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Background The aim of this study was to establish and validate an easy-to-use nomogram to predict portal vein thrombosis (PVT) in patients with cirrhosis after splenectomy and to test its predictive ability. Material/Methods This retrospective study included 315 patients with cirrhosis who underwent splenectomy at 2 high-volume medical centers. The least absolute shrinkage and selection operator (LASSO) regression method was used to select the predictors in the training cohort, and multivariable logistic regression analysis was performed to establish the predictive nomogram model. We determined the prediction value of the nomogram by the area under the receiver operating characteristic curve (AUROC), the calibration curve, and decision curve analysis. Finally, the applicability of the nomogram was internally and independently validated. Results The predictors of PVT included portal vein diameter, splenic vein diameter, body mass index, and platelet count. Based on the clinical and radiomic models, the nomogram had good predictive efficiency for predicting PVT in patients with cirrhosis after splenectomy, with an AUROC of 0.887 (0.856 in internal validation and 0.796 in independent validation). The decision curve analysis revealed that the nomogram had good clinical application value. Conclusions We successfully developed an easy-to-use nomogram to predict the probability of PVT in patients with cirrhosis after splenectomy. The nomogram can help clinicians make timely, individualized clinical decisions for PVT in patients with cirrhosis after splenectomy.
Tunneling nanotubes (TNTs) are F-actin-based membrane tubes, and can form between cultured cells and within vital tissues. TNTs mediate intercellular communications that range from electrical signaling to the transfer of organelles. Following peripheral nerve injury, the orchestrated intercellular communications among neural and non-neural cells are required for effective nerve regeneration. It remains unknown whether TNTs exist between neural cells in the peripheral nerve system and how TNTs affect neural regeneration. To address these interesting questions, we investigated the transfer of neurotropic factors, membrane protein, cytoplasmic protein, mitochondria and RNA in functional TNTs formed between cultured Schwann cells (SCs). TNT-like structures were increased not only in cultured SCs after exposure to serum depletion but also in longitudinal sections of proximal sciatic nerve stump harvested after rat peripheral nerve transection. Meanwhile, downregulation of Rab8a or Rab11a in cultured SCs inhibited the formation of functional TNTs and vesicle transfer and led to decrease in cell migration, increase in SCs apoptosis. Likewise, knockdown of Rab8a or Rab11a in primary SCs also suppressed axonal outgrowth from co-cultured dorsal root ganglion (DRG) neurons. Overall, our results suggested that the gene of Rab8a or Rab11a might be involved in the formation of TNTs structures in the peripheral nerve system, while TNTs structures were likely to affect peripheral nerve regeneration through the regulation of neural cell communications.
A combination of gene therapy and chemotherapy has recently received interest as a targeted therapy for glioma. A mesoporous silica nanoparticle (MSN)-based vehicle coated with IL13Rα2-targeted peptide (IP) using polyethylene glycol (PEG), MSN-PEG-IP (MPI), was constructed and confirmed as a potential glioma-targeted drug delivery system in vitro. In this work, tissue microarray (TMA) results revealed that IL13Rα2 was over-expressed in human glioma tissues and that high expression of IL13Rα2 in patients was associated with poor survival. Doxorubicin (DOX)-loaded MPI (MPI/D) crossed the blood-brain barrier, specifically targeting glioma cells and significantly enhancing the cellular uptake of DOX in glioma cells compared with MSN/DOX (M/D) and MSN-PEG/DOX (MP/D), whereas the normal brain was not affected. Magnetic Resonance Imaging (MRI) examinations showed that the tumour size of glioma-bearing rats in the MPI/D-treated group was much smaller than those in the M/D and MP/D treated groups. Immunofluorescence results demonstrated that MPI/D treatment induced more apoptosis and much less proliferation than the other two treatments. However, the therapeutic effect was weak when IL13Rα2 was knocked down. Furthermore, U87 cells treated with IL-13 and MPI together could increase both STAT6 and P63 expression, which attenuated glioma cell proliferation, invasion and migration compared with cells treated with IL-13 alone. The results of the subcutaneous tumour model also revealed that IL13Rα2 knockdown could hinder cell proliferation and induce more apoptosis. The promising results suggested that MPI can not only deliver DOX to glioma in a targeted manner but also occupy IL13Rα2, which can promote IL-13 binding to IL13Rα1 and activation of the JAK-STAT pathway to induce an anti-glioma effect.
tRNA-derived fragments (tRFs) are a novel class of small non-coding RNAs (sncRNAs) whose biological roles are not well defined. Here, using multiple approaches, we investigated its role in human triple-negative breast cancer (TNBC). Our genome-wide transcriptome analysis of sncRNAs revealed that tRF Lys-CTT-010 was significantly increased in human TNBC. It promoted TNBC proliferation and migration. It also closely associated with starch and sucrose metabolism pathways (KEGG analysis) and positively regulated the expression of glucose-6-phosphatase catalytic subunit (G6PC), one of the related genes in the pathway. G6PC, a complex of glucose-6-phosphatase in gluconeogenesis and glycogenolysis, is upregulated in human TNBC samples. Further studies demonstrated that overexpression of G6PC in tRF Lys-CTT-010 inhibitor transfected TNBC cell lines can reverse malignant biological behavior and knockdown of G6PC in TNBC cell lines inhibited tumor progression and reversed the oncogenic function of tRF Lys-CTT-010. In addition, tRF Lys-CTT-010 interacted with G6PC to regulate cellular lactate production and glycogen consumption, resulting in cell survival and proliferation. Thus, fine-tuneing glucose metabolism and the tRF Lys-CTT-010 /G6PC axis may provide a therapeutic target for TNBC treatment.
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