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【Objective】 The purpose of this paper is to explore the effects of soil matrix potential (SMP) regulation at different growth stages on the physiological characteristics and yield of spring sown Carthamus tinctorius L. 【Method】 Three SMP thresholds, i.e.,W1(-20 kPa),W2(-30 kPa) and W3(-40 kPa) were set at the elongation period + branching period (A), and elongation period + branching period + flowering period (B), with SMP of -50 kPa at 0.2 m soil depth below the emitter as the CK. At the flowering period, photosynthetic parameters such as the net photosynthetic rate, stomatal conductance, transpiration rate and intercellular CO2 concentration of Carthamus tinctorius L. leaves were measured. At the same time, the physiological indexes such as chlorophyll, soluble protein, malondialdehyde and relative conductivity of Carthamus tinctorius L. leaves were measured. The flower yield of Carthamus tinctorius L. were counted after harvest. 【Result】 The net photosynthetic rate, stomatal conductance, transpiration rate and total chlorophyll content of W1B and W2B treatments reached the maximum, in which W1B increased by 37.1%, 60.0%, 44.6% and 34.1% respectively compared with CK, and W2B increased by 39.6%, 57.7%, 42.8% and 38.8% respectively compared with CK; The soluble protein content of W1B treatment was the largest, which was 43.8% higher than that of CK. The malondialdehyde content and relative conductivity of W1B and W2B were the lowest. The malondialdehyde content and relative conductivity of W1B were 25.0% and 19.0% lower than CK, and W2B was 20.8% and 18.3% lower than CK, respectively; The flower yields of W1B and W2B were the highest, which were 65.8% and 57.1% higher than CK respectively. 【Conclusion】 W1B and W2B treatments had the best photosynthetic characteristics, the highest total chlorophyll content, the lowest malondialdehyde content and relative conductivity, and the highest flower yield. Therefore, maintaining the lower limit of soil matrix potential at -20 kPa or -30 kPa at spring sown Carthamus tinctorius L. elongation period, branching period and flowering period has the highest yield potential. In consideration of water conservation, it is recommended to maintain the lower limit of soil matrix potential at -30 kPa.

Aim: This study aims to investigate α‐fetoprotein (AFP) trajectories for prediction of survival outcomes after hepatic arterial infusion chemotherapy (HAIC) treatment in large hepatocellular carcinoma (HCC). Methods: From May 2014 to June 2020, 889 eligible patients with large HCC underwent HAIC were retrospectively enrolled from five hospitals. A latent class growth mixed (LCGM) model was applied to distinguish potential AFP level dynamic changing trajectories. Inverse‐probability‐of‐treatment weighted (IPTW) analyses were performed to eliminate unmeasured confounders through marginal structural models. Multivariate Cox proportional hazard regression analyses were used to determine the overall survival (OS) in patients with large HCC. Performance of these serum markers for survival prediction was compared by areas under receiver operating characteristic analysis with the Delong test. Results: The median follow‐up time was 23.7 (interquartile range, 3.8–115.3). A total of 1009 patients with large HCC, who underwent HAIC with AFP repeatedly measured 3–10 times, were enrolled in the study. Three distinct trajectories of these serum AFP were identified using the LCGM model: high stable (37.0%; n = 373), low stable (15.7%; n = 159), and sharp‐falling (47.3%; n = 477). Multivariate Cox proportional hazard regression analyses found that ALBI stage 2–3, BCLC‐C stage and high‐stable AFP trajectories were associated with OS. AFP trajectories yield the optimal predictive performance in all risk factors. Conclusions: The AFP trajectories based on longitudinal AFP change showed outstanding performance for predicting survival outcomes after HAIC treatment in large HCC, which provide a potential monitoring tool for improving clinical decision‐making. [ABSTRACT FROM AUTHOR]

Purpose: This study compares the efficacy and safety of lenvatinib and programmed cell death protein (PD)‐1 versus lenvatinib alone for advanced hepatocellular carcinoma (Ad‐HCC) refractory to hepatic arterial infusion chemotherapy (HAIC). Methods: From April 2016 to September 2021, 145 patients with Ad‐HCC refractory to HAIC based on modified Response Evaluation Criteria in Solid Tumors criteria were enrolled by two radiologists and classified into the HAIC‐lenvatinib group (H‐L, n = 87) and HAIC‐lenvatinib‐PD‐1 group (H‐L‐P, n = 58). A propensity score‐matching method was used to reduce selective bias. The overall survival (OS) and postprogression‐free survival (PPS) rates were compared using the Kaplan–Meier method with log‐rank test. Multivariable analyses of independent prognostic factors were evaluated by means of the forward stepwise Cox regression model. Results: After propensity score matching 1:1, the median OS was 43.6 months in the H‐L‐P group and was significantly longer than that (18.9 months) of the H‐L group (p =.009). The median PPS was 35.6 months in the H‐L‐P group and was significantly longer than that (9.4 months) of the H‐L group (p =.009). Multivariate analyses showed that the factors that ‎significantly affected the OS were‎ α‐fetoprotein (hazard ratio [HR], 2.14; 95% CI, 1.26–3.98; p =.006), early response to HAIC (HR, 0.44; 95% CI, 1.20–3.85; p =.009), and H‐L treatment (HR, ‎0.52; 95% CI, 0.30–0.86; p =.012). Modified albumin‐bilirubin grade (HR, 1.32; 95% CI, 1.03–1.70; p =.026), early response to HAIC (HR, 0.44; 95% CI, 0.25–0.77; p =.004), and H‐L (HR, ‎0.47‎; 95% CI, 0.28–0.78; p =.003) significantly affected the PPS. Conclusions: This combination therapy of PD‐1 inhibitors plus lenvatinib has promising survival benefits in the management of patients with Ad‐HCC refractory to HAIC. Plain Language Summary: Lenvatinib plus programmed death 1 inhibitor is an effective and safe postprogression treatment and improved significantly overall survival and postprogression‐free survival compared with lenvatinib alone in patients with advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy. Lenvatinib plus programmed death 1 (PD‐1) inhibitor improved median overall survival (OS) and postprogression‐free survival (PPS) of patients with hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy compared with lenvatinib alone (OS, 18.9 vs 43.6 months, p =.003; PPS, 9.4 vs 35.6 months, p =.002). Lenvatinib plus PD‐1 inhibitor group had a higher postprogression control rate (89.2% [40 of 45 patients] vs 46.5% [21 of 45 patients], p <.001) compared with lenvatinib alone. [ABSTRACT FROM AUTHOR]

Background and aims: Hepatic arterial infusion chemotherapy (HAIC) using the FOLFOX regimen (oxaliplatin plus fluorouracil and leucovorin) is a promising option for large hepatocellular carcinoma (HCC). However, post-HAIC prognosis can vary in different patients due to tumor heterogeneity. Herein, we established two nomogram models to assess the survival prognosis of patients after HAIC combination therapy. Methods: A total of 1082 HCC patients who underwent initial HAIC were enrolled between February 2014 and December 2021. We built two nomogram models for survival prediction: the preoperative nomogram (pre-HAICN) using preoperative clinical data and the postoperative nomogram (post-HAICN) based on pre-HAICN and combination therapy. The two nomogram models were internally validated in one hospital and externally validated in four hospitals. A multivariate Cox proportional hazards model was used to identify risk factors for overall survival (OS). The performance outcomes of all models were compared by area under the receiver operating characteristic curve (AUC) analysis with the DeLong test. Results: Multivariable analysis identified larger tumor size, vascular invasion, metastasis, high albumin–bilirubin grade, and high alpha-fetoprotein as indicators for poor prognosis. With these variables, the pre-HAICN provided three risk strata for OS in the training cohort: low risk (5-year OS, 44.9%), middle risk (5-year OS, 20.6%), and high risk (5-year OS, 4.9%). The discrimination of the three strata was improved significantly in the post-HAICN, which included the above-mentioned factors and number of sessions, combination with immune checkpoint inhibitors, tyrosine kinase inhibitors, and local therapy (AUC, 0.802 versus 0.811, p < 0.001). Conclusions: The nomogram models are essential to identify patients with large HCC suitable for treatment with HAIC combination therapy and may potentially benefit personalized decision-making. Lay summary: Hepatic arterial infusion chemotherapy (HAIC) provides sustained higher concentrations of chemotherapy agents in large hepatocellular carcinoma (HCC) by hepatic intra-arterial, result in better objective response outperformed the intravenous administration. HAIC is significantly correlated with favorable survival outcome and obtains extensive support in the effective and safe treatment of intermediate advanced-stage HCC. In view of the high heterogeneity of HCC, there is no consensus regarding the optimal tool for risk stratification before HAIC alone or HAIC combined with tyrosine kinase inhibitors or immune checkpoint inhibitors treatment in HCC. In this large collaboration, we established two nomogram models to estimate the prognosis and evaluate the survival benefits with different HAIC combination therapy. It could help physicians in decision-making before HAIC and comprehensive treatment for large HCC patients in clinical practice and future trials. [ABSTRACT FROM AUTHOR]

Bladder cancer (BCa) is an increasingly severe clinical and public health issue. Therefore, we aim to investigate BCa susceptibility loci in the Chinese population. In this study, 487 BCa patients and 563 controls were recruited from the First Affiliated Hospital of China Medical University from July 2015 to September 2020. A total of ten single-nucleotide polymorphisms (SNPs) in solute carrier family 15 member 1 (SLC15A1), CWC27 spliceosome associated cyclophilin (CWC27), or UDP glucuronosyltransferase family 1 member A3 (UGT1A3) genes were genotyped. The associations between the candidate SNPs and BCa were analyzed using genotype and haplotype analysis. The results demonstrated that Rs4646227 of SLC15A1 has a significant association with BCa. The patients with CG (OR =2.513, p < 0.05) and GG (OR =2.859, p < 0.05) genotypes had an increasing risk of BCa compared with the CC genotype. For the CWC27 gene, genotypic frequency analysis revealed that the GT or TT genotype of rs2042329 and the CT or TT genotype of rs1870437 were more frequent in BCa patients than those in the control group, indicating that these genotypes were associated with a higher risk of BCa (all p < 0.05). Haplotypes of SLC15A1, UGT1A3, and CWC27 genes found that the C-C-C haplotype of SLC15A1 was associated with a lower risk of BCa while the C-G-C haplotype was associated with a higher risk. For the UGT1A3 gene, a moderate protective effect was observed with the most frequent T-T-C haplotype, and for the CWC27 gene, most of the haplotypes showed no association with BCa, except the G-G-C-T haplotype (order of SNPs: rs2042329-rs7735338-rs1870437-rs2278351, OR =0.81, p =0.038). In sum, this study indicated that rs2042329 and rs1870437 in the CWC27 gene and rs4646227 in the SLC15A1 gene are independent indicators for BCa risk in Chinese people. Further large-scale studies are required to validate these findings. Also, this study provided the theoretical basis for developing new therapeutic drug targeting of BCa. [ABSTRACT FROM AUTHOR]

In this study, different calorimetric and analytical techniques were used to evaluate the thermal behavior of the preparation of 1‐nitronaphthalene through the nitration of naphthalene with mixed acid. Differential scanning calorimetry and adiabatic calorimetry revealed that 1‐nitronaphthalene lacks thermal decomposition characteristics. The results of reaction calorimetry, high‐performance liquid chromatography, and the density function theory method were combined to analyze the reaction mechanism. An expanded Stoessel criticality diagram was developed to evaluate the process safety of the semibatch nitration reaction. The results revealed a higher degree of risk than that obtained when using the traditional Stoessel criticality diagram. Kinetics parameters of the reaction were investigated. [ABSTRACT FROM AUTHOR]

Aims: To compare the effectiveness, safety, and survival outcomes in patients with infiltrative hepatocellular carcinoma (HCC) who underwent hepatic arterial infusion chemotherapy (HAIC) and transarterial chemoembolization (TACE). Methods: A total of 160 patients with infiltrative HCCs who underwent initial TACE (n = 68) and HAIC (n = 92) treatment from January 2016 to March 2020. We applied the propensity score matching (PSM) to adjust for potential imbalances. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were compared between two groups. Multivariate analysis was evaluated through the forward stepwise Cox regression model and β coefficients was applied for the nomogram construction. Results: The median follow-up duration for the study population was 20.8 months. After PSM, the median OS and PFS in the HAIC group were significantly higher than those in the TACE group (OS, 13.3 vs 10.8 months; p = 0.043; PFS, 7.8 vs 4.0 months; p = 0.035) and the ORR and DCR in the HAIC group were significantly higher than those in the TACE group (ORR, 34.8% vs 11.8%; p = 0.001; DCR, 54.3% vs 36.8%; p = 0.028). A nomogram model comprising albumin-bilirubin grade, treatment responses, sessions, and treatment modalities, showed good predictive accuracy and discrimination (training set, concordance index [C-index] of 0.789; validation set, C-index of 0.757), which outperformed other staging systems and conventional indices. Conclusion: HAIC improve significantly survival compared to TACE in patients with infiltrative HCC. A prospective randomized trial is ongoing to confirm this finding. [ABSTRACT FROM AUTHOR]

Immune cells have emerged as key regulators in the occurrence and development of multiple tumor types. However, it is unclear whether immune-related genes (IRGs) and the tumor immune microenvironment can predict prognosis for patients with gastric cancer (GC). The mRNA expression data in GC tissues (n = 368) were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed IRGs in patients with GC were determined using a computational difference algorithm. A prognostic signature was constructed using COX regression and random survival forest (RSF) analyses. In addition, datasets related to "gemcitabine resistance" and "trastuzumab resistance" (GSE58118 and GSE77346) were obtained for GEO database, and DEGs associated with drug-resistance were screened. Then, we analyzed correlations between gene expression and cancer immune infiltrates via Tumor Immune Estimation Resource (TIMER) site. The cBioportal database was used to analyze drug-resistant gene mutation status and survival. One hundred and fifty-five differentially expressed IRGs were screened between GC and normal tissues, and a prognostic signature consisting of four IRGs (NRP1, PPP3R1, IL17RA, and FGF16) was closely related to the overall survival (OS). According to cutoff value of risk score, patients were divided into high-risk and low-risk group. Patients in the high-risk group had shorter OS compared to the low-risk group in both the training (p < 0.0001) and testing sets (p = 0.0021). In addition, we developed a 5-IRGs (LGR6, DKK1, TNFRSF1B, NRP1, and CXCR4) signature which may participate in drug resistance processes in GC. Survival analysis showed that patients with drug-resistant gene mutations had shorter OS (p = 0.0459) and DFS (p < 0.001). We constructed four survival-related IRGs and five IRGs related to drug resistance which may contribute to predict the prognosis of GC. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has received extensive attention as a cancer therapeutic due to its high propensity for tumor targeting with minimal toxicity to healthy tissue. Gastric cancer (GCa) cells show high levels of TRAIL resistance. Epidermal growth factor receptor (EGFR) antagonizes TRAIL-induced apoptosis, but the mechanisms of these effects remain unclear. Our past research confirmed TRAIL-resistant (BGC823 and SGC7901) and TRAIL-sensitive cells (HGC27 and MKN45). miR-429 associated with TRAIL sensitivity was screened using microRNA arrays. The transfection of mimics and inhibitors confirmed that miR-429 negatively correlated with GCa TRAIL resistance. The target gene of miR-429 was identified as PD-L1, which positively correlated with TRAIL resistance through gene silencing and recovery experiments. Using co-immunoprecipitation (co-IP) and proximity ligation assay, we demonstrated that the pro-survival effects of PD-L1 are mediated through the binding and activation of EGFR. Cell viability experiments demonstrated that PD-L1 is key to the maintenance of cell viability in TRAIL-treated cells. This indicated that PD-L1 binds to and participates in EGFR activation through miR-429 regulation to antagonize TRAIL-induced apoptosis. This provides a new theoretical basis for the combination of the EGFR monoclonal antibodies including cetuximab, PD-L1 inhibitors, and human recombinant TRAIL in gastric cancer therapy and can filter patients who are currently sensitive to TRAIL treatment. [ABSTRACT FROM AUTHOR]

Background: An accumulating body of evidence suggests that long non-coding RNAs (lncRNAs) can serve as potential cancer prognostic factors. However, the utility of lncRNA combinations in estimating overall survival (OS) for hepatocellular carcinoma (HCC) remains to be elucidated. This study aimed to construct a powerful lncRNA signature related to the OS for HCC to enhance prognostic accuracy. Methods: The expression patterns of lncRNAs and related clinical data of 371 HCC patients were obtained based on The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs (DElncRNAs) were acquired by comparing tumors with adjacent normal samples. lncRNAs displaying significant association with OS were screened through univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. All cases were classified into the validation or training group at the ratio of 3:7 to validate the constructed lncRNA signature. Data from the Gene Expression Omnibus (GEO) were used for external validation. We conducted real-time polymerase chain reaction (PCR) and assays for Transwell invasion, migration, CCK-8, and colony formation to determine the biological roles of lncRNA. Gene set enrichment analysis (GSEA) of the lncRNA model risk score was also conducted. Results: We identified 1292 DElncRNAs, among which 172 were significant in univariate Cox regression analysis. In the training group (n = 263), LASSO regression analysis confirmed 11 DElncRNAs including AC010547.1, AC010280.2, AC015712.7, GACAT3 (gastric cancer associated transcript 3), AC079466.1, AC089983.1, AC051618.1, AL121721.1, LINC01747, LINC01517, and AC008750.3. The prognostic risk score was calculated, and the constructed risk model showed significant correlation with HCC OS (log-rank P -value of 8.489e-9, hazard ratio of 3.648, 95% confidence interval: 2.238–5.945). The area under the curve (AUC) for this lncRNA model was up to 0.846. This risk model was confirmed in the validation group (n = 108), the entire cohort, and the external GEO dataset (n = 203). GACAT3 was highly expressed in HCC tissues and cell lines. Based on online databases, GACAT3 expression independently affects both OS and disease-free survival in HCC patients. Silencing GACAT3 in vitro significantly suppressed HCC cell proliferation, invasion, and migration. Moreover, pathways related to the lncRNA model risk score were confirmed by GSEA. Conclusion: The lncRNA signature established in this study can be used to predict HCC prognosis, which could provide novel clinical evidence to guide targeted HCC treatment. [ABSTRACT FROM AUTHOR]

Summary: This paper investigates the effects of passenger blockage on smoke flow properties in longitudinally ventilated tunnel fires. A series of numerical simulations were conducted in a 1/5 small‐scale tunnel with the different heat release rates (50‐100 kW), longitudinal ventilation velocities (0.5‐1 m/s), passenger blockage lengths (2‐6 m), and ratios (0.17‐0.267). The typical smoke flow properties in different tunnel fire scenarios are analyzed, and the results show that under the same heat release rate and longitudinal ventilation velocity, the smoke back‐layering length, maximum smoke temperature, and downstream smoke layer height decrease with increasing passenger blockage length or ratio. The Li correlations can well predict the smoke back‐layering length and maximum smoke temperature in tunnel fire scenarios without the passenger blockage. When the passenger blockage exists, the modified local ventilation velocity that takes the blockage length and ratio into account has been proposed to correct the Li correlations. The smoke back‐layering length and maximum smoke temperature with the different blockage lengths and ratios can be predicted by the modified correlations, which are shown to well reproduce the simulation results. [ABSTRACT FROM AUTHOR]