A Chromatographic Approach for High-Precision Eu Isotope Analysis.

Eu isotopes are promising tracers across various scientific domains such as planetary, earth, and marine science, yet their high-precision analysis has been challenging due to the similar geochemical properties of rare earth elements (REEs). In this study, a novel two-column chromatographic approach was developed utilizing AG50W-X12 and TODGA resins to separate Eu effectively from matrix and interfering elements like Ba, Nd, Sm, and Gd, while ensuring high Eu yields (99.4 ± 0.4%, n = 19) and low blanks (<20 pg). The robustness of this method is evidenced by various rock types and different Eu loading masses. The efficient purification of Eu facilitated the establishment of a high-precision calibration technique with standard-sample bracketing (SSB) and internal normalization (Nd). When a Nu Plasma 1700 multicollector-inductively coupled plasma-mass spectrometry (MC-ICP-MS) instrument was employed, repeated purification and analysis of various Geological Reference Materials (GRMs) confirmed that the long-term external precision of δ153/151Eu is better than 0.04‰ (2 standard deviation (2SD)), which represents a 2-5-fold increase in precision compared to previously reported methods. Additionally, the high-precision Eu isotopic compositions of five GRMs, including basalts, andesite, syenite, and marine sediment, were measured. The high-precision Eu isotope techniques presented herein open up new avenues for Eu isotope geochemistry.

Hangzhou criteria as downstaging criteria in hepatocellular carcinoma before liver transplantation: A multicenter study from China.

BACKGROUND: The downstaging of hepatocellular carcinoma (HCC) has been confirmed to benefit liver transplantation (LT) patients whose tumors are beyond the transplantation criteria. Milan criteria (MC), a tumor size and number-based assessment, is currently used as the endpoint in these patients. However, many studies believe that tumor biological behavior should be added to the evaluation criteria for downstaging efficacy. Hence, this study aimed to explore the feasibility of Hangzhou criteria (HC), which introduced tumor grading and alpha-fetoprotein in addition to tumor size and number, as an endpoint of downstaging. METHODS: We performed a multicenter and retrospective study of 206 patients accepted locoregional therapy (LRT) as downstaging/bridge treatment prior to LT in three centers of China. RESULTS: Recipients were divided into four groups: failed downstaging to the HC (group A, n = 46), successful downstaging to the HC (group B, n = 30), remained within the HC all the time (group C, n = 113), and tumor progressed (group D, n = 17). The 3-year HCC recurrence probabilities of groups B and C were not significantly different (10.3% vs. 11.6%, P = 0.87). The HCC recurrent rate was significantly higher in group A (52.3%) compared with that in group B/C (P < 0.05). Seven patients (7/76, 9.2%) whose tumor exceeded the the HC were successfully downstaged to the MC, and 39.5% (30/76) to the the HC. In group B, 23 patients remained beyond the MC and their survivals were as well as those of patients within the MC. CONCLUSIONS: Compared to the MC, HC downstaging criteria can give more HCC patients access to LT and furthermore, the outcome of these patients is the same as those matching MC downstaging criteria. Hangzhou downstaging criteria therefore is applicable in clinical practice.

The Prognostic Significance of NEK2 in Hepatocellular Carcinoma: Evidence from a Meta-Analysis and Retrospective Cohort Study.

BACKGROUND/AIMS: Numerous studies have shown that NIMA-related kinase 2 (NEK2) expression in hepatocellular carcinoma (HCC) tissue is associated with survival and clinicopathological features; however, the evidence remains inconclusive. Thus, we aimed to further explore the prognostic and clinicopathological significance of NEK2 expression in HCC using a two-part study consisting of a retrospective cohort study and a meta-analysis. METHODS: In the cohort study, NEK2 expression in 206 HCC samples and adjacent normal liver tissues was detected by immunohistochemistry (IHC). Patients were divided into a high NEK2 expression group and a low NEK2 expression group by the median value of the immunohistochemical scores. The Kaplan-Meier method with the log-rank test was used to analyze survival outcomes in the two groups, and multivariate analysis based on Cox proportional hazard regression models was applied to identify independent prognostic factors. In the meta-analysis, eligible studies were searched in PubMed, EMBASE, Web of Science, and CNKI databases. STATA version 12.0 (Stata Corporation, College Station, TX) was used for statistical analyses. RESULTS: The IHC results of our cohort study showed higher NEK2 expression in HCC tissues compared with adjacent normal liver tissues. Multivariate analysis revealed that high NEK2 expression was an independent risk factor for poor overall survival (OS) [hazard ratio (HR) = 1.763; 95% CI, 1.060-2.935; P = 0.029] and disease-free survival (DFS) [hazard ratio (HR) = 1.687; 95% CI, 1.102-2.584; P = 0.016] in HCC patients. A total of 11 studies with 1,698 patients were enrolled in the meta-analysis, consisting of 10 studies from the database search and our cohort study. The pooled results revealed that high NEK2 expression correlated closely with poor OS among HCC patients (HR = 1.47; 95% CI, 1.21-1.80; P < 0.01), and DFS/recurrence-free survival (RFS) (HR = 1.92; 95% CI, 1.41-2.63; P < 0.01). Additionally, our meta-analysis also showed that the proportion of HCC patients with high NEK2 expression was greater in the group with larger tumors (> 5 cm) than in the group with smaller tumors (≤ 5 cm) [odds ratio (OR) = 2.02; 95% CI, 1.13-3.64; P < 0.01). CONCLUSION: Our study demonstrated that high NEK2 expression is a risk factor for poor survival in HCC patients. More prospective, homogeneous, and multiethnic studies are required to validate our findings.

MiR-124 protects human hepatic L02 cells from H2O2-induced apoptosis by targeting Rab38 gene.

BACKGROUND: Hepatic ischemia reperfusion injury (IRI) is an inevitable clinical problem for liver surgeons. Because microRNAs (miRNAs) participate in various hepatic pathophysiological processes, this study aimed to explore the role and potential mechanism of miR-124 in hepatic IRI. METHODS: A liver IRI model was established in rats. The differential expression of miRNAs was detected using microarrays, and the expression of miR-124 was measured by qRT-PCR. A hydrogen peroxide (H2O2)-induced oxidative stress apoptosis model was also established. Cell apoptosis was detected by flow cytometry, and viability was detected by CCK8. The expression of Rab38 was detected by Western blotting and qRT-PCR, and a luciferase reporter assay was used to verify the expression of the miR-124 target gene. RESULTS: The miRNA spectrum changes dramatically after hepatic IRI in rats, and miR-124 is significantly down-regulated after liver IRI. MiR-124 decreases the H2O2-induced apoptosis of human hepatic L02 cells by up-regulating the activation of the AKT pathway. Rab38 is a target gene of miR-124 and is involved in H2O2-induced apoptosis. Interference with the expression of the Rab38 gene can protect hepatic L02 from H2O2-induced apoptosis by increasing the phosphorylation of AKT. These protective effects of miR-124 are attenuated by over-expression of Rab38. CONCLUSIONS: Many miRNAs are involved in hepatic IRI in rats, and miR-124 is significantly decreased in this model. MiR-124 significantly decreases the H2O2-induced apoptosis of human hepatic L02 cells by targeting the Rab38 gene and activating the AKT pathway.

A comprehensive insight into the abundance and community of anammox bacteria in sediments of Hangzhou Bay, China.

A total of 13 surface sediments were collected from Hangzhou Bay (HZB) for an investigation into the distribution and influencing factors of anammox bacterial community. The anammox bacterial 16S rRNA and hzo genes ranged between 2.34 × 105 to 9.22 × 105 copies/g and 3.68 × 105 to 1.70 × 106 copies/g, respectively. The results of high throughput sequencing (HTS) revealed that the obtained OTUs were affiliated with five known genera, named Ca. Scalindua, Ca. Jettenia, Ca. Brocadia, Ca. Kuenenia and Ca. Anammoxoglobus. RDA analysis indicated that salinity, pH, and water depth influenced the anammox bacterial community. Furthermore, network analysis identified Ca. Scalindua as a key genus. Neutral community model (NCM) and modified stochasticity ratio (MST) indicated that the deterministic process dominated the anammox bacterial community assembly. Overall, this study offers a more comprehensive understanding of the abundance and community of anammox bacteria in the sediments of HZB.

Effects of microplastics on cold seep sediment prokaryotic communities.

Cold seep sediments are an important reservoir of microplastics (MPs) whose impact on the structure and function of prokaryotic community is not well understood. In this study, the impact of 0.2% and 1% (w/w) polyethylene (PE), polystyrene (PS), and polypropylene (PP) MPs on the cold seep sediment prokaryotic community was investigated in a 120-day laboratory incubation experiment. The results revealed that exposure to MPs altered sedimentary chemical properties in a type- and concentration-dependent manner. Furthermore, MPs significantly altered the structure of bacterial community, with some MPs degradation-associated bacterial phyla significantly increasing (p < 0.05). However, in the case of archaea, the changes in the structure of microbial community were less pronounced (p > 0.05). Co-occurrence network analysis revealed that the addition of MPs reduced the network complexity, while PICRUSt2 and FAPROTAX analyses suggested that 0.2% PP and 1% PS MPs had the most significant effects on the nitrogen and carbon cycles (p < 0.05). Overall, this study provides new insights into the effects of MPs on the structure and function of microbial communities in cold seep sediments.

Dynamic Changes of Neutrophil-to-Lymphocyte Ratio on Predicting Response of Immune Checkpoint Inhibitors Plus Targeted Therapies for Unresectable Hepatocellular Carcinoma.

Backgrounds and Aims: Multiple regimens of immune checkpoint inhibitors (ICIs) plus targeted therapies are commonly prescribed as first-line treatments for unresectable hepatocellular carcinoma (uHCC). Here, we aimed to investigate the correlation between dynamic changes of neutrophil-to-lymphocyte ratio (NLR) and tumor response to the combination of ICIs and targeted therapies for uHCC. Methods: Sixty-one patients who received ICIs plus targeted therapies for uHCC were enrolled in this retrospective study. The NLR before and at 3-6 weeks after treatments were assessed to calculate the dynamic NLR changes (ΔNLR). Multivariate logistic regression and Cox regression models were used to explore the relationship between dynamic NLR changes and tumor response or progression-free survival (PFS), respectively. Furthermore, we assessed the predictive effect of alpha-fetoprotein (AFP) changes in combination with dynamic NLR changes compared to AFP changes alone. Results: The NLR at 3-6 weeks and ΔNLR after treatments significantly increased in patients who underwent progressive disease (PD), while the baseline NLR showed no significant difference between different tumor responses. Increased NLR and AFP after treatments were both independent predictors of PD (For NLR increase: OR, 2.28; 95% CI, 1.47-3.88, P < 0.001; For AFP increase: OR, 1.46; 95% CI, 1.03-2.17, P = 0.043), and correlated with worse PFS (for NLR increase: HR, 4.08; 95% CI, 1.99-8.36, P < 0.001; for AFP increase: HR, 2.10; 95% CI, 1.04-4.24, P = 0.039). The receiver operating characteristic (ROC) curve and net reclassification index (NRI) showed that the combination of dynamic NLR and AFP changes was better than AFP changes alone on predicting PD (AUC: 0.83 vs 0.68, P = 0.034; NRI: 0.340, P = 0.048) and PFS (AUC: 0.80 vs 0.70, P = 0.166; NRI: 0.431, P = 0.042). Conclusion: Dynamic changes of NLR might be an effective predictor of the therapeutic response to ICIs plus targeted therapies for uHCC.

Response of sedimentary microbial community and antibiotic resistance genes to aged Micro(Nano)plastics exposure under high hydrostatic pressure.

Several studies reported that the presence of microplastics (MPs)/nanoplastics (NPs) in marine environments can alter microbial community and function. Yet, the impact of aged MPs/NPs on deep sea sedimentary ecosystems under high hydrostatic pressure remains insufficiently explored. Herein, the sedimentary microbial community composition, co-occurrence network, assembly, and transfer of antibiotic resistance genes (ARGs) in response to aged MPs/NPs were investigated. Compared with the control, NPs addition significantly reduced bacterial alpha diversity (p < 0.05), whereas MPs showed no significant impact (p > 0.05). Moreover, networks under NPs exhibited decreased complexity than that under MPs and the control, including edges, average degree, and the number of keystone. The assembly of the microbial community was primarily governed by stochastic processes, and aged MPs/NPs increased the importance of stochastic processes. Moreover, exposure to MPs/NPs for one month decreased the abundance of antibiotic resistance genes (ARGs) (from 94.8 to 36.2 TPM), while exposure for four months increased the abundance (from 40.6 to 88.1 TPM), and the shift of ARGs in sediment was driven by both functional modules and microbial community. This study is crucial for understanding the stress imposed by aged MPs/NPs on sedimentary ecosystems under high hydrostatic pressure.

Elevated lead mobility in sediments of a eutrophic drinking water reservoir during spring and summer seasons: Insights from isotopic signatures.

Lead (Pb) pollution in sediments remains a major concern for ecosystem quality due to the robust interaction at the sediment/water interface, particularly in shallow lakes. However, understanding the mechanism behind seasonal fluctuations in Pb mobility in these sediments is lacking. Here, the seasonal variability of Pb concentration and isotopic ratio were investigated in the uppermost sediments of a shallow eutrophic drinking lake located in southeast China. Results reveal a sharp increase in labile Pb concentration during autumn-winter period, reaching ∼ 3-fold higher levels than during the spring-summer seasons. Despite these fluctuations, there was a notable overlap in the Pb isotopic signatures within the labile fraction across four seasons, suggesting that anthropogenic sources are not responsible for the elevated labile Pb concentration in autumn-winter seasons. Instead, the abnormally elevated labile Pb concentration during autumn-winter was probably related to reduction dissolution of Fe/Mn oxides, while declined labile Pb concentration during spring-summer may be attributed to adsorption/precipitation of Fe/Mn oxides. These large seasonal changes imply the importance of considering seasonal effects when conducting sediment sampling. We further propose a solution that using Pb isotopic signatures within the labile fraction instead of the bulk sediment can better reflect the information of anthropogenic Pb sources.

Acceleration of phosphorus weathering under warm climates.

The release of phosphorous (P) via chemical weathering is a vital process that regulates the global cycling of numerous key elements and shapes the size of the Earth's biosphere. It has long been postulated that global climate should theoretically play a prominent role in governing P weathering rates. Yet, there is currently a lack of direct evidence for this relationship based on empirical data at the global scale. Here, using a compilation of temperature and P content data of global surface soils (0 to 30 cm), we demonstrate that P release does enhance at high mean annual surface temperatures. We propose that this amplification of nutrient supply with warming is a critical component of Earth's natural thermostat, and that this relationship likely caused expanded oceanic anoxia during past climate warming events. The potential acceleration of phosphorus loss from soils due to anthropogenic climate warming may pose threats to agricultural production, terrestrial and marine ecosystems, and alter marine redox landscapes.

Adjuvant ICIs Plus Targeted Therapies Reduce HCC Recurrence after Hepatectomy in Patients with High Risk of Recurrence.

BACKGROUND: The high recurrence rate of hepatocellular carcinoma (HCC) after hepatectomy usually results in poor prognosis. To the best of our knowledge, no study has reported the efficacy of immune checkpoint inhibitors (ICIs) plus targeted therapies on preventing HCC recurrence after hepatectomy. Thus, the aim of this study was to investigate the benefits and safety of applying adjuvant ICIs plus targeted therapies after hepatectomy for patients at high risk of HCC recurrence. METHODS: A total of 196 patients with any risk factors for recurrence who underwent hepatectomy for HCC were reviewed in this retrospective study. RESULTS: Compared with the control group (n = 158), ICIs plus targeted therapies (n = 38) had a significantly higher recurrence-free survival (RFS) rate in univariate analysis (HR, 0.46; 95% confidence interval [CI], 0.24-0.90; p = 0.020), multivariate analysis (adjusted HR, 0.62; 95%CI, 0.49-0.79; p < 0.001) and propensity score-matched analysis (HR, 0.35; 95%CI, 0.16-0.75; p = 0.005). Subgroup analyses also showed that postoperative adjuvant ICIs plus targeted therapies might reduce HCC recurrence in patients with the most of risk factors. CONCLUSION: Postoperative adjuvant ICI plus targeted therapies may reduces early HCC recurrence in patients with a high risk of recurrence, and the treatments are well tolerated.

Rare earth elements in soil around coal mining and utilization: Contamination, characteristics, and effect of soil physicochemical properties.

REEs are emerging contaminants, and soils nearby coal and coal ash with high REEs composition are vulnerable to REEs contamination. Besides, coal industry can alter surrounding soil characteristics. However, there is information paucity about REEs contamination and geochemical behaviors along with soil characteristics around coal industrial areas, which are essential for understanding their toxicity and mobilization. The study was conducted in soils surrounding Kriel coal-fired power plant (KCM) and Greenside coal mining in Witbank (GSCM), South Africa. Multivariate statistical analysis, pollution and fractionation indices, and BCR sequential extraction were applied. The ∑REEs in the soils were compared to ∑REEs abundance in the upper earth's crust (UEC), and slightly higher ∑REEs was found in KCM but slightly lower in GSCM. Generally, LREEs are abundant. The soil REEs were normalized using the Post-Archean Australian Shale (PAAS) and Eu and Gd in KCM and Gd in GSCM were >1. Contamination assessment revealed that the soils are slightly to moderately contaminated by REEs. ∑REEs in KCM was significantly correlated with soil particle sizes of 2.00-50.00 µm, Al2O3, Fe2O3, and MnO, while with 2.00-3.00 µm and Al2O3 in GSCM. Fractionation characteristics showed a positive Ce anomaly, with positive linear regressions with Fe2O3 and MnO. In contrast, a negative Eu anomaly was found with positive linear regressions with Al, Ca, and Mg-oxides. Oxidizable fractioned REEs accounted for 32.33% of the ∑REEs in GSCM and 35.85% in KCM, and their high EF suggests enrichment that could be due to coal mining and utilization. Most soil physicochemical properties appear to be negatively correlated with the exchangeable REEs. Overall, the soils are contaminated by REEs and the REEs characteristics are considerably influenced by major elements oxide, U, and Th contents. Therefore, more attention should be paid to REEs contamination and impacts around coal mining and utilization.

Development of a Risk Classifier to Predict Tumor Recurrence and Lenvatinib Benefits in Hepatocellular Carcinoma After Liver Transplantation.

BACKGROUND: Current selection tools were not precise enough to predict recurrence of hepatocellular carcinoma (HCC) and benefit of adjuvant lenvatinib for patients who received liver transplant (LT) for HCC. Thus, we aim at developing a risk classifier to predict recurrence of HCC and benefit of adjuvant Lenvatinib for those who underwent LT for HCC. METHODS: Cox regression model was applied to selected predictors and created the final model in a training cohort of 287 patients who underwent LT for HCC, which was tested in an internal validation cohort of 72 patients by using C-statistic and net classification index (NRI) compared with the following HCC selection criteria: the Milan criteria, the Up-to-7 criteria, and the University of California, San Francisco criteria. RESULTS: We built a Risk Classifier of South China Cohort (RCOSC) based on 4 variables: the maximum diameter plus number of viable tumors, alpha-fetoprotein, microvascular invasion, and highest alanine aminotransferase in 7 days after LT. In validation analyses, our RCOSC showed good predictive performance (C-statistic, 0.866; 95% confidence interval [CI], 0.833-0.899) and had better prognostic value than Milan criteria (NRI, 0.406; P < .001), University of California, San Francisco (NRI, 0.497; P < .001), and Up-to-7 (NRI, 0.527; P < .001). By applying the RCOSC, we were able to accurately categorize patients into high-risk and low-risk groups. Further survival analysis revealed that the patients in the high-risk group might have a better therapeutic response to preventive regimen of lenvatinib after LT for HCC (hazard ratio, 0.38; 95% CI, 0.161-0.871, P = .018). CONCLUSIONS: Our RCOSC presented favorable predictive performance for HCC recurrence. It might be capable of sifting out patients who benefit from adjuvant therapy after LT for HCC, providing a reliable tool for precise clinical decision-making of patients with HCC with LT.

Tenofovir versus entecavir on decreasing risk of HBV-related hepatocellular carcinoma recurrence after liver transplantation.

BACKGROUND: Recent studies have proved that tenofovir disoproxil fumarate (TDF) is associated with a lower risk of hepatocellular carcinoma (HCC) occurrence in chronic hepatitis B (CHB) patients and HCC recurrence in patients who underwent hepatectomy when compared to ETV. However, it is unclear whether TDF and ETV treatment, which are both recommended as first-line antiviral agents to prevent the hepatitis B (HBV) recurrence after liver transplantation (LT), are associated with equivalent prognosis. We aim to compare risk of HCC recurrence and survival of patients recieving TDF or ETV after LT for HBV-related HCC. METHOD: We performed a retrospective study including 316 patients who received treatment with ETV or TDF after LT for HBV-related HCC from 2015 January to 2021 Augest. The Recurrence-free survival (RFS) and overall survival (OS) of TDF and ETV groups were analyzed and compared by propensity score-matched (PSM), multivariable Cox regression analysis, competing risk analysis, sensitivity analyses and subgroup analyses. RESULT: Compared with ETV, TDF therapy was associated with significantly higher RFS rates in the entire cohort (P < 0.01), PSM cohort (P < 0.01) and beyond-Milan cohort (P < 0.01). By multivariable analysis, TDF group was associated with significantly lower rates of HCC recurrence (HR, 0.33; 95%CI, 0.14-0.75; P < 0.01). In subgroup analyses, the similar results were observed in patients with following tumor characteristics: Maximum diameter plus number of viable tumor ≥ 5, with MIV or MAT, AFP at LT ≥ 20 ng/ml, and well or moderate tumor grade. CONCLUSION: Tenofovir decrease risk of HBV-Related Hepatocellular Carcinoma recurrence after liver transplantation compared to Entecavir.

Revealing the response of microbial communities to polyethylene micro(nano)plastics exposure in cold seep sediment.

To date, multiple studies have shown that the accumulation of microplastics (MPs)/nanoplastics (NPs) in the environment may lead to various problems. However, the effects of MPs/NPs on microbial communities and biogeochemical processes, particularly methane metabolism in cold seep sediments, have not been well elucidated. In this study, an indoor microcosm experiment for a period of 120 days exposure of MPs/NPs was conducted. The results showed that MPs/NPs addition did not significantly influence bacterial and archaeal richness in comparison with the control (p > 0.05), whereas higher levels of NPs (1 %, w/w) had a significant adverse effect on bacterial diversity (p < 0.05). Moreover, the bacterial community was more sensitive to the addition of MPs/NPs than the archaea, and Epsilonbacteraeota replaced Proteobacteria as the dominant phylum in the MPs/NPs treatments (except 0.2 % NPs). With respect to the co-occurrence relationships, network analysis showed that the presence of NPs, in comparison with MPs, reduced microbial network complexity. Finally, the presence of MPs/NPs decreased the abundance of mcrA, while promoting the abundance of pmoA. This study will help elucidate the responses of microbial communities to MPs/NPs and evaluate their effects on methane metabolism in cold seep ecosystems.

Early diagenetic control on the enrichment and fractionation of rare earth elements in deep-sea sediments.

The rare earth elements and yttrium (REY) in bioapatite from deep-sea sediments are potential proxies for reconstructing paleoenvironmental conditions. However, the REY enrichment mechanism and the reliability of this tracer remain elusive because of the lack of key information from ambient pore water. Here, we report high-resolution geochemical data for pore water, bottom water, and bioapatite from deep-sea sites in the western Pacific. Our results reveal that the benthic flux of REY from the deep sea is less substantial than from the shallow marine realm, resulting in REY-rich sediment. The depth distribution of REY in pore water is opposite to that of bioapatite, and REY patterns and neodymium isotopic compositions are not uniformly distributed within bioapatite. These results indicate alteration of REY and neodymium isotopic compositions during early diagenesis. Therefore, we infer that REY from bioapatite are not robust recorders of the deep marine environment through Earth's history.

Long-term outcomes of deceased donor liver transplantation in hepatocellular carcinoma patients with portal vein tumor thrombus: A multicenter study.

BACKGROUND: The incidence of portal vein tumor thrombus (PVTT) has been reported to be as high as approximately 10%-40% in patients with hepatocellular carcinoma (HCC). The long-term prognosis of deceased donor liver transplantation (DDLT) in HCC patients with PVTT remains unknown. METHODS: Data of 961 HCC patients who underwent DDLT between 2015 and 2018 in six centers were analyzed. Based on the Milan criteria (MC) and Cheng's classification of PVTT, the patients were divided into 4 groups: within MC, beyond MC without PVTT, type 1 PVTT, and type 2 PVTT groups. RESULTS: 489 (50.9%) were within the MC, 296 (30.8%) beyond the MC but without PVTT, 83 (8.6%) type 1 PVTT, and 93 (9.7%) type 2 PVTT. Kaplan-Meier analysis showed that type 1 or 2 PVTT patients with alpha-fetoprotein (AFP) ≤ 100 ng/mL had overall survival (OS) similar to that of patients within the MC (P = 0.957), and superior OS (P = 0.003 and 0.009) and recurrence-free survival (RFS) (P = 0.038 and <0.001) than those of patients beyond the MC and PVTT patients with AFP > 100 ng/mL. Multivariable Cox-regression analysis identified type 1 and 2 PVTT to be independent risk factor for RFS [hazard ratio (HR) 1.523 95% confidence interval (CI) 1.162-1.997, P = 0.002], but not for OS (HR 1.283, 95%CI 0.922-1.786, P = 0.139). CONCLUSION: HCC patients with type 1 or 2 PVTT may be acceptable candidates for DDLT. To achieve better outcomes, preoperative AFP levels should be seriously considered when selecting patients with PVTT for DDLT.

A Miniature Triaxial Fiber Optic Force Sensor for Flexible Ureteroscopy.

OBJECTIVE: Design and evaluate a miniature triaxial fiber optic sensor which is integrated into the confined space at the tip of a flexible ureteroscope to measure the contact force during ureteroscopy. METHODS: A notched flexure of multilayer continuous beams is deliberately designed to modulate the sensor sensitivity to axial stiffness but not to lateral bending and torsion, and to avoid the crosstalk between axial and lateral forces. Its structure parameters are optimized by the finite element method to meet the needs of miniaturization and performance. A linear decoupled model based on the singular value decomposition algorithm is proposed to accurately compute the forces from the wavelength shifts of fiber Bragg grating. RESULTS: Experimental results show that in the axial direction the sensor has a range of 0-4 N with a resolution of 0.014 N, and in the lateral direction it has a resolution of 0.011 N within the range of -2 N to 2 N, and is able to provide accurate measurement with an error of less than 2%. CONCLUSION: Primary tests show the excellent competence of the sensor to measure the interactive force at the ureteroscope tip and to discriminate objects, validating its reliability and robustness.

Investigating Mechanisms of Response or Resistance to Immune Checkpoint Inhibitors by Analyzing Cell-Cell Communications in Tumors Before and After Programmed Cell Death-1 (PD-1) Targeted Therapy: An Integrative Analysis Using Single-cell RNA and Bulk-RNA Sequencing Data.

Currently, a significant proportion of cancer patients do not benefit from programmed cell death-1 (PD-1)-targeted therapy. Overcoming drug resistance remains a challenge. In this study, single-cell RNA sequencing and bulk RNA sequencing data from samples collected before and after anti-PD-1 therapy were analyzed. Cell-cell interaction analyses were performed to determine the differences between pretreatment responders and nonresponders and the relative differences in changes from pretreatment to posttreatment status between responders and nonresponders to ultimately investigate the specific mechanisms underlying response and resistance to anti-PD-1 therapy. Bulk-RNA sequencing data were used to validate our results. Furthermore, we analyzed the evolutionary trajectory of ligands/receptors in specific cell types in responders and nonresponders. Based on pretreatment data from responders and nonresponders, we identified several different cell-cell interactions, like WNT5A-PTPRK, EGFR-AREG, AXL-GAS6 and ACKR3-CXCL12. Furthermore, relative differences in the changes from pretreatment to posttreatment status between responders and nonresponders existed in SELE-PSGL-1, CXCR3-CCL19, CCL4-SLC7A1, CXCL12-CXCR3, EGFR-AREG, THBS1-a3b1 complex, TNF-TNFRSF1A, TNF-FAS and TNFSF10-TNFRSF10D interactions. In trajectory analyses of tumor-specific exhausted CD8 T cells using ligand/receptor genes, we identified a cluster of T cells that presented a distinct pattern of ligand/receptor expression. They highly expressed suppressive genes like HAVCR2 and KLRC1, cytotoxic genes like GZMB and FASLG and the tissue-residence-related gene CCL5. These cells had increased expression of survival-related and tissue-residence-related genes, like heat shock protein genes and the interleukin-7 receptor (IL-7R), CACYBP and IFITM3 genes, after anti-PD-1 therapy. These results reveal the mechanisms underlying anti-PD-1 therapy response and offer abundant clues for potential strategies to improve immunotherapy.

Nomograms based on clinicopathological factors and inflammatory indicators for prediction of early and late recurrence of hepatocellular carcinoma after surgical resection for patients with chronic hepatitis B.

BACKGROUND: Few studies have focused on the prognostic values of inflammation-related factors for different phases of recurrence in hepatocellular carcinoma (HCC). We aimed to identify the different risk factors for overall, early, and late recurrence, and to establish nomograms based on inflammation-related parameters for predicting the risks of recurrence in a group of HCC patients undergoing hepatectomy. METHODS: We retrospectively enrolled 383 HCC patients with chronic hepatitis B (CHB) who underwent hepatectomy. Univariate and multivariate Cox analyses were conducted to identify independent risk factors for recurrence. Nomograms for overall, early, and late recurrence-free survival (RFS) were established. The discrimination and calibration abilities of the nomograms were evaluated by concordance indexes (C-index), calibration plots, and Kaplan-Meier curves. Finally, receiver operating characteristic (ROC) curves were used to compare the derived nomograms with other existing models. RESULTS: Fibrinogen, lymphocyte-to-monocyte ratio, and S-index inflammation-related factors were independently related to overall and early RFS, but only the S-index correlated with late recurrence. Nomograms with tumor number, diameter, and pathological differentiation for overall and early RFS were established, while nomogram for late recurrence was constructed with tumor number and Child-Pugh grade. The C-indexes for overall, early, and late RFS were 0.679, 0.677, and 0.728, respectively. The calibration plots fit well. The nomograms showed superior discrimination capacities and better performance prediction with larger areas under the curve for recurrence. CONCLUSIONS: The developed nomograms that integrated inflammation-related factors showed high predictive accuracy for overall, early, and late recurrence in HCC patients with CHB after hepatectomy.