Conversion therapy for advanced hepatocellular carcinoma in the era of precision medicine: Current status, challenges and opportunities.

Hepatocellular carcinoma (HCC), the most prevalent malignancy of the digestive tract, is characterized by a high mortality rate and poor prognosis, primarily due to its initial diagnosis at an advanced stage that precludes any surgical intervention. Recent advancements in systemic therapies have significantly improved oncological outcomes for intermediate and advanced-stage HCC, and the combination of locoregional and systemic therapies further facilitates tumor downstaging and increases the likelihood of surgical resectability for initially unresectable cases following conversion therapies. This shift toward high conversion rates with novel, multimodal treatment approaches has become a principal pathway for prolonged survival in patients with advanced HCC. However, the field of conversion therapy for HCC is marked by controversies, including the selection of potential surgical candidates, formulation of conversion therapy regimens, determination of optimal surgical timing, and application of adjuvant therapy post-surgery. Addressing these challenges and refining clinical protocols and research in HCC conversion therapy is essential for setting the groundwork for future advancements in treatment strategies and clinical research. This narrative review comprehensively summarizes the current strategies and clinical experiences in conversion therapy for advanced-stage HCC, emphasizing the unresolved issues and the path forward in the context of precision medicine. This work not only provides a comprehensive overview of the evolving landscape of treatment modalities for conversion therapy but also paves the way for future studies and innovations in this field.

Efficacy of ginseng-based Renshenguben oral solution for cancer-related fatigue among patients with advanced-stage hepatocellular carcinoma: A prospective multicenter cohort study.

BACKGROUND: Cancer-related fatigue (CRF) is a common and debilitating symptom experienced by patients with advanced-stage cancer, especially those undergoing antitumor therapy. This study aimed to evaluate the efficacy and safety of Renshenguben (RSGB) oral solution, a ginseng-based traditional Chinese medicine, in alleviating CRF in patients with advanced hepatocellular carcinoma (HCC) receiving antitumor treatment. METHODS: In this prospective, open-label, controlled, multicenter study, patients with advanced HCC at BCLC stage C and a brief fatigue inventory (BFI) score of ≥ 4 were enrolled. Participants were assigned to the RSGB group (RSGB, 10 mL twice daily) or the control group (with supportive care). Primary and secondary endpoints were the change in multidimensional fatigue inventory (MFI) score, and BFI and functional assessment of cancer therapy-hepatobiliary (FACT-Hep) scores at weeks 4 and 8 after enrollment. Adverse events (AEs) and toxicities were assessed. RESULTS: A total of 409 participants were enrolled, with 206 assigned to the RSGB group. At week 4, there was a trend towards improvement, but the differences were not statistically significant. At week 8, the RSGB group exhibited a significantly lower MFI score (P < 0.05) compared to the control group, indicating improved fatigue levels. Additionally, the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8 (P < 0.05). Subgroup analyses among patients receiving various antitumor treatments showed similar results. Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI, BFI, and FACT-Hep scores at week 8. No serious drug-related AEs or toxicities were observed. CONCLUSIONS: RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period, with no discernible toxicities. These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

Reuse of straw in the form of hydrochar: Balancing the carbon budget and rice production under different irrigation management.

Hydrochar is proposed as a climate-friendly organic fertilizer, but its potential impact on greenhouse gas (GHG) emissions in paddy cultivation is not fully understood. This two-year study compared the impact of exogenous organic carbon (EOC) application (rice straw and hydrochar) on GHG emissions, the net ecosystem carbon budget (NECB), net global warming potential (net GWP), and GHG emission intensity (GHGI) in a rice pot experiment using either flooding irrigation (FI) or controlled irrigation (CI). Compared with FI, CI increased ecosystem respiration by 23 - 44 % and N2O emissions by 85 - 137 % but decreased CH4 emissions by 30 - 58 % (p < 0.05). Since CH4 contributed more to net GWP than N2O, CI reduced net GWP by 16 - 220 %. EOC amendment increased crop yield by 5 - 9 % (p < 0.05). Compared with CK, hydrochar application increased initial GHG emission, net GWP and GHGI in the first year, while in the second year, there was no significant difference in net GWP and GHGI between CI-hydrochar and CK. Compared with straw addition, hydrochar amendment reduced net GWP and GHGI by 20 - 66 % and 21 - 66 %; and exhibited a lower net CO2 emission when considering the energy input during the hydrochar production. These findings suggest that integrated CI-hydrochar practices would be a sustainable and eco-friendly way for organic waste management in rice production as it holds potential to enhance the NECB and SOC sequestration of rice production, while also offsetting the extra carbon emissions from organic inputs.

Migration and Removal of Labile Cadmium Contaminants in Paddy Soils by Electrokinetic Remediation without Changing Soil pH.

Electrokinetic remediation (EKR) is a viable, advanced cleaning strategy that can permanently reduce the toxicity of soil contaminants. However, EKR is prone to causing changes in soil pH. The negative impacts must be minimized if field-scale application is to be realized. In this study, EKR with polarity reversal was used to avoid soil pH polarization and to clean up cadmium (Cd)-contaminated paddy soils. Results showed that Cd desorbed from oxidizable and residual fractions to labile and easily available parts. Soil moisture content above 0.35 g g-1 was conductive to achieving the desirable Cd-migration rate. The exchangeable Cd phase eventually migrated from both ends of that soil compartment towards the intermediate. Moreover, the addition of citric acid at the concentration of 0.1 mol L-1 was an effective enhancement strategy. The methodology enriched Cd contaminants to specific sites. The technology can be used for electrokinetic-assisted phytoremediation during the rice growing period. Hyperaccumulator is planted in the intermediate area to remove the Cd contaminants. On the other hand, Cd removal is achieved in the region close to the electrodes. The present study provides a theoretical basis for in situ remediation. It has a wider significance for field-scale application.

Percutaneous mechanical circulatory support devices in high-risk patients undergoing percutaneous coronary intervention: A meta-analysis of randomized trials.

BACKGROUND: Percutaneous mechanical circulatory support devices (pMCSDs) are increasingly used on the assumption (but without solid proof) that their use will improve prognosis. A meta-analysis was undertaken according to the PRISMA guidelines to evaluate the benefits of pMCSDs in patients undergoing high-risk percutaneous coronary intervention (hr-PCI). METHODS: We searched PubMed, EMbase, Cochrane Library, Clinical Trial.gov, and other databases to identify eligible studies. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated for 30-day and 6-month all-cause mortality rates, reinfarction, and other adverse events using a random effect model. RESULTS: Sixteen randomized controlled trials (RCTs) were included in this study. In the pooled analysis, intra-aortic balloon pump (IABP) was not associated with a decrease in 30-day and 6-month all-cause mortality (RR 1.01 95% CI 0.61-1.66; RR 0.88 95% CI 0.66-1.17), reinfarction (RR 0.89 95% CI 0.69-1.14), stroke/transient ischemic attack (TIA) (RR 1.75 95% CI 0.47-6.42), heart failure (HF) (RR 0.54 95% CI 0.11-2.66), repeat revascularization (RR 0.73 95% CI 0.25-2.10), embolization (RR 3.00 95% CI 0.13-71.61), or arrhythmia (RR 2.81 95% CI 0.30-26.11). Compared with IABP, left ventricular assist devices (LVADs) were not associated with a decrease in 30-day and 6-month all-cause mortality (RR 0.96 95% CI 0.71-1.29; RR 1.23 95% CI 0.88-1.72), reinfarction (RR 0.98 95% CI 0.68-1.42), stroke/TIA (RR 0.45 95% CI 0.1-1.95), acute kidney injury (AKI) (RR 0.83 95% CI 0.38-1.80), or arrhythmia (RR 1.52 95% CI 0.71-3.27), but LVADs were associated with a decrease in repeat revascularization (RR 0.26 95% CI 0.08-0.83). However, LVADs significantly increased the risk of bleeding compared with IABP (RR 2.85 95% CI 1.72-4.73). CONCLUSIONS: Neither LVADs nor IABP improves short or long-term survival in hr-PCI patients. LVADs are more likely to reduce repeat revascularization after PCI, but to increase the risk of bleeding events than IABP.