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Context. Overuse of N fertiliser in vegetable cropping systems is known to release of nitric and nitrous oxide to the atmosphere in China. Optimisation of N fertilisation regimes has the potential to mitigate NO and [N.sub.2]O emissions from these N-rich systems. Aims. We investigated the effects of different N fertilisation regimes on NO and [N.sub.2]O emissions, and vegetable yields, with particular efforts to estimate annual direct emission factors of NO and [N.sub.2]O under different N fertilisation regimes in greenhouse vegetable fields. Methods. Annual NO and [N.sub.2]O fluxes were taken simultaneously using the static chamber-based method from a greenhouse vegetable system in south-east China with four N fertiliser treatments: (I) no N fertiliser (control); (2) chemical N fertiliser application (CF); (3) organic N fertiliser application (OF); and (4) organic-chemical mixed N fertiliser application (MF). Key results. N fertilisers significantly increased NO and [N.sub.2]O emissions. Direct emission factors of N fertiliser for NO and [N.sub.2]O were the largest for MF, with an average of 0.99% and 0.67%, respectively. Vegetable yields were only significantly enhanced under OF treatment. Conclusions. Relative to the use of chemical N fertiliser, the application of organic-chemical mixed N fertiliser showed not to be effective for mitigating NO and [N.sub.2]O emissions. Instead, sole application of organic N fertiliser was a viable option to enhance vegetable yields but without increasing NO and [N.sub.2]O emissions in greenhouse vegetable systems. Implications. Substituting the use of chemical N fertiliser with organic N fertiliser input could benefitvegetable production but without stimulating NO and [N.sub.2]O emissions from vegetable cropping systems in sub-tropical China. Keywords: emissions factor, greenhouse vegetable field, nitric oxide, nitrous oxide, NO/[N.sub.2]O ratio, organic fertiliser, vegetable yields, WFPS., Introduction Nitric (NO) and nitrous oxide ([N.sub.2]O) are two trace gases that play critical roles in global nitrogen cycle. Both NO and [N.sub.2]O are involved in atmospheric photochemistry processes and [...]

Background: Transarterial therapy (TAT), bevacizumab (Bev), and immune checkpoint inhibitors (ICIs) have individually exhibited efficacy in treating advanced-stage hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of the combination of these three treatments as a neoadjuvant modality in patients with locally advanced HCC. Methods: The primary endpoint is overall survival (OS). The second endpoint is progression free survival (PFS), objective response rate (ORR), pathological response rate and safety. Results: A total of 54 patients received standard systemic therapy comprising Bev combined with ICIs (Bev-ICIs group), 113 patients received direct surgery (Surgery group), and 273 patients received neoadjuvant therapy of TAT combined Bev plus ICIs, among which 79 patients (28.9%) underwent surgical resection after successful tumor downstaging (Neo-surgery group) while the remaining 194 patients (71.1%) received maintenance systemic therapies (Neo-maintenance group). Neoadjuvant following surgery demonstrated a prolonged OS in contrast to direct surgery, with a median OS time not reached in the Neo-surgery group and 30.6 (95% CI: 26.4-34.7) months in the Surgery group (hazard ratio (HR)=0.29, P=0.0058). The median PFS time in the Neo-surgery and Surgery groups stood at 19.2 (95% CI: 16.1-22.2) and 6.3 (95% CI:4.7-8) months, respectively (HR=0.25, P<0.0001). In patients failed to receiving resection after neoadjuvant therapy, the median OS was 22.8 (95% CI: 22.3-23.1) months, whereas that for the standard care population was 19.7 (95% CI: 15.9-24) month (HR=0.53, P=0.023). The median PFS time in Neo-maintenance group and Bev-ICIs groups was 11.2 (95% CI: 10.4-11.9) and 6.4 (95% CI: 4.4-8.5) months (HR=0.60, P=0.024). The ORR and disease control rate (DCR) across all patients received TAT-Bev-ICIs were 38.8% and 89.4%, respectively. Additionally, the pathological complete response (pCR) rate and the major pathological response (MPR) rate were 22.8% and 48.1% in the Neo-surgery group. As for safety, neoadjuvant therapy did not increase the perioperative complications when compared to direct surgery, and demonstrated similar incidences and severity of AEs when compared to the standard systemic therapy. Conclusion: The triple therapy regimen comprising TAT-Bev-ICIs emerged as a promising therapeutic strategy for locally advanced hepatocellular carcinoma (HCC) as a neoadjuvant intervention. [ABSTRACT FROM AUTHOR]

Background: The potential of preoperative CT in the assessment of myeloid immune response and its application in predicting prognosis and immune-checkpoint therapy outcomes in hepatocellular carcinoma (HCC) has not been explored. Methods: A total of 165 patients with pathological slides and multi-phase CT images were included to develop a radiomics signature for predicting the imaging-based myeloid response score (iMRS). Overall survival (OS) and recurrence-free survival (RFS) were assessed according to the iMRS risk group and validated in a surgical resection cohort (n = 98). The complementary advantage of iMRS incorporating significant clinicopathologic factors was investigated by the Cox proportional hazards analysis. Additionally, the iMRS in inferring the benefits of immune checkpoint therapy was explored in an immunotherapy cohort (n = 36). Results: We showed that AUCs of the optimal radiomics signature for iMRS were 0.941 [95% confidence interval (CI), 0.909–0.973] and 0.833 (0.798–0.868) in the training and test cohorts, respectively. High iMRS was associated with poor RFS and OS. The prognostic performance of the Clinical-iMRS nomogram was better than that of a single parameter (p < 0.05), with a 1-, 3-, and 5-year C-index for RFS of 0.729, 0.709, and 0.713 in the training, test, and surgical resection cohorts, respectively. A high iMRS score predicted a higher proportion of objective response (vs. progressive disease or stable disease; odds ratio, 2.311; 95% CI, 1.144–4.672; p = 0.020; AUC, 0.718) in patients treated with anti-PD-1 and PD-L1. Conclusions: iMRS may provide a promising method for predicting local myeloid immune responses in HCC patients, inferring postsurgical prognosis, and evaluating benefits of immune checkpoint therapy. [ABSTRACT FROM AUTHOR]

Background: Systemic chemotherapy (SC) stands the only first-line treatment for advanced intrahepatic cholangiocarcinoma (iCCA) for the past few decades. Immune checkpoint inhibitors (ICIs) have been proved to provide additional benefit in disease control. However, oncological outcome of iCCA remains poor and awaits further improvement with new treatment modalities. Promising results have been observed in lenvatinib plus pembrolizumab (Len-P) as a second-line therapy in iCCA. This study aimed to explore the safety and efficacy of Len-P as a first-line therapy for iCCA patients in real-world clinical practice. Methods: We retrospectively enrolled 133 patients with advanced iCCA who received Len-P or SC between May 2019 and May 2023. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were compared between the two groups. Results: There were 72 patients and 61 patients in the Len-P and SC groups, respectively. The median OS for the Len-P and SC groups was 16.3 and 17.8 months, respectively. The median PFS for the Len-P and SC groups was 8.9 and 11.4 months, respectively. There was no significant difference in ORR and DCR between the Len-P and SC groups (ORR: 22.2% vs. 23%; P=0.92; DCR: 69.4% vs. 77%; P=0.58). Additionally, the overall incidence of AEs was lower in the Len-P group than SC group. Low inflammation-based scores were indicative of favorable outcomes in patients undergoing Len-P therapy. Conclusion: This study demonstrated that Len-P is promising for the treatment of advanced ICC, with highly improved safety. It emerges as a viable treatment alternative for advanced iCCA. Inflammation-based scores show potential utility in identifying individuals likely to benefit from Len-P therapy. [ABSTRACT FROM AUTHOR]

Folate metabolism is involved in the development and progression of various cancers. We investigated the association of single nucleotide polymorphisms (SNP) in folate-metabolising genes and their interactions with serum folate concentrations with overall survival (OS) and liver cancer-specific survival (LCSS) of newly diagnosed hepatocellular carcinoma (HCC) patients. We detected the genotypes of six SNP in three genes related to folate metabolism: methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Cox proportional hazard models were used to calculate multivariable-adjusted hazard ratios (HR) and 95 % CI. This analysis included 970 HCC patients with genotypes of six SNP, and 864 of them had serum folate measurements. During a median follow-up of 722 d, 393 deaths occurred, with 360 attributed to HCC. In the fully-adjusted models, the MTRR rs1801394 polymorphism was significantly associated with OS in additive (per G allele: HR = 0·84, 95 % CI: 0·71, 0·99), co-dominant (AG v. AA: HR = 0·77; 95 % CI: 0·62, 0·96) and dominant (AG + GG v. AA: HR = 0·78; 95 % CI: 0·63, 0·96) models. Carrying increasing numbers of protective alleles was linked to better LCSS (HR10–12 v . 2–6 = 0·70; 95 % CI: 0·49, 1·00) and OS (HR10–12 v . 2–6 = 0·67; 95 % CI: 0·47, 0·95). Furthermore, we observed significant interactions on both multiplicative and additive scales between serum folate levels and MTRR rs1801394 polymorphism. Carrying the variant G allele of the MTRR rs1801394 is associated with better HCC prognosis and may enhance the favourable association between higher serum folate levels and improved survival among HCC patients. [ABSTRACT FROM AUTHOR]

Background: The relative superiority of atezolizumab–bevacizumab versus pembrolizumab-lenvatinib in treatment of unresectable hepatocellular carcinoma (HCC) remains uncertain. This study aims to compare the efficacy of atezolizumab–bevacizumab and pembrolizumab-lenvatinib in first-line treatments for unresectable HCC. Methods: A total of 72 patients receiving pembrolizumab-lenvatinib (PL group) and 92 patients receiving atezolizumab-bevacizumab (AB group) between January 2019 and June 2023 were included in this study. By employing propensity score matching (PSM), we compared the overall survival (OS) and progression-free survival (PFS) between the two groups. Results: After PSM, the 1-, 2-, and 3-year OS rates were 70.4%, 54.5%, and 40.0% in the PL group, and 88.4%, 44.2%, and 44.2% in the AB group, respectively. The 6-, 12-, and 18-month PFS rates were 56.9%, 43.0%, and 32.1% in the PL group, and 74.2%, 40.9%, and 30.7% in the AB group, respectively. No significant differences were observed in both OS (HR, 0.498; 95% CI, 0.217-1.143; P = 0.1) and PFS (HR, 0.913; 95% CI, 0.512-0.1.629; P = 0.758) between the two groups. Through subgroup analysis, we developed a Cirrhosis-Portal vein invasion-ALBI (CPA) score and identified that the AB group exhibited significantly longer OS than the PL group in the CPA high population (HR, 0.219; 95% CI, 0.075–0.637; P = 0.005). The treatment-related adverse events between the PL group and the AB group were comparable. Conclusions: This study suggests that the efficacy of pembrolizumab-lenvatinib and atezolizumab-bevacizumab is comparable in first-line treatment of unresectable HCC, the atezolizumab-bevacizumab combination may confer additional benefits for patients with high CPA scores compared to pembrolizumab-lenvatinib. [ABSTRACT FROM AUTHOR]

Background: Levels of C-reactive protein (CRP) and alpha-fetoprotein (AFP) in immunotherapy (CRAFITY) scores are associated with the prognosis of patients with hepatocellular carcinoma (HCC). This study aimed to explore the efficacy of lenvatinib and pembrolizumab (Len-P) based on the CRAFITY score. Methods: In this study, 228 patients with HCC who received Len-P in Sun Yat-sen University Cancer Center were included. CRAFITY 0 score was defined as AFP level below 100 ng/ml, CRP level below 1 mg/dl, CRAFITY 1 score was defined as AFP level at least 100 ng/ml or CRP level at least 1 mg/dl. CRAFITY 2 scores were defined as AFP levels exceeding 100 ng/ml and CRP levels exceeding 100 ng/ml. The primary outcome was overall survival (OS). The second outcome was tumor response rate. Results: The survival time of CRAFITY 0 is significantly longer than that of CRAFITY 1 and CRAFITY 2 (p =.044). Univariate analysis showed that largest tumor size (HR = 2.149; 95% CI 1.129 - 4.091; p =.02), lymph node metastasis (HR = 2.012; 95% CI 1.132- 3.579; p =.017), and CRAFITY (HR = 0.372; 95% CI 0.168-0.824; p =.015) were important risk determinants of OS in all patients. The results of multivariate analysis show that CRAFITY score is an independent risk factors for OS (HR = 0.719; 95% CI 0.377-1.374; p =.048). The ORR of CRAFITY 0, 1 and 2 scores were 36.4%, 32% and 27.4%, respectively (p =.556). The ORR of intrahepatic lesions by CRAFITY 0, 1 and 2 were 37.9%, 35%, 30.6% (p =.688). Conclusion: CRAFITY score is a good predictor of prognosis in HCC patients receiving Len-P. [ABSTRACT FROM AUTHOR]