Dual-responsive probe and DNA interstrand crosslink precursor target the unique redox status of cancer cells.

Elevated GSH and H2O2 in cancer cells is sometimes doubted due to their contrary reactivities. Here, we construct a dual-responsive fluorescent probe to confirm the conclusion, and employ this to exploit a redox-inducible DNA interstrand crosslink (ICL) precursor. It crosslinks DNA upon activation by GSH and H2O2, affording an alternative dual-responsive strategy.

Effects of adjuvant huaier granule therapy on survival rate of patients with hepatocellular carcinoma.

Objective: Clinical trials have reported that Huaier granule inhibits the recurrence of hepatocellular carcinoma (HCC) after resection. However, its efficacy in patients at different clinical stages of HCC remains unknown. We investigated the effects of Huaier granule on the 3-year overall survival (OS) rate of patients at different clinical stages. Design: This cohort study included 826 patients with HCC, screened between January 2015 and December 2019. The patients were divided into Huaier (n = 174) and control groups (n = 652), and the 3-year OS rates were compared between the two groups. To eliminate bias caused by confounding factors, propensity score matching (PSM) was performed. We used the Kaplan-Meier method to estimate OS rate and tested the difference using the log-rank test. Results: Multivariable regression analysis revealed that Huaier therapy was an independent protective factor for 3-year survival rate. After PSM (1:2), the Huaier and control groups comprised 170 and 340 patients, respectively. The 3-year OS rate was remarkably higher in the Huaier group than in the control group (adjusted hazard ratio [aHR]: 0.36; 95% confidence interval: 0.26-0.49; p < 0.001). The aHR for Huaier use for 3-12, 12-24, and >24 months was 0.48, 0.23, and 0.16, respectively, indicating a dose-response pattern. For the 3-12-, 12-24-, and >24-month groups, the 3-year OS rate was 54.1%, 68.6%, and 90.4%, respectively. Multivariate stratified analysis confirmed that the mortality risk in Huaier users was lower than that in non-Huaier users in most subgroups. Conclusion: Adjuvant Huaier therapy improved the OS rate in patients with HCC. However, these findings require further verification through prospective clinical studies.

Neutrophil-to-high-density-lipoprotein-cholesterol ratio and mortality among patients with hepatocellular carcinoma.

Background: Inflammatory responses and lipid metabolism disorders contribute to the development and prognosis of hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic value of lipid-related inflammatory parameters in patients with HCC. Methods: From January 2010 to June 2017, we enrolled 1,639 patients with HCC at Beijing Ditan Hospital. Multivariate Cox regression analysis and area under the receiver operating characteristic (AUC) analysis were used to evaluate and compare the predictability and reliability of high-density lipoprotein cholesterol (HDL-C), neutrophil-to-HDL-C ratio (NHR), monocyte-to-HDL-C ratio (MHR), and lymphocyte-to-HDL-C ratio (LHR) values. A restricted cubic spline was used to explore the association between the NHR and 3-year mortality in patients with HCC. Differences in survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test. The results were validated in an internal cohort between July 2017 and October 2019 (n = 373). Results: After adjusting for confounding variables, NHR was independently associated with 3-year mortality, both as a continuous and categorical variable (both p < 0.05). The correlation between the mortality and the MHR and LHR was not statistically significant. The NHR showed a suitable prognostic value (AUC at 3 years: 0.740), similar to that of the Model for End-stage Liver Disease (MELD) (AUC at 3 years: 0.761). In the validation cohort, the AUC of the NHR was 0.734 at 3 years. The optimal cut-off values of NHR and MELD were 3.5 and 9, respectively. The 3-year survival rates in the low- (NHR < 3.5 and MELD <9) and high-risk (NHR ≥ 3.5 and MELD ≥9) groups were 81.8 and 19.4%, respectively, in the training cohort, and 84.6 and 27.5%, respectively, in the validation cohort. Conclusion: Baseline NHR is a promising prognostic parameter for mortality in patients with HCC and patients with NHR ≥ 3.5 and MELD ≥9 have a high mortality rate.

Development of a nomogram to predict the risk of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis on antivirals.

Objective: Patients with compensated hepatitis B-related cirrhosis receiving antivirals are at the risk of hepatocellular carcinoma (HCC). This study aimed to develop and validate a nomogram for predicting the incidence of HCC in patients with hepatitis-B related cirrhosis. Design: A total of 632 patients with compensated hepatitis-B related cirrhosis treated with entecavir or tenofovir between August 2010 and July 2018 were enrolled. Cox regression analysis was used to identify independent risk factors for HCC and a nomogram was developed using these factors. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analyses were used to evaluate the nomogram performance. The results were validated in an external cohort (n = 324). Results: In the multivariate analysis, age per 10 years, neutrophil-lymphocyte ratio > 1.6, and platelet count < 86×109/L were independent predictors of HCC occurrence. A nomogram was developed to predict HCC risk using these three factors (ranging from 0 to 20). The nomogram showed better performance (AUC: 0.83) than that of the established models (all P < 0.05). The 3-year cumulative HCC incidences in the low- (scores < 4), medium- (4-10), and high-risk (> 10) subgroups were 0.7%, 4.3%, and 17.7%, respectively, in the derivation cohort, and 1.2%, 3.9%, and 17.8%, respectively, in the validation cohort. Conclusion: The nomogram showed good discrimination and calibration in estimating HCC risk in patients with hepatitis-B related cirrhosis on antivirals. High-risk patients with a score > 10 points require close surveillance.

Association between probiotic therapy and the risk of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis.

Objective: Probiotics may offer cancer-prevention benefits, based on experimental investigation results. This study aimed to determine the potential association between probiotics and hepatocellular carcinoma (HCC) in patients with hepatitis B-related cirrhosis (HBC) receiving antiviral therapy. Design: This retrospective study included 1267 patients with HBC treated with entecavir or tenofovir between January 2013 and December 2017. The risk of developing HCC was compared between two cohorts of 449 probiotic users (taking a cumulative defined daily doses [cDDD] of ≥ 28) and 818 non-probiotic users (< 28 cDDD). To eliminate the bias caused by confounding factors, propensity score matching (PSM) was used. Results: On multivariate regression analysis, probiotic consumption was an independent protective factor for HCC occurrence. After PSM, the incidence of HCC was significantly lower in the probiotic users than that in the nonusers (adjusted hazard ratio [aHR]: 0.70, 95% confidence interval: 0.59-0.83, P < 0.001). The aHRs for probiotics with 28-89, 90-180, and >180 cDDD were 0.58, 0.28, and 0.12, respectively, indicating a dose-response pattern. In 28-89, 90-180, and >180 cDDD, the 3-year cumulative incidence of HCC was 8.7%, 4.7%, and 3.0%, respectively. A multivariate stratified analysis confirmed that the administration of probiotics could help patients. Conclusion: Adjuvant probiotic therapy may reduce the risk of HCC in patients receiving antiviral medication for HBC. However, further clinical research is required to confirm these findings.