A multi-institutional study to predict the benefits of DEB-TACE and molecular targeted agent sequential therapy in unresectable hepatocellular carcinoma using a radiological-clinical nomogram.

OBJECTIVE: Exploring the efficacy of a Radiological-Clinical (Rad-Clinical) model in predicting prognosis of unresectable hepatocellular carcinoma (HCC) patients after drug eluting beads transcatheter arterial chemoembolization (DEB-TACE) to optimize the targeted sequential treatment. METHODS: In this retrospective analysis, we included 202 patients with unresectable HCC who received DEB-TACE treatment in 17 institutions from June 2018 to December 2022. Progression-free survival (PFS)-related radiomics features were computationally extracted from HCC patients to build a radiological signature (Rad-signature) model with least absolute shrinkage and selection operator regression. A Rad-Clinical model for postoperative PFS was further constructed according to the Rad-signature and clinical variables by Cox regression analysis. It was presented as a nomogram and evaluated by receiver operating characteristic curves, calibration curves, and decision curve analysis. And further evaluate the application value of Rad-Clinical model in clinical stages and targeted sequential therapy of HCC. RESULTS: Tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, and radiomics score (Rad-score) were found to be independent risk factors for PFS after DEB-TACE treatment for unresectable HCC, with the Rad-Clinical model being the greatest predictor of PFS in these patients (hazard ratio: 2.08; 95% confidence interval: 1.56-2.78; P < 0.001) along with high 6 months, 12 months, 18 months, and 24 months area under the curves of 0.857, 0.810, 0.843, and 0.838, respectively. In addition, compared to the radiomics and clinical nomograms, the Radiological-Clinical nomogram also significantly improved the classification accuracy for PFS outcomes, based on the net reclassification improvement (45.2%, 95% CI 0.260-0.632, p < 0.05) and integrated discrimination improvement (14.9%, 95% CI 0.064-0.281, p < 0.05). Based on this model, low-risk patients had higher PFS than high-risk patients in BCLC-B and C stages (P = 0.021). Targeted sequential therapy for patients with high and low-risk HCC in BCLC-B stage exhibited significant benefits (P = 0.018, P = 0.012), but patients with high-risk HCC in BCLC-C stage did not benefit much (P = 0.052). CONCLUSION: The Rad-Clinical model may be favorable for predicting PFS in patients with unresectable HCC treated with DEB-TACE and for identifying patients who may benefit from targeted sequential therapy.

Dynamic changes in marker components during the stir-frying of Pharbitidis Semen, and network analysis of its potential effects on nephritis.

Introduction: Pharbitidis Semen (PS) has been widely used in traditional Chinese medicine to treat several diseases such as nephritis. PS is usually stir-fried to enhance its therapeutic efficacy before use in clinical practice. However, the changes in phenolic acids during stir-frying and the mechanisms of their therapeutic effects on nephritis are still unclear. Methods: Here, we studied the processing-induced chemical changes and elucidated the mechanism of PS in the treatment of nephritis. We determined the levels of the 7 phenolic acids in raw PS (RPS) and stir-fried PS (SPS) using high-performance liquid chromatography, analyzed the dynamic compositional changes during stir-frying, and used network analysis and molecular docking to predict and verify compound targets and pathways corresponding to nephritis. Results: The dynamic changes in the 7 phenolic acids in PS during stir-frying are suggestive of a transesterification reaction. Pathway analysis revealed that the targets of nephritis were mainly enriched in the AGE-RAGE, hypoxia-inducible factor-1, interleukin-17, and tumor necrosis factor signaling pathways among others. Molecular docking results showed that the 7 phenolic acids had good binding ability with the key nephritic targets. Discussion: The potential pharmaceutical basis, targets, and mechanisms of PS in treating nephritis were explored. Our findings provide a scientific basis for the clinical use of PS in treating nephritis.

Pain Relief and Safety of Microwave Ablation Combined with Percutaneous Vertebroplasty for Vertebral Metastasis: A Pilot Study.

BACKGROUND: We investigate the pain relief and safety of microwave ablation (MWA) combined with percutaneous vertebroplasty (PVP) in the treatment of metastatic vertebral tumors. METHODS: This prospective pilot study enrolled patients with metastatic vertebral tumors treated between January 2018 and October 2019. The participants were randomized to the PVP and MWA + PVP groups. Clinical parameters, pain visual analog scale (VAS), analgesic use scores (AUS), and quality-of-life score (QLS) were compared between groups. RESULTS: Sixty-seven participants were enrolled (PVP: n = 35; MWA + PVP: n = 32). There were no differences in bone cement injection volume, extravasation, and X-ray exposure time between the two groups (p > 0.05), but treatment costs were higher for the MWA + PVP group (26,418 ± 194 vs. 15,606 ± 148 yuan; p < 0.05). There were no significant improvements in VAS from baseline to 24 hours, 72 hours, 7 days, 1 month, and 3 months in the two groups (p > 0.05); at 6 and 12 months after the operation, the improvement from baseline was significant in the two groups (p < 0.05). The VAS was lower at 6 months (2.7 ± 0.7 vs. 3.2 ± 0.7) and 12 months (3.5 ± 0.8 vs. 4.0 ± 0.7) in the MWA + PVP group (both p < 0.01 vs. PVP). The AUS and QLS were improved with PVP at 6 and 12 months (p < 0.05) and with MWA + PVP at 12 months (p < 0.05). The AUS was lower at 6 and 12 months in the MWA + PVP group (p < 0.05 vs. PVP). CONCLUSION: MWA combined with PVP might be a safe and effective palliative treatment for pain from metastatic vertebral tumors.

Initial Experience of Drug-Eluting Bead-Transcatheter Arterial Chemoembolization After Lipiodol-Based Transcatheter Arterial Chemoembolization Failure for Patients with Advanced Hepatocellular Carcinoma.

PURPOSE: To investigate the potential safety and efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in treating TACE-refractory hepatocellular carcinoma (HCC). METHODS: We retrospectively evaluated the treatment outcomes of DEB-TACE for 41 HCC nodules in 30 patients who were refractory to conventional TACE (c-TACE) according to tumor response. The antitumor response was evaluated according to mRECIST criteria, and changes in alpha-fetoprotein (AFP), albumin-bilirubin score, the incidence of adverse events, and the time to disease progression were observed. RESULTS: The objective response rate and disease control rates were 60.98% and 95.12% at 4 weeks after DEB-TACE, 63.41% and 92.68% at 8 weeks, respectively. The median time of disease progression was 4.60 ± 0.23 months. The AFP of patients decreased continuously at 2-6 weeks after operation, and the AFP at 4 weeks was significantly lower than that at 2 weeks (P = 0.038). Adverse reactions were well tolerated, and no grade 4 adverse reactions were reported. The albumin-bilirubin score did not deteriorate within 6 weeks. CONCLUSION: DEB-TACE has potential efficacy and safety after failure of c-TACE in patients with advanced liver cancer. Further studies are needed to confirm the efficacy of DEB-TACE treatment after failure of c-TACE.

Decellularized Extracellular Matrices for Tissue Engineering and Regeneration.

Decellularized extracellular matrices (dECMs) from mammalian tissues and organs are particularly interesting as scaffolds for tissue engineering and regeneration when considering their ability to retain chemical compositions and three-dimensional (3D) microstructures that are similar to native ECMs. This review discusses the advantages and disadvantages of different decellularization methods that use various agents, such as ionic and nonionic detergents and biological enzymes. The applications of dECMs as scaffolds or hydrogels for tissue engineering of specific tissues including heart valves, blood vessels, and skin, as well as their performance in vitro and in vivo, are also discussed. In addition, whole organ regeneration (i.e., the heart, kidney, liver) using dECM scaffolds has been explored, which are able to recapitulate partial functions of native organs.

Enamelin is critical for ameloblast integrity and enamel ultrastructure formation.

Mutations in the human enamelin gene cause autosomal dominant hypoplastic amelogenesis imperfecta in which the affected enamel is thin or absent. Study of enamelin knockout NLS-lacZ knockin mice revealed that mineralization along the distal membrane of ameloblast is deficient, resulting in no true enamel formation. To determine the function of enamelin during enamel formation, we characterized the developing teeth of the Enam-/- mice, generated amelogenin-driven enamelin transgenic mouse models, and then introduced enamelin transgenes into the Enam-/- mice to rescue enamel defects. Mice at specific stages of development were subjected to morphologic and structural analysis using ß-galactosidase staining, immunohistochemistry, and transmission and scanning electron microscopy. Enamelin expression was ameloblast-specific. In the absence of enamelin, ameloblasts pathology became evident at the onset of the secretory stage. Although the aggregated ameloblasts generated matrix-containing amelogenin, they were not able to create a well-defined enamel space or produce normal enamel crystals. When enamelin is present at half of the normal quantity, enamel was thinner with enamel rods not as tightly arranged as in wild type suggesting that a specific quantity of enamelin is critical for normal enamel formation. Enamelin dosage effect was further demonstrated in transgenic mouse lines over expressing enamelin. Introducing enamelin transgene at various expression levels into the Enam-/- background did not fully recover enamel formation while a medium expresser in the Enam+/- background did. Too much or too little enamelin abolishes the production of enamel crystals and prism structure. Enamelin is essential for ameloblast integrity and enamel formation.

Functions of KLK4 and MMP-20 in dental enamel formation.

Two proteases are secreted into the enamel matrix of developing teeth. The early protease is enamelysin (MMP-20). The late protease is kallikrein 4 (KLK4). Mutations in MMP20 and KLK4 both cause autosomal recessive amelogenesis imperfecta, a condition featuring soft, porous enamel containing residual protein. MMP-20 is secreted along with enamel proteins by secretory-stage ameloblasts. Enamel protein-cleavage products accumulate in the space between the crystal ribbons, helping to support them. MMP-20 steadily cleaves accumulated enamel proteins, so their concentration decreases with depth. KLK4 is secreted by transition- and maturation-stage ameloblasts. KLK4 aggressively degrades the retained organic matrix following the termination of enamel protein secretion. The principle functions of MMP-20 and KLK4 in dental enamel formation are to facilitate the orderly replacement of organic matrix with mineral, generating an enamel layer that is harder, less porous, and unstained by retained enamel proteins.

Porcine dentin sialophosphoprotein: length polymorphisms, glycosylation, phosphorylation, and stability.

Dentin sialophosphoprotein (DSPP) is critical for proper mineralization of tooth dentin, and mutations in DSPP cause inherited dentin defects. Dentin phosphoprotein (DPP) is the C-terminal cleavage product of DSPP that binds collagen and induces intrafibrillar mineralization. We isolated DPP from individual pigs and determined that its N-terminal and C-terminal domains are glycosylated and that DPP averages 155 phosphates per molecule. Porcine DPP is unstable at low pH and high temperatures, and complexing with collagen improves its stability. Surprisingly, we observed DPP size variations on SDS-PAGE for DPP isolated from individual pigs. These variations are not caused by differences in proteolytic processing or degrees of phosphorylation or glycosylation, but rather to allelic variations in Dspp. Characterization of the DPP coding region identified 4 allelic variants. Among the 4 alleles, 27 sequence variations were identified, including 16 length polymorphisms ranging from 3 to 63 nucleotides. None of the length variations shifted the reading frame, and all localized to the highly redundant region of the DPP code. The 4 alleles encode DPP domains having 551, 575, 589, or 594 amino acids and completely explain the DPP size variations. DPP length variations are polymorphic and are not associated with dentin defects.

[Expression of calponin and P63 in human submandibular glands].

OBJECTIVE: To observe the expression of new myoepithelial cell markers calponin and P63 in human submandibular glands. METHODS: Calponin and P63 antigen in routinely processed human submandibular gland tissues were immunohistochemically demonstrated by monoclonal antibodies to calponin and P63. RESULTS: Calponin expressed around all acinus and intercalated ducts as linear or punctuate pattern. Positive staining was also noted in peripheral area of some thin striated ducts that connect to intercalated ducts. Subulate or trigonal calponin expression was sometimes seen between the duct dells of striated ducts. P63 expressed mainly in the nucleus of the basal cells of excretory duct. CONCLUSION: Calponin is an ideal gland. P63 labels mainly the basal cells of excretory duct. marker for myoepithelial cells of human submandibular