Impact of sarcopenia on postoperative outcomes after hepatectomy in older patients with intrahepatic cholangiocarcinoma: A multicentre cohort study.

BACKGROUND AND AIMS: Sarcopenia is associated with poor prognosis, but its role in older patients with intrahepatic cholangiocarcinoma (ICC) is unclear. We aimed to evaluate the impact of sarcopenia on the prognosis of older patients with ICC undergoing hepatectomy. METHODS: A total of 363 patients with ICC following hepatectomy from 2015 to 2021 were retrospectively reviewed at five institutions. Sarcopenia was evaluated using skeletal muscle index by computed tomography images. Patients were divided into four subgroups according to sarcopenia and age. Postoperative outcomes including complication, overall survival (OS) and recurrence-free survival (RFS) were evaluated. Risk factors were identified through univariate and multivariate Cox regression analyses. RESULTS: 302 patients were included in the analysis. The median age was 63 years and there were 128 patients (42.4%) aged over 65 years. 192 patients (63.6%) were diagnosed with sarcopenia, while 180 patients (59.6%) experienced myosteatosis. Older patients experienced a higher incidence of sarcopenia and myosteatosis, and worse postoperative outcomes than younger patients. In the subgroup of patients with sarcopenia, older patients experienced a significant shorter OS than younger patients, which was not observed in patients without sarcopenia. According to the multivariate Cox regression analysis, lymphatic metastasis (p < .001), blood transfusion (p = .004), low serum albumin (p = .051), sarcopenia (p = .024), and myosteatosis (p = .004) were identified as independent risk factors of OS in older patients, meanwhile tumour size (p = .013) and lymphatic metastasis (p < .001) were independent risk factors of RFS. CONCLUSIONS: Sarcopenia and myosteatosis have a significant adverse impact on postoperative outcomes in older patients with ICC undergoing hepatectomy.

Advanced renal pelvis carcinoma patient with an ERBB2 insertion mutation: a case report.

The prognosis of renal pelvis cancer is poor and therapeutic options are limited, especially for patients with advanced disease. In this report, we present a case of advanced renal pelvis carcinoma in a male patient in his 60s, characterized by an activating mutation in ERBB2. Clinical evaluation resulted in a pathological diagnosis of renal pelvis carcinoma with liver metastasis. Immunohistochemistry staining results suggested that CK, P63, and PAX8 were positively expressed, while Sy, CK7, CK20, S100, PAX8, and HEP1 were negatively expressed. Furthermore, next-generation sequencing results showed an activating mutation in the ERBB2 gene. The patient initially received a trastuzumab-based combination therapy, which led to a significant reduction in ERBB2 mutation frequency and a stable condition after three treatment cycles. However, following continuous treatment for 4 months, the patient developed drug resistance that resulted in disease relapse. Subsequently, the patient received apatinib treatment, but the therapeutic response was not satisfactory. The patient's condition underwent rapid deterioration and he ultimately succumbed to the disease. This case underscores the potential benefit of trastuzumab for treating ERBB2-mutated advanced renal pelvis cancer, but further highlights that overcoming drug resistance remains a crucial challenge for long-term efficacy.

Predicting very early recurrence in intrahepatic cholangiocarcinoma after curative hepatectomy using machine learning radiomics based on CECT: A multi-institutional study.

BACKGROUND: Even after curative resection, the prognosis for patients with intrahepatic cholangiocarcinoma (iCCA) remains disappointing due to the extremely high incidence of postoperative recurrence. METHODS: A total of 280 iCCA patients following curative hepatectomy from three independent institutions were recruited to establish the retrospective multicenter cohort study. The very early recurrence (VER) of iCCA was defined as the appearance of recurrence within 6 months. The 3D tumor region of interest (ROI) derived from contrast-enhanced CT (CECT) was used for radiomics analysis. The independent clinical predictors for VER were histological stage, AJCC stage, and CA199 levels. We implemented K-means clustering algorithm to investigate novel radiomics-based subtypes of iCCA. Six types of machine learning (ML) algorithms were performed for VER prediction, including logistic, random forest (RF), neural network, bayes, support vector machine (SVM), and eXtreme Gradient Boosting (XGBoost). Additionally, six clinical ML (CML) models and six radiomics-clinical ML (RCML) models were developed to predict VER. Predictive performance was internally validated by 10-fold cross-validation in the training cohort, and further evaluated in the external validation cohort. RESULTS: Approximately 30 % of patients with iCCA experienced VER with extremely discouraging outcome (Hazard ratio (HR) = 5.77, 95 % Confidence Interval (CI) = 3.73-8.93, P < 0.001). Two distinct iCCA subtypes based on radiomics features were identified, and subtype 2 harbored a higher proportion of VER (47.62 % Vs 25.53 %) and significant shorter survival time than subtype 1. The average AUC values of the CML and RCML models were 0.744 ± 0.018, and 0.900 ± 0.014 in the training cohort, and 0.769 ± 0.065 and 0.929 ± 0.027 in the external validation cohort, respectively. CONCLUSION: Two radiomics-based iCCA subtypes were identified, and six RCML models were developed to predict VER of iCCA, which can be used as valid tools to guide individualized management in clinical practice.

Clinical and biomarker analyses of sintilimab plus gemcitabine and cisplatin as first-line treatment for patients with advanced biliary tract cancer.

The prognosis of biliary tract cancer (BTC) remains unsatisfactory. This single-arm, phase II clinical trial (ChiCTR2000036652) investigated the efficacy, safety, and predictive biomarkers of sintilimab plus gemcitabine and cisplatin as the first-line treatment for patients with advanced BTCs. The primary endpoint was overall survival (OS). Secondary endpoints included toxicities, progression-free survival (PFS), and objective response rate (ORR); multi-omics biomarkers were assessed as exploratory objective. Thirty patients were enrolled and received treatment, the median OS and PFS were 15.9 months and 5.1 months, the ORR was 36.7%. The most common grade 3 or 4 treatment-related adverse events were thrombocytopenia (33.3%), with no reported deaths nor unexpected safety events. Predefined biomarker analysis indicated that patients with homologous recombination repair pathway gene alterations or loss-of-function mutations in chromatin remodeling genes presented better tumor response and survival outcomes. Furthermore, transcriptome analysis revealed a markedly longer PFS and tumor response were associated with higher expression of a 3-gene effector T cell signature or an 18-gene inflamed T cell signature. Sintilimab plus gemcitabine and cisplatin meets pre-specified endpoints and displays acceptable safety profile, multiomics potential predictive biomarkers are identified and warrant further verification.

Prediction of Response to Lenvatinib Monotherapy for Unresectable Hepatocellular Carcinoma by Machine Learning Radiomics: A Multicenter Cohort Study.

PURPOSE: We aimed to construct machine learning (ML) radiomics models to predict response to lenvatinib monotherapy for unresectable hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: Patients with HCC receiving lenvatinib monotherapy at three institutions were retrospectively identified and assigned to training and external validation cohorts. Tumor response after initiation of lenvatinib was evaluated. Radiomics features were extracted from contrast-enhanced CT images. The K-means clustering algorithm was used to distinguish radiomics-based subtypes. Ten ML radiomics models were constructed and internally validated by 10-fold cross-validation. These models were subsequently verified in an external validation cohort. RESULTS: A total of 109 patients were identified for analysis, namely, 74 in the training cohort and 35 in the external validation cohort. Thirty-two patients showed partial response, 33 showed stable disease, and 44 showed progressive disease. The overall response rate (ORR) was 29.4%, and the disease control rate was 59.6%. A total of 224 radiomics features were extracted, and 25 significant features were identified for further analysis. Two distant radiomics-based subtypes were identified by K-means clustering, and subtype 1 was associated with a higher ORR and longer progression-free survival (PFS). Among the 10 ML algorithms, AutoGluon displayed the highest predictive performance (AUC = 0.97), which was relatively stable in the validation cohort (AUC = 0.93). Kaplan-Meier analysis showed that responders had a better overall survival [HR = 0.21; 95% confidence interval (CI): 0.12-0.36; P < 0.001] and PFS (HR = 0.14; 95% CI: 0.09-0.22; P < 0.001) than nonresponders. CONCLUSIONS: Valuable ML radiomics models were constructed, with favorable performance in predicting the response to lenvatinib monotherapy for unresectable HCC.

A multi-omic approach reveals utility of CD45 expression in prognosis and novel target discovery.

CD45, the leukocyte common antigen, is expressed on almost all cells of the immunological and hematological systems. CD45 expression is related to a variety of diseases, including leukemia and lymphoma. In this study, we analyzed the expression level of CD45 across cancers and evaluated the relationship between its expression and patient prognosis. We further integrated methylation data to explore the differences in CD45 across cancers from a multi-omics perspective. We also analyzed the relationship between CD45 expression and levels of immune cell infiltrates and immune modifiers. Our results revealed the distinct expression characteristics and prognostic value of CD45 across multiple tumors. In addition, we screened drug targets based on the immune index defined by CD45 expression and identified that GPR84 affected the proliferation of tumor cells and was associated with the inflammation caused by immunotherapy. In summary, our findings provide a comprehensive understanding of the role of CD45 in oncogenesis and its prognostic significance across cancers.

Use of miRNA Sequencing to Reveal Hub miRNAs and the Effect of miR-582-3p/SMAD2 in the Progression of Hepatocellular Carcinoma.

Hepatocellular carcinoma is a common tumor with a high fatality rate worldwide, and exploring its pathogenesis and deterioration mechanism is a focus for many researchers. Increasing evidence has shown that miRNAs are involved in the occurrence and progression of a variety of cancers, including hepatocellular carcinoma. Therefore, this study mainly aimed identify key miRNAs related to hepatocellular carcinoma and explore their potential functions and clinical significance. In this study, we performed miRNA sequencing on three pairs of hepatocellular carcinoma tissue samples and screened 26 differentially expressed miRNAs. Then 2 key miRNAs (miR-139-5p and miR-582-3p) were screened by Kaplan-Meier curve analysis, Cox multivariate analysis and qPCR methods. The expression of miR-582-3p was positively correlated with clinicopathological parameters in patients with hepatocellular carcinoma. Subsequently, miRwalk and starbase were used to predict the target genes of key miRNAs, and then the key pairs miR-582-3p/SMAD2 identified by WGCNA, PPI, qPCR and Pearson correlation analysis. Finally, a dual luciferase experiment, the rescue-of-function experiment and qPCR confirmed that miR-582-3p directly targets SMAD2 and regulates the proliferation, migration and invasion of HepG2 cells by targeting SMAD2. At the same time, interference with SMAD2 can influence the effect of miR-582-3p on HepG2 cells. In conclusion, our findings confirm that miR-582-3p is an independent factor for the prognosis of hepatocellular carcinoma patients, and can regulate the progression of hepatocellular carcinoma cells by targeting SMAD2.

In-situ twistable bilayer graphene.

The electrical and optical properties of twisted bilayer graphene (tBLG) depend sensitively on the twist angle. To study the angle dependent properties of the tBLG, currently it is required fabrication of a large number of samples with systematically varied twist angles. Here, we demonstrate the construction of in-situ twistable bilayer graphene, in which the twist angle of the two graphene monolayers can be in-situ tuned continuously in a large range with high precision. The controlled tuning of the twist angle is confirmed by a combination of real-space and spectroscopic characterizations, including atomic force microscopy (AFM) identification of crystal lattice orientation, scanning near-field optical microscopy (SNOM) imaging of superlattice domain walls, and resonant Raman spectroscopy of the largely enhanced G-mode. The developed in-situ twistable homostructure devices enable systematic investigation of the twist angle effects in a single device, thus could largely advance the research of twistronics.

[Source Apportionment and Spatial Distribution Simulation of Heavy Metals in a Typical Petrochemical Industrial City].

Identifying the quantitative source and hazardous areas of heavy metals in soils plays a pivotal role in soil pollution research, and can provide a basis for regional soil risk monitoring and environmental management. For this purpose, a total of 175 samples were collected in topsoils from Linzi, a typical petrochemical industrial city in Shandong Province. Positive matrix factorization (PMF) and factor analysis with non-negative constraints (FA-NNC) receptor models were applied to analyze the sources of the heavy metals. Based on the multivariate statistical simulation methods of min/max autocorrelation factors (MAF) and sequential Gaussian simulation (SGS), the distribution of heavy metal and potential pollution areas were determined. As, Co, Cr, and Mn were mainly affected by natural sources, their concentrations were dominated by the parent materials, and the high-value areas were distributed in the south of the study area. Hg was the most serious pollution element among the 10 heavy metals analyzed in Linzi and originated from atmosphere deposition from industrial emissions and coal combustion, and the highest values were distributed in the northeast of the study area. Cd, Cu, Ni, Pb, and Zn were dominated by natural sources and human activities. The hot-spot areas were mainly concentrated in the middle of the study area. The potentially contaminated areas of Cd and Hg were 580.80 km2 and 666.60 km2, about 85.04% and 97.59% of the total area, and should require more attention. The potential pollution area of most elements was small and scattered across the study area, accounting for less than 1%.

Direct imaging of interlayer-coupled symmetric and antisymmetric plasmon modes in graphene/hBN/graphene heterostructures.

Much of the richness and variety of physics today are based on coupling phenomena where multiple interacting systems hybridize into new ones with completely distinct attributes. Recent development in building van der Waals (vdWs) heterostructures from different 2D materials provides exciting possibilities in realizing novel coupling phenomena in a designable manner. Here, with a graphene/hBN/graphene heterostructure, we report near-field infrared nano-imaging of plasmon-plasmon coupling in two vertically separated graphene layers. Emergent symmetric and anti-symmetric coupling modes are directly observed simultaneously. Coupling and decoupling processes are systematically investigated with experiment, simulation and theory. The reported interlayer plasmon-plasmon coupling could serve as an extra degree of freedom to control light propagation at the deep sub-wavelength scale with low loss and provide exciting opportunities for optical chip integration.

The complete mitochondrial genome of Rhodeus lighti (Cypriniformes: Cyprinidae): sequencing and analysis.

Phylogenetic placement of Rhodeus lighti (R. lighti) remains unresolved. We determined the first complete mitochondrial genome of R. lighti (Cypriniformes: Cyprinidae). The genome is 16,597 bp in length. It consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 2 non-coding regions. The gene composition and order were similar to most of the other vertebrates. The complete mitochondrial genome sequence of R. lighti should contribute towards clarifying the systematics of Rhodeus fishes. The phylogenetic relationships using partitioned Neighbor-Joining tree indicated that (((((Pseudorasbora, Rhodeus) Ctenopharyngodon) (Acheilognathus, Tanakia) Carassius)) Danio rerio). This study will contribute to confirm the phylogenetic status of Rhodeus within family Cyprinidae.

The protective or damaging effect of Tumor necrosis factor-α in acute liver injury is concentration-dependent.

BACKGROUND: Inflammatory cytokine is important in modulating injured diseases. Tumor necrosis factor-α (TNF-α), one of potent inflammatory cytokines, plays a dominant role in host defense reaction. However, the concrete effect of TNF-α on acute liver injury is totally unclear. Here we reported the concrete effect and possible mechanisms of TNF-α on acute liver injury induced by carbon tetrachloride (CCl4). METHODS: SD male rats were equally divided into nine groups. CCl4 (1 ml/kg) was subcutaneously injected into the rats. Enbrel, a TNF-α inhibitor, were intraperitoneally injected at dose of 0, 0.25, 0.5, 1, 2, 4 or 8 mg/kg 15 min before the CCl4 injection. 24 h later, rats were sacrificed. Serum ALT and AST were measured with an autoanalyzer. Serum TNF-α were measured by ELISA. HE staining was used to observe the liver tissue morphology. Hepatocellular apoptosis were tested by immunochemistry and Tunnel kit. Inflammatory factors, involve IL-4, IL-6, IL-8, IL-ß and IFN-γ were detected by RT-PCR. The NF-κB signal pathway and anti-apoptotic genes include Bcl-XL, FHC, XIAP and Bcl-2 were measured by western-blotting and RT-PCR. RESULTS: The change of liver function presented an obvious "V" shape in the whole process of persistently increased Enbrel. As Enbrel was increased gradually from 0 to 1 mg/kg, serum TNF-α were blocked, ALT and AST were gradually decreased as TNF-α as well as the numbers of hepatocellular apoptosis, and were declined to the minimum at 1 mg/kg Enbrel. As Enbrel was increased gradually from 1 to 8 mg/kg, ALT, AST and hepatocellular apoptosis were increased instead, and reached to the maximum at 8 mg/kg Enbrel. HE showed that the seriousness of hepatocellular steatosis was the most at 8 mg/kg Enbrel, and second at 0 mg/kg, the weakest at 1 mg/kg in the acute liver injury. Western-blotting and RT-PCR showed NF-κB, p-IκBα and antiapoptotic genes include Bcl-XL, FHC, XIAP, Bcl-2 were decreased as TNF-α was blocked by increased Enbrel. CONCLUSION: Our results suggested that TNF-α had a dual role in acute liver injury. It was regulated might via the corporate effect of NF-κB signal pawahway and anti-apoptosis. Meanwhile, our findings provide a reference for clinical treatment of acute liver injury.

[Spatial Characteristics and Environmental Risk of Heavy Metals in Typical Gold Mining Area of Shandong Province].

In order to reveal the influence of anthropogenic factors on soil environment quality, a total of seventy-seven samples in topsoils were collected from Jiaojia gold mining area in Shandong province and were determined for Cu, Pb, Zn, Cr contents. Spatial structure, spatial distributions of concentrations and risk probability of heavy metals were analyzed using spatial statistic analysis. The average concentrations of Cu, Pb, Zn and Cr were 19.41 mg·kg-1, 27.32 mg·kg-1, 49.81 mg·kg-1 and 39.27 mg·kg-1, respectively. Pb, Zn and Cr were distributed normally and Cu was distributed normally after logarithm transformation. Semivariance analysis demostrated that Pb could be fitted to exponential model, and Cu, Zn and Cr were fit for spherical model. Nugget coefficents of Cu and Pb were between 0.25 and 0.75, which illustrated middle spatial autocorrelation; Zn and Cr showed the structural variation with nugget values below 0.25. Cu and Pb in the topsoils were distributed dispersedly due to effects of some human factors, whereas contents of Zn and Cr indicated relatively regular distributions and were mainly affected by natural factors. Spatial distributions of the 4 heavy metals were approximately consisitent and the high value areas appeared in the gold mines band. The result of hot spot analysis and indicator kriging interpolation revealed that the relatively high risk areas were located in Jincheng town, the boundary zone of Xinzhuang town and Canzhuang town, while the safe zone was situated in south part of the study area. Pb had higher probability exceeding the threshold and the middle or high environmental risk areas of Pb were distributed widely, which should be paid more attentions.

[Effect of the Runoff-sediment Control of the Xiaolangdi Reservoir on DOC Transport].

The sampling was carried out in Sanmenxia hydrological station, Xiaolangdi hydrological station and Huayuankou hydrological station from November 2011 to October 2012. The impact of the runoff-sediment control of the Xiaolangdi reservoir on DOC transport,was analyzed. The results were as follows. DOC contents in Sanmenxia station, Xiaolangdi station and Huayuankou station were 1.97-2.71 mg-L(-1), 1.87-2.76 mg x L(-1) and 2.07-2.93 mg x L(-1), respectively, during the normal operation period of Xiaolangdi Reservoir and Sanmenxia reservoir, and the DOC content in the three reservoirs had obvious seasonal change. DOC contents in the three stations were 2.14-3.32 mg x L(-1), 2.21-2.84 mg x L(-1) and 2.11-2.84 mg x L(-1), respectively, during the runoff-sediment control, and the DOC content in the sediment-releasing period of reservoir was higher than that in the water-releasing period of reservoir. DOC content had no significant correlation with TSS and flow either during the normal operation or during the water-sediment regulation of the reservoir. But the DOC content had significant correlation with water temperature during the normal operation of the reservoir. DOC flux in Sanmenxia station was similar to that in Xiaolangdi station from November to March. DOC flux in Sanmenxia station was obviously less than that in Xiaolangdi station from April to July. And the DOC flux in Sanmenxia station was much higher than that in Xiaolangdi station from August to October. The result showed that DOC was retained from August to October by Xiaolangdi reservoir and discharged from Xiaolangdi reservoir from April to July. The yearly DOC fluxes were 8.6 x 10(10), 9.0 x 10(10) and 9.7 x 10(10) g respectively in Sanmenxia station, Xiaolangdi station and Huayuankou station. The DOC flux of Sanmenxia station was the highest in September, which accounted for 22.0% of the yearly DOC flux, and the DOC flux of Xiaolangdi station was the highest in June, which accounted for 17.6% of the yearly DOC flux. The DOC flux of Huayuankou station was the highest in July, which accounted for 16.7% of the yearly DOC flux. DOC fluxes during the runoff-sediment regulation accounted for 14.7% and 13.8% of the yearly DOC flux respectively in Xiaolangdi station and Huayuankou station, but the DOC fluxes during the runoff-sediment regulation accounted for only 3.6% of the yearly DOC flux in Sanmenxia station.

A review on hepatocyte nuclear factor-1beta and tumor.

Hepatocyte nuclear factor-1beta (HNF1ß) was initially identified as a liver-specific transcription factor. It is a homeobox transcription factor that functions as a homodimer or heterodimer with HNF1α. HNF1ß plays an important role in organogenesis during embryonic stage, especially of the liver, kidney, and pancreas. Mutations in the HNF1ß gene cause maturity-onset diabetes of the young type 5 (MODY5), renal cysts, genital malformations, and pancreas atrophy. Recently, it has been shown that the expression of HNF1ß is associated with cancer risk in several tumors, including hepatocellular carcinoma, pancreatic carcinoma, renal cancer, ovarian cancer, endometrial cancer, and prostate cancer. HNF1ß also regulates the expression of genes associated with stem/progenitor cells, which indicates that HNF1ß may play an important role in stem cell regulation. In this review, we discuss some of the current developments about HNF1ß and tumor, the relationship between HNF1ß and stem/progenitor cells, and the potential pathogenesis of HNF1ß in various tumors.

Overexpression Of Hepatocyte Nuclear Factor-1beta Predicting Poor Prognosis Is Associated With Biliary Phenotype In Patients With Hepatocellular Carcinoma.

Hepatocyte nuclear factor-1beta (HNF-1B) is involved in the hepatobiliary specification of hepatoblasts to cholangiocytes during liver development, and is strongly expressed throughout adult biliary epithelium. The aim of this study was to examine the expression of HNF-1B in different pathologic subtypes of primary liver cancer, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (ICC), and the relationship between HNF-1B expression, clinicopathological features and prognosis. We retrospectively investigated 2 cohorts of patients, including 183 HCCs and 69 ICCs. The expression of HNF-1B was examined by immunohistochemistry. We found that HNF-1B expression was associated with pathological subtype of primary tumor, and HNF-1B expression in HCC tissue may be associated with the change of phenotype on recurrence. The HNF-1B expression was positively correlated with biliary/HPC (hepatic progenitor cell) markers expression. Further, multivariable analysis showed that HNF-1B expression was an independent prognostic factor for both overall survival and disease-free survival of HCC patients. However, no correlation between HNF-1B expression and survival was found in ICC patients. In summary, HCC with high HNF-1B expression displayed biliary phenotype and tended to show poorer prognosis. HNF-1B-positive malignant cells could be bipotential cells and give rise to both hepatocytic and cholangiocytic lineages during tumorigenesis.