONCLUSIONS: Reduced Hb levels were associated with unfavorable prognosis in HBV-DeCi patients, and more attention should be paid to anemia in routine clinical assessments of liver cirrhosis.

New prognostic factor for hepatitis B virus-related decompensated cirrhosis: Ratio of monocytes to HDL-cholesterol.

AIM: Hepatitis B virus-related decompensated cirrhosis (HBV-DeCi) has a high mortality rate, and it remains a challenge to predict its outcomes in clinical practice. We aimed to determine the association between monocyte-to-HDL-cholesterol ratio (MHR) and short-term prognosis in HBV-DeCi patients. METHODS: A total of 145 HBV-DeCi patients were enrolled. A multivariate analysis was performed to identify predictors of mortality. The findings were validated by a receiver operating characteristic analysis using the area under the curve (AUC). RESULTS: A total of 20 (13.8%) patients had died 30 days after admission. MHR was markedly increased in the non-survivors compared with the survivors. In the multivariate analysis, MHR was identified as an independent risk factor for mortality, with a significant predictive value (AUC = 0.825; sensitivity, 90.0%; specificity, 62.4%). CONCLUSIONS: Elevated MHR is associated with increased mortality rate in HBV-DeCi patients.

Practical application of Westgard Sigma rules with run size in analytical biochemistry processes in clinical settings.

BACKGROUND: The performance of 18 routine chemical detection methods was evaluated by the sigma (σ) metric, and Westgard Sigma rules with run size were used to establish internal quality control (IQC) standards to reduce patient risks. MATERIALS AND METHODS: External quality assessment (EQA) and internal quality control data from 18 assays in a biochemical laboratory were collected from January to June 2020. The sigma values of each assay were calculated, based on the bias, total error allowable, and coefficient of variation, appropriate quality control rules were selected. According to the quality goal index, the main causes of poor performance were determined to guide quality improvement. RESULTS: At IQC material level 1, seven of the 18 assays achieved five sigma (excellent), and five assays (UA, Crea, AMY, TC and Na) showed world-class performance. At IQC material level 2, 14 of the 18 assays achieved 5 sigma (excellent), and thirteen assays (UA, ALT, CK, Crea, AMY, K, AST, ALP, Na, LDH, Mg, TC and GGT) showed world-class performance. The quality goal index (QGI) was calculated for items with analysis performance <5 sigma, and the main causes of poor performance were determined to guide quality improvement. CONCLUSIONS: Westgard sigma rules with run size are an effective tool for evaluating the performance of biochemical assays. These rules can be used to more simply and intuitively select the quality control strategy of related items and reduce the risk to patients.

Associations between hematological parameters and disease severity in patients with SARS-CoV-2 infection.

BACKGROUND: The emergence and rapid spread of the deadly novel coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a swiftly evolving public health crisis worldwide. SARS-CoV-2 infection is characterized by the development and progression of inflammatory responses. Hematological parameters, such as white blood cells (WBCs) and their subpopulations, red cell distribution width, platelet count, mean platelet volume, plateletcrit, and derived markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio, are established biomarkers of inflammatory responses. We aimed to investigate associations between hematological parameters and disease severity in patients with SARS-CoV-2 infection. METHODS: We retrospectively analyzed data from 68 patients with confirmed SARS-CoV-2 infection. Twenty-two patients had mild illness, and 46 had moderate or severe illness at the time of admission. Univariate and multivariate regression analyses were used to identify correlates of disease severity. The areas under receiver operating characteristic curves were calculated to estimate and compare the predictive values of different diagnostic markers. RESULTS: Mean lymphocyte and monocyte counts were lower while WBC counts, neutrophil counts, NLR, and PLR were higher in patients with severe disease compared with those with mild disease (all P < .01). Univariate analysis revealed that older age, high WBC counts, high neutrophil counts, high NLR, high PLR, low monocyte counts, and low lymphocyte counts were independent correlates of severe illness. Multivariate analysis identified high NLR as the only independent correlate of severe illness. Receiver operating characteristic curve analysis showed that NLR had the highest area under curve of all hematological parameters. CONCLUSION: Among hematological parameters, the NLR showed superior prediction of disease severity in patients with SARS-CoV-2 infection. Thus, the NLR could be a valuable parameter to complement conventional measures for identification of patients at high risk for severe disease.

A tetrahedral DNA nanostructure-decorated electrochemical platform for simple and ultrasensitive EGFR genotyping of plasma ctDNA.

Genotyping of the epidermal growth factor receptor (EGFR) mutation status is of great importance in the screening of appropriate patients with advanced non-small cell lung carcinoma (NSCLC) to receive superior tyrosine kinase inhibitor (TKIs) therapy. Yet conventional assays are generally costly with a relatively long turnaround time for obtaining results, which can lead to a bottleneck for immediately starting TKI therapy in late-staged patients. In this study, we propose an on-site electrochemical platform for sensitive simultaneous genotyping of the two major EGFR mutations (19del and L858R) through plasma ctDNA based on tetrahedral DNA nanostructure decorated screen-printed electrodes (SPE). Linear-after-the-exponential (LATE)-PCR combined with the amplification refractory mutation system (ARMS) was adopted to produce abundant biotin-labeled single-stranded DNA with high amplification efficiency and specificity. Disposable SPE decorated with self-assembled tetrahedral nanostructured DNA probes that showed ordered orientation and good target accessibility enabled the highly efficient hybridization of the specific amplicons through a sandwich-type and quantitatively translated the interfacial hybridization event into electrochemical signals via enzymatic amplification. Taking advantage of the ARMS-based LATE-PCR and the tetrahedral nanostructure-decorated SPE platform, we achieved the accurate detection of around 30 pg DNA of 19del or L858R, or as low as 0.1% of them in the presence of wild-type DNA. Moreover, the EGFR mutation profiles of 13 NSCLC patients we enlisted were accurately genotyped by our electrochemical platform, the results of which were in good agreement with those of commercial genetic detection methods.

Sigma Metrics used to Evaluate the Performance of Internal Quality Control in a Clinical Biochemistry Laboratory.

BACKGROUND: The performance of 17 routine chemical detection methods was evaluated by the Sigma (σ) index, and separate quality control standards were established according to the sigma values of different detection methods. METHODS: The internal quality control (IQC) and external quality assessment (EQA) data of 17 assays in the biochemical laboratory of our hospital were collected from January to June 2019. Referring to the total allowed error (TEa) standards established in the Health Industry Standards of the People's Republic of China (WS/T 403-2012), the sigma metric of each assay was calculated, the performance level for inspection was evaluated, the quality goal index (QGI) was calculated for items with analysis performance < 5 sigma, and the main causes of poor performance were determined to guide quality improvement. RESULTS: For level 1 internal quality control (IQC), five assays (AMY, Crea, UA, TP, and Na) showed a performance of ≥ 6 sigma levels. Five assays (GGT, LDH, ALP, K, and Ca) had a performance lower than 3 sigma. For level 2 IQC, nine assays (ALT, AST, CK, AMY, Crea, UA, TP, Na, and Mg) achieved 6 sigma, and four assays (GGT, LDH, ALP, and K) achieved less than 3 sigma. Among the 12 assays with a sigma value < 5, the precision of 1 assay should be improved first, the accuracy of 6 assays should be improved next, and both the precision and the accuracy of 5 assays should be improved. CONCLUSIONS: The sigma metric is the best tool for evaluating the performance of different test methods. Assays with high sigma values can be evaluated with single-rule quality control, while assays with low values should be evaluated with strict quality control rules.

Evaluation of the neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and red cell distribution width for the prediction of prognosis of patients with hepatitis B virus-related decompensated cirrhosis.

BACKGROUND: The development and progression of hepatitis B virus-related decompensated cirrhosis (DeCi) is associated with inflammatory responses. The monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and red cell distribution width (RDW) are well-known inflammation markers. We aimed to assess the utility of these parameters for predicating the prognosis of patients with HBV-DeCi. METHODS: We retrospectively recruited 174 patients diagnosed with HBV-DeCi. Univariate and multivariate regression models were used to determine risk factors for mortality. Areas under the receiver operating characteristic curves were calculated to estimate and compare the predictive values of the three parameters. Hepatic function was evaluated using the Model for End-Stage Liver Disease (MELD) score. RESULTS: The NLR, RDW, and MLR were found to be significantly higher in patients who did not survive compared with surviving patients. Moreover, these variables were all able to predict early poor outcomes in patients with HBV-DeCi, with NLR exhibiting the highest accuracy. Furthermore, a combination of the NLR and MELD score was a more accurate prognostic marker for predicting mortality than either marker alone in such patients. CONCLUSIONS: Hematological parameters can provide prognostic information for patients with HBV-DeCi. Routine assessment of these parameters at admission may provide valuable data to complement other conventional measures for assessing disease condition in patients with HBV-DeCi.

Platelet-to-white blood cell ratio: A novel and promising prognostic marker for HBV-associated decompensated cirrhosis.

AIM: The present study aimed to investigate associations of the platelet-to-white blood cell ratio (PWR)-a novel hematological indicator of inflammatory responses-with 30-day outcomes in patients with HBV-associated decompensated cirrhosis (HBV-DeCi). METHODS: We recruited 131 patients with HBV-DeCi for this retrospective study and extracted baseline clinical data and laboratory characteristics from medical records. Univariate and multivariate analyses were performed to determine major factors influencing 30-day mortality. Area under the receiver operating characteristic curve analyses was performed to compare the predictive values of prognostic markers. RESULTS: During the 30-day follow-up period, 15 patients died. The PWR was significantly different between nonsurvivors and survivors. Lower PWR was found to be associated with an increased risk of mortality, and PWR was found to be an independent predictor of mortality in patients with HBV-DeCi. CONCLUSIONS: Our results demonstrate that low PWR may be a predictor of poor prognosis in patients with HBV-DeCi, and this factor may be a useful supplement to standard approaches to enable effective management of these patients.

The C-Reactive Protein/Albumin Ratio as a Predictor of Mortality in Patients with HBV-Related Decompensated Cirrhosis.

BACKGROUND: The C-reactive protein to albumin ratio (CAR) is a novel inflammation index that has recently been used as a marker for poor prognosis or mortality in various patient groups. This study aimed to evaluate the association between the CAR and 30-day mortality in patients with hepatitis B virus-related decompensated cirrhosis (HBV-DeCi). METHODS: This was a retrospective cohort study of 113 patients who had been diagnosed with HBV-DeCi. Univariate and multivariate regression models were used to determine risk factors for mortality. RESULTS: The CAR was observed to be significantly higher in the non-surviving patients compared to the surviving patients. Moreover, the CAR was positively correlated with the model for end-stage liver disease (MELD) score and Child-Pugh score. In multivariate analysis, the CAR and the MELD score were independent prognostic factors for HBV-DeCi patients. CONCLUSIONS: A high CAR value at admission can serve as an independent predictor of 1-month mortality in patients with HBV-DeCi.

Serum Insulin-Like Growth Factor-1 (IGF-1): a Novel Prognostic Factor for Early Recurrence of Hepatocellular Carcinoma (HCC).

BACKGROUND: Early recurrence within 1 year is the leading cause of early death in patients with hepatocellular carcinoma (HCC) after liver resection. Circulating levels of insulin-like growth factor-1 (IGF-1) reflect the liver function and prognosis of patients with HCC. In the present study, we aimed to evaluate whether baseline and dynamic changes in serum IGF-1 were associated with early recurrence in patients with HCC who underwent liver resection. METHODS: A total of 144 HCC patients who underwent liver resection were included in this study. Circulating levels of IGF-1 and other tumor-related indexes were collected during the perioperative period. Univariate and multivariate analyses were used to examine potential risk factors for early recurrence. Receiver operating characteristic (ROC) was used to determine the cutoff value of preoperative IGF-1 and compare the predictive use of independent risk factors for early recurrence alone or in combination. RESULTS: Early recurrence was observed in 50 (34.7%) patients in a median follow-up period of 17.9 months. Serum IGF-1 levels achieved complete recovery within 30 days after hepatectomy. Multivariate analysis indicated that microscopic vascular invasion (MVI) (HR = 2.479, p = 0.002), preoperative low circulating IGF-1 level (HR = 0.276, p < 0.001), and delayed recovery of IGF-1 level at 30 days after liver resection (ᇞIGF-1 < 0) (HR = 2.293, p = 0.005) were three independent risk factors for early recurrence in HCC patients. When three independent risk factors were combined, the area under the ROC curves (AUCs) was significantly increased to 0.803 and markedly larger than those for the individual risk factors (p < 0.001). CONCLUSIONS: A low preoperative circulating IGF-1 level, negative ᇞIGF-1, and MVI were significantly associated with an increased risk of early recurrence in HCC patients, and applying the three independent risk factors together may improve the prognosis of early recurrence in patients with HCC after liver resection.

Association between Serum Sialic Acid Levels and Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study.

BACKGROUND: To assess the association between serum sialic acid (SA) levels and nonalcoholic fatty liver disease (NAFLD) in a Chinese population. METHODS: A cross-sectional study was performed among 3,898 Chinese who took their annual health examination. Serum SA levels and other clinical and laboratory parameters were measured. RESULTS: A total of 18.11% fulfilled the diagnostic criteria of NAFLD. NAFLD subjects with/without metabolic syndrome (MS) had significantly higher serum SA levels than those without NAFLD. Serum SA levels were significantly and positively correlated with components of MS (body mass index, systolic blood pressure, diastolic blood pressure, triglyceride and fasting plasma glucose) in the NAFLD group. Stepwise logistic regression analysis showed that SA levels were significantly associated with the risk factor for NAFLD. Serum SA levels were negatively correlated with the FIB-4 score, and lower serum SA levels were independent factors predicting advanced fibrosis in subjects with NAFLD. CONCLUSIONS: Our results showed a significant association between serum SA levels and NAFLD.

Evaluation of an automated microplate technique in the Galileo system for ABO and Rh(D) blood grouping.

BACKGROUND: A number of automated devices for pretransfusion testing have recently become available. This study evaluated the Immucor Galileo System, a fully automated device based on the microplate hemagglutination technique for ABO/Rh (D) determinations. METHODS: Routine ABO/Rh typing tests were performed on 13,045 samples using the Immucor automated instruments. Manual tube method was used to resolve ABO forward and reverse grouping discrepancies. D-negative test results were investigated and confirmed manually by the indirect antiglobulin test (IAT). RESULTS: The system rejected 70 tests for sample inadequacy. 87 samples were read as "No-type-determined" due to forward and reverse grouping discrepancies. 25 tests gave these results because of sample hemolysis. After further tests, we found 34 tests were caused by weakened RBC antibodies, 5 tests were attributable to weak A and/or B antigens, 4 tests were due to mixed-field reactions, and 8 tests had high titer cold agglutinin with blood qualifications which react only at temperatures below 34 degrees C. In the remaining 11 cases, irregular RBC antibodies were identified in 9 samples (seven anti-M and two anti-P) and two subgroups were identified in 2 samples (one A1 and one A2) by a reference laboratory. As for D typing, 2 weak D+ samples missed by automated systems gave negative results, but weak-positive reactions were observed in the IAT. CONCLUSIONS: The Immucor Galileo System is reliable and suited for ABO and D blood groups, some reasons may cause a discrepancy in ABO/D typing using a fully automated system. It is suggested that standardization of sample collection may improve the performance of the fully automated system.

Monocyte chemotactic protein-1 as possible prognostic markers of the efficacy of antiviral treatment in chronic hepatitis C.

BACKGROUND/AIMS: Antiviral therapy with interferon and ribavirin had been proved to be effective in Hepatitis C treatment. However, the valuable markers for monitoring the efficacy of antiviral therapy are required clinically. The present study aimed to evaluate the association between pretreatment levels of Monocyte chemoattractant protein-1 levels (MCP-1) and the virological response in treated patients with chronic hepatitis C infection. METHODOLOGY: Concentrations of MCP-1 in serum were determined in 165 patients with chronic hepatitis C (CHC) treated with interferon and ribavirin by enzyme linked immunosorbent assay before and 48 weeks after cessation of therapy. RESULTS: Pretreatment MCP-1 levels in patients with sustained virological response (SVR) were significantly lower than in non-responders (Non-SVR) (220.2 +/- 31.7 vs. 305.6 +/- 50.7 pg/mL, p = 0.009) and MCP-1 significantly decreased in patients with SVR (form 220.2 +/- 31.7 pg/mL to 140.2 +/- 26.7 pg/mL; p <0.01) but not in Non-SVR (form 305.6 +/- 50.7 pg/mL to 286.6 +/- 41.9 pg/mL; p = 0.17) after 48 weeks of treatment. By multivariate analysis, non-1 genotype was independent predictors of SVR in all patients. When multivariate analysis was restricted to patients with non-1 genotype, only pretreatment MCP-1 levels were identified as predictive factors of SVR. CONCLUSIONS: MCP-1 may be a prognostic marker of the efficacy of antiviral therapy in CHC patients.

Changes of ammonia levels in patients with acute on chronic liver failure treated by plasma exchange.

BACKGROUND/AIMS: Acute on chronic liver failure (AoCLF) is associated with a high mortality rate. Plasma exchange (PE) is useful to bridge AoCLF patients to liver transplantation. The aim of this study was to assess the effects of PE on plasma ammonia levels (PAL) in AoCLF patients. METHODOLOGY: Seventy patients with AoCLF in 2 groups (PE plus standard medical treatment group, n = 32; and standard medical treatment group, n = 38) were enrolled in study. PAL was detected on admission and on days 7, 14, 21, and 30 during hospitalization. RESULTS: All AoCLF patients showed PAL more than the upper limit of the normal range. More dramatic decreased in the PE survivors (form 116.8 +/- 36.3 to 44.8 +/- 16.3, p < 0.01) than the medical survivors (form 105.7 +/- 30.2 to 57.1 +/- 20.3, p < 0.05) after 30 days of treatment. Furthermore, PAL after medical treatment were still higher than those of PE treatment in the survivors (57.1 +/- 20.3 vs. 44.8 +/- 16.3, p < 0.05). Among the non-survivors in the medical group, PAL remained at high levels throughout the examination period. Importantly, an increased PAL associated with high mortality and reduced survival time of AoCLF patients. CONCLUSIONS: Ammonia may be important in the pathogenesis of the AoCLF and PE may represent a reliable hepatic support device for AoCLF.

Elevated neutrophil-to-hemoglobin ratio as an indicator of poor survival in hepatitis B virus-related decompensated cirrhosis.

Aim: Our goal was to explore the prognostic value of the neutrophil-to-hemoglobin ratio (NHR) in HBV-related decompensated cirrhosis (HBV-DC) patients. Methods: 172 HBV-DC patients were enrolled. Multivariate analyses were used to identify risk factors influencing 30-day mortality. Results: The 30-day mortality was 12.8% (22/172). nonsurvivors exhibited a higher NHR than survivors. On multivariate analysis, NHR and model for end-stage liver disease (MELD) score were the only independent predictors of mortality. Notably, the predictive capabilities of NHR were found to be comparable to those of the MELD score. Conclusion: High NHR was associated with poor prognosis in HBV-DC patients, and NHR can serve as an effective and readily available indicator for the prediction of mortality in these patients.

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Red cell distribution width-to-albumin ratio is a predictor of survival in hepatitis B virus-associated decompensated cirrhosis.

OBJECTIVE: The aim of this study was to ascertain whether red cell distribution width-to-albumin ratio (RAR) is associated with survival in hepatitis B virus (HBV)-associated decompensated cirrhosis (DC) patients. METHODS: A cohort of 167 patients with confirmed HBV-DC was enrolled in our study. Demographic characteristics and laboratory data were obtained. The main endpoint was mortality at 30 days. The receiver operating characteristic curve and multivariable regression analysis were used to assess the power of RAR for predicting prognosis. RESULTS: Mortality at 30 days was 11.4% (19/167). The RAR levels were higher in the nonsurvivors than the survivors, and elevated RAR levels were clearly associated with poor prognosis. Moreover, the predictive powers of RAR and Model for End-Stage Liver Disease score were not obviously different. CONCLUSION: Our data indicate that RAR is a novel potential prognostic biomarker of mortality in HBV-DC.

Poor clinical outcomes and immunoevasive contexture in CD161+CD8+ T cells barren human pancreatic cancer.

BACKGROUND: The role of CD161 expression on CD8+ T cells in tumor immunology has been explored in a few studies, and the clinical significance of CD161+CD8+ T cells in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study seeks to clarify the prognostic value and molecular characteristics linked to CD161+CD8+ T cell infiltration in PDAC. METHODS: This study included 186 patients with confirmed PDAC histology after radical resection. CD161+CD8+ T cell infiltration was assessed using immunofluorescence staining on tumor microarrays. Flow cytometry and single-cell RNA sequencing were used to evaluate their functional status. RESULTS: We observed significant associations between tumor-infiltrating CD161+CD8+ T cells and clinicopathological factors, such as tumor differentiation, perineural invasion, and serum CA19-9 levels. Patients with higher tumor-infiltrating CD161+CD8+ T cell levels had longer overall survival (OS) and recurrence-free survival (RFS) than those with lower levels. Multivariable analysis confirmed tumor-infiltrating CD161+CD8+ T cell as an independent prognostic indicator for both OS and RFS. Notably, a combination of tumor-infiltrating CD161+CD8+ T cell and CA19-9 levels showed a superior power for survival prediction, and patients with low tumor-infiltrating CD161+CD8+ T cell and high CA19-9 levels had the worst survival. Furthermore, lower tumor-infiltrating CD161+CD8+ T cells were associated with a better response to adjuvant chemotherapy. Finally, we identified tumor-infiltrating CD161+CD8+ T cells as a unique subtype of responsive CD8+ T cells characterized by increased levels of cytotoxic cytokines and immune checkpoint molecules. CONCLUSION: CD161+CD8+ T cells exhibit elevated levels of both cytotoxic and immune-checkpoint molecules, indicating as a potential and attractive target for immunotherapy. The tumor-infiltrating CD161+CD8+ T cell is a valuable and promising predictor for survival and therapeutic response to adjuvant chemotherapy in PDAC. Further research is warranted to validate its role in the risk stratification and optimization of therapeutic strategies.