Research progress of flexible pressure sensor based on MXene materials.

Flexible pressure sensors overcome the limitations of traditional rigid sensors on the surface of the measured object, demonstrating broad application prospects in fields such as sports health and vital sign monitoring due to their excellent flexibility and comfort in contact with the body. MXene, as a two-dimensional material, possesses excellent conductivity and abundant surface functional groups. Simultaneously, MXene's unique layered structure and large specific surface area offer a wealth of possibilities for preparing sensing elements in combination with other materials. This article reviews the preparation methods of MXene materials and their performance indicators as sensing elements, discusses the controllable preparation methods of MXene materials and the impact of their physical and chemical properties on their functions, elaborates on the pressure sensing mechanism and evaluation mechanism of MXene materials. Starting from the four specific application directions: aerogel/hydrogel, ink printing, thin film/electronic skin, and fiber fabric, we introduce the research progress of MXene flexible pressure sensors from an overall perspective. Finally, a summary and outlook for developing MXene flexible pressure sensors are provided.

From Conversion to Resection for Unresectable Hepatocellular Carcinoma: A Review of the Latest Strategies.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, accounting for the majority of primary liver cancer cases. Liver resection is the preferred curative method for early-stage HCC. However, up to 80-85% of patients have already missed the opportunity of radical surgery due to tumor advances at the time of consultation. Conversion therapies are a series of medications and treatments for initially inoperable patients. For early-stage unresectable HCC (uHCC) patients, conversion therapies are designed to meet surgical requirements by increasing the volume of the residual liver. Meanwhile, for advanced cases, conversion therapies strive for tumor shrinkage and down-staging, creating the opportunity for liver resection or liver transplantation. This review summarizes the latest advances in conversion therapies and highlights their potential for improving the survival benefit of patients with uHCC.

Immunotherapy combination with regorafenib for refractory hepatocellular carcinoma: A real-world study.

PURPOSE: To compare the efficacy and safety of immunotherapy plus regorafenib versus regorafenib only in patients with pretreated hepatocellular carcinoma (HCC). METHODS: Immunotherapy plus regorafenib or regorafenib alone was analyzed in patients with advanced HCC with documented tumor progression on front-line therapy. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and treatment-related adverse events (TRAEs) were assessed. RESULTS: Of the 125 patients enrolled in this study, 50 patients received combination (pCOM) treatment as front-line treatment, and 60 patients received monotherapy (pMONO) as front-line treatment. In the pCOM cohort, median OS was significantly longer with for patients regorafenib plus immunotherapy than regorafenib alone treatment (15.0 vs. 2.0 months; P = 0.035). The DCR numerically increased in the regorafenib plus immunotherapy treatment in both cohorts (40.6 % vs. 22.2 %, 72.7 % vs. 54.7 %, respectively). There were no differences in PFS with regorafenib according to whether or not regorafenib was combined with immunotherapy in the pCOM and pMONO cohorts (PFS, P = 0.17, P = 0.91, respectively). Regarding the number of TRAEs occurred, regorafenib plus immunotherapy group was comparable to regorafenib group in the pCOM cohort (65.6 % vs. 72.2 %). In the pMONO cohort, TRAEs occurred in fewer patients receiving regorafenib than regorafenib plus immunotherapy (69.8 % vs. 95.5 %). CONCLUSIONS: Immunotherapy plus regorafenib may significantly improve clinical outcomes and have a manageable safety profile compared with regorafenib monotherapy in advanced HCC after front-line therapy failure. The efficacy of combination therapy needs to be validated in prospective studies with large samples.

Concave octopus-like PtCu nanoframe mediated photo-electro Fenton catalysis for fast organic dyestuff elimination.

In this work, a photo-electro Fenton catalytic nanoplatform based on concave octopus-like PtCu nanoframes was fabricated for organic dyestuff degradation. The electrochemical oxidation reaction was performed to generate hydrogen peroxide (H2O2) on the interface of PtCu nanoframes via a promising electro-Fenton process for on-demand aqueous remediation.

Three-dimensional bio-printing of primary human hepatocellular carcinoma for personalized medicine.

Hepatocellular carcinoma (HCC) is one of the most lethal tumors worldwide. This study aims to address the lack of faithful and available in vitro models for patient-specific drug screening for HCC. We recently established a novel modeling system using three-dimensional (3D) bioprinting technology and constructed hepatorganoids with HepaRG cells, which retain the liver function and prolong the survival of mice with liver failure after abdominal transplantation. Here we extend this modeling system to establish individualized model for hepatocellular carcinoma. HCC specimens were obtained from six patients after surgery. Primary HCC cells were isolated and mixed with gelatin and sodium alginate to form the bioink for printing. Patient-derived three-dimensional bio-printed HCC (3DP-HCC) models were successfully established afterward and grew well during long-term culture. These models retained the features of parental HCCs, including stable expression of the biomarker, stable maintenances of the genetic alterations and expression profiles. 3DP-HCC models are capable of displaying the results of drug screening intuitively and quantitatively. In conclusion, 3DP-HCC models are faithful in vitro models that are reliable in long-term culture and able to predict patient-specific drugs for personalized treatment.

γ-glutamyl transferase-to-platelet ratio based nomogram predicting overall survival of gallbladder carcinoma.

BACKGROUND: Gallbladder carcinoma (GBC) carries a poor prognosis and requires a prediction method. Gamma-glutamyl transferase-to-platelet ratio (GPR) is a recently reported cancer prognostic factor. Although the mechanism for the relationship between GPR and poor cancer prognosis remains unclear, studies have demonstrated the clinical effect of both gamma-glutamyl transferase and platelet count on GBC and related gallbladder diseases. AIM: To assess the prognostic value of GPR and to design a prognostic nomogram for GBC. METHODS: The analysis involved 130 GBC patients who underwent surgery at Peking Union Medical College Hospital from December 2003 to April 2017. The patients were stratified into a high- or low-GPR group. The predictive ability of GPR was evaluated by Kaplan-Meier analysis and a Cox regression model. We developed a nomogram based on GPR, which we verified using calibration curves. The nomogram and other prognosis prediction models were compared using time-dependent receiver operating characteristic curves and the concordance index. RESULTS: Patients in the high-GPR group had a higher risk of jaundice, were older, and had higher carbohydrate antigen 19-9 levels and worse postoperative outcomes. Univariate analysis revealed that GPR, age, body mass index, tumor-node-metastasis (TNM) stage, jaundice, cancer cell differentiation degree, and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were related to overall survival (OS). Multivariate analysis confirmed that GPR, body mass index, age, and TNM stage were independent predictors of poor OS. Calibration curves were highly consistent with actual observations. Comparisons of time-dependent receiver operating characteristic curves and the concordance index showed advantages for the nomogram over TNM staging. CONCLUSION: GPR is an independent predictor of GBC prognosis, and nomogram-integrated GPR is a promising predictive model for OS in GBC.

Bioprinting of patient-derived in vitro intrahepatic cholangiocarcinoma tumor model: establishment, evaluation and anti-cancer drug testing.

Towards the development of in vivo-mimicking tumor model for extensive study of tumorigenesis and establishment of personalized therapy, patient-derived primary tumor cells were employed in this work for three-dimensional (3D) bioprinting. Intrahepatic cholangiocarcinoma cells isolated from patient were bioprinted using a composite hydrogel system of gelatin-alginate-MatrigelTM into pre-designed grid architecture. ICC cells were observed to process a colony forming ability with high survival rate and active proliferation. Expression levels of tumor markers, cancer stem cell markers, matrix metalloproteinase protein, index of tumor fibrosis, index of liver function, and epithelial-mesenchymal transition regulatory proteins confirmed the development of the invasive and metastatic phenotype of the intrahepatic cholangiocarcinoma cells in the 3D printed tumor microenvironment. Similar results were obtained in anti-cancer drug resistance of the intrahepatic cholangiocarcinoma cells in the 3D bioprinted construct that demonstrated stem-like properties, which suggested the promising potential of current 3D printed tumor model in the development of personalized therapy, especially for discovery of more conducive targeted drugs.

Application of a 3D Bioprinted Hepatocellular Carcinoma Cell Model in Antitumor Drug Research.

The existing in vitro models for antitumor drug screening have great limitations. Many compounds that inhibit 2D cultured cells do not exhibit the same pharmacological effects in vivo, thereby wasting human and material resources as well as time during drug development. Therefore, developing new models is critical. The 3D bioprinting technology has greater advantages in constructing human tissue compared with sandwich culture and organoid construction. Here, we used 3D bioprinting technology to construct a 3D model with HepG2 cells (3DP-HepG2). The biological activities of the model were evaluated by immunofluorescence, real-time quantitative PCR, and transcriptome sequencing. Compared with the traditional 2D cultured tumor cells (2D-HepG2), 3DP-HepG2 showed significantly improved expression of tumor-related genes, including ALB, AFP, CD133, IL-8, EpCAM, CD24, and ß-TGF genes. Transcriptome sequencing analysis revealed large differences in gene expression between 3DP-HepG2 and 2D-HepG2, especially genes related to hepatocyte function and tumor. We also compared the effects of antitumor drugs in 3DP-HepG2 and 2D-HepG2, and found that the large differences in drug resistance genes between the models may cause differences in the drugs' pharmacodynamics.

Albumin binding function is a novel biomarker for early liver damage and disease progression in non-alcoholic fatty liver disease.

PURPOSE: Indicators to assess early liver damage and disease progression in nonalcoholic fatty liver disease (NAFLD) remain unsatisfactory. Albumin binding function has been reported to be an early indicator of liver damage in hepatitis and liver cirrhosis. However, its role in NAFLD patients is unknown. METHODS: An age/sex-matched, case-control study was performed. Albumin-binding capacity (ABiC) and albumin metal ion binding ability, assessed by ischemia modified albumin (IMA), were measured. Correlation analysis was performed to assess the association of albumin binding function with liver function enzymes and noninvasive liver fibrosis markers. RESULTS: A total of 80 NAFLD patients and 41 healthy controls were included. Albumin binding function was significantly lower in NAFLD (ABiC: 196.00%, p < 0.001; IMA transformed (IMAT): 0.461, p < 0.001; and IMAT/albumin: 0.947 × 10-2, p < 0.001) than controls (ABiC: 211.00%; IMAT: 0.575; and IMAT/albumin: 1.206 × 10-2). Albumin binding function was also found to be significantly different among healthy participants and different severity groups of NAFLD (p < 0.001). Besides, albumin binding function showed positive correlation with BMI (ABiC: r = -0.247, p = 0.011; IMAT: r = -0.243, p = 0.013; IMAT/albumin: r = -0.254, p = 0.009) and FIB-4 index (ABiC: r = 0.230, p = 0.029). The ROC curve suggested that albumin binding function combined with BMI and triglyceride may predict the presence of NAFLD (area under ROC (AUROC) = 0.935, p < 0.001). CONCLUSION: Our findings suggest albumin binding function is a novel biomarker for early liver damage and disease progression in NAFLD.

The Clinicopathological and Prognostic Value of PD-L1 Expression in Cholangiocarcinoma: A Meta-Analysis.

Background: Recently, blockade of immune checkpoint has emerged as one of the most potential treatments for solid tumors. Programmed cell death ligand 1(PD-L1), a member of the B7 family of molecules, plays a crucial role in tumor immunobiology. However, the prognostic significance of PD-L1 in cholangiocarcinoma (CCA) patients remains controversial. This study aimed to inquire into the prognostic and clinicopathological significance of PD-L1 in CCA via a meta-analysis. Methods: We searched PubMed, the Cochrane Library, Embase, Web of Science and Google Scholar up to April 2019, regardless of the region or language, for studies on the correlation between clinicopathology/prognosis and PD-L1 in patients with CCA. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to investigate the prognostic significance of PD-L1 expression in cholangiocarcinoma. The odds ratios (ORs) were also determined to explore the association between PD-L1 expression and clinicopathological features. Results: Our meta-analysis included 11 studies with 1,066 patients. The meta-analysis of these studies indicated a trend that high PD-L1 expression indicated a poor OS, but the result was not statistically significant (HR = 1.62, 95% CI [0.98-2.68], p = 0.063). For DFS, although the pooled result is not statistically significant, it trends toward being significant that high PD-L1 expression indicated improved DFS (HR = 0.80, 95% CI [0.62, 1.04], p = 0.092). In subgroup analyses, the results were not consistent across the subgroups that were divided based on the publication year (before 2018: HR = 1.92, 95% CI [1.34-2.75], p < 0.001; after 2018: HR = 1.42, 95% CI [0.70-2.89], p = 0.335). Moreover, PD-L1 expression in TCs significantly correlated with the AJCC TNM stage of CCA (OR = 0.52, 95% CI [0.27, 0.99], p = 0.09). Conclusion: Our meta-analyses revealed that PD-L1 expressed in TCs was significantly correlated with the AJCC TNM stage of CCA. Based on the included studies, we found that PD-L1 indeed expressed in both TCs and ICs in CCA patients, raising the possibility of the use of anti-PD-1/PD-L1 therapy for CCA patients. In contrast, expression of PD-L1 did not seem to be associated with patient outcome in our study. The prognostic role of PD-L1 in CCA demands further investigation.