Liver transplantation for intrahepatic cholangiocarcinoma: a propensity score-matched analysis.

Liver resection (LR) is the only recommended effective curative treatment for patients with intrahepatic cholangiocarcinoma (ICC), but the prognosis of patients with ICC is still poor even after curative resection. Recently, many researchers focused on the therapeutic value of LT for patients with ICC. This study aimed to identify the role of liver transplantation in patients with ICC by internally comparing with LR in ICC and externally comparing with LT in HCC. We obtained patient data from SEER database. Propensity score methods were applied to control confounders. Survival outcome was estimated using Kaplan-Meier survival curves and compared using the log-rank test. A total of 2538 patients with ICC after surgery and 5048 patients with HCC after LT between 2000 and 2019 were included in this study. The prognosis of patients with ICC after LT were better than patients with ICC after LR in both unmatched (HR 0.65, P = 0.002) and matched cohorts (HR 0.62, P = 0.009). The 5-year OS rate after LT could be improved to 61.7% in patients with local advanced ICC after neoadjuvant chemotherapy. In conclusion, our study demonstrated that the prognosis of patients with ICC after LT was better than patients with ICC after LR, but was still worse than patients with HCC after LT. LT with neoadjuvant chemotherapy should be considered as a treatment option for patients with locally advanced ICC, but more prospective multicenter clinical trials are needed to further confirm these results.

Adhesive anastomosis for organ transplantation.

The recent development of tough tissue adhesives has stimulated intense interests among material scientists and medical doctors. However, these adhesives have seldom been tested in clinically demanding surgeries. Here we demonstrate adhesive anastomosis in organ transplantation. Anastomosis is commonly conducted by dense sutures and takes a long time, during which all the vessels are occluded. Prolonged occlusion may damage organs and even cause death. We formulate a tough, biocompatible, bioabsorbable adhesive that can sustain tissue tension and pressurized flow. We expose the endothelial surface of vessels onto a gasket, press two endothelial surfaces to the adhesive using a pair of magnetic rings, and reopen the bloodstream immediately. The time for adhesive anastomosis is shortened compared to the time for sutured anastomosis. We have achieved adhesive anastomosis of a great vein in transplanting the liver of a pig. After the surgery, the adhesive is absorbed, the vein heals, and the pig lives for over one month.

Prognostic nomogram for cancer-specific survival in patients with intrahepatic cholangiocarcinoma after hepatectomy: A population study of 919 patients.

Background and Aims: Intrahepatic cholangiocarcinoma has an increasing global incidence and mortality rate. Hepatectomy is still the most effective curative treatment for patients with ICC, but the prognosis of patients with ICC is still poor even after curative resection. This study aimed to incorporate important factors obtained from SEER database to construct and validate a nomogram for predicting the cancer-specific survival of patients with ICC after hepatectomy. Methods: We obtained patient data from SEER database. The nomogram was constructed base on six prognostic factors for predicting CSS rates in ICC patients. The nomogram was validated by C-index, ROC curve and calibration curves. Results: A total of 919 patients with ICC after hepatectomy between 2000 and 2018 were included in this study. A nomogram based on six independent prognostic factors (Black race, AJCC T, AJCC N, AJCC M, chemotherapy and PLNR ≥ 0.15) was developed for the prediction of CSS at 3 and 5 years. The C-index of the nomogram and AJCC stage system were 0.709 and 0.657 in the training cohort respectively. The 3- and 5-year AUCs of nomogram were 0.744 and 0.75 in the training cohort. The calibration plots indicated that there was good agreement between the actual observations and predictions. Conclusions: In conclusion, we constructed and validated a nomogram for predicting the 3- and 5-year CSS in ICC patients after hepatectomy. We have confirmed the precise calibration and acceptable discrimination power of our nomogram. The predictive power of this nomogram may be improved by considering other potential important factors and also by external validation.

Natural Killer-Like B Cells Secreting Interleukin-18 Induces a Proinflammatory Response in Periodontitis.

Natural killer-like B (NKB) cells, which are newly identified immune subsets, reveal a critical immunoregulatory property in the eradication of microbial infection via the secretion of interleukin (IL)-18. For the first time, this study investigated the role of NKB cells in secreting IL-18 in the pathogenesis of periodontitis. In this study, NKB cells' percentage and IL-18 concentration in peripheral blood and periodontium in periodontitis patients was measured using flow cytometry and ELISA. The role of IL-18 in regulating periodontal inflammation was examined in a Porphyromonas gingivalis (P. gingivalis)-induced periodontitis murine model. Peripheral and periodontal-infiltrating CD3-CD19+NKp46+ NKB cells, which were the main source of IL-18, were elevated and correlated with attachment loss in periodontitis patients. In vitro IL-18 stimulation promoted proinflammatory cytokine production in periodontal ligament cells. P. gingivalis infection induced elevation of IL-18 receptor in periodontium in a periodontitis murine model. IL-18 neutralization not only suppressed P. gingivalis-induced alveolar bone resorption, but also inhibited recruitment of antigen-non-specific inflammatory cells into the periodontium, probably via dampening expressions of cytokines, chemokines, and matrix metalloproteinases. NKB cells secreting IL-18 appeared to be an important mediator in the inflammatory response following intraoral P. gingivalis infection. These findings might be relevant to the development of immunotherapies for periodontitis.

Oridonin inhibits epithelial-mesenchymal transition of human nasopharyngeal carcinoma cells by negatively regulating AKT/STAT3 signaling pathway.

Oridonin, derived from Rabdosia rubescens, has exhibited anticancer activity in a variety of cancers. However, few studies have explored the effect of oridonin (ORI) on migration, invasion and epithelial-mesenchymal transition (EMT) in nasopharyngeal carcinoma. In our study, the results demonstrated that oridonin significantly inhibited migration and invasion of human nasopharyngeal carcinoma CNE-2Z and HNE-1 cell lines, as depicted by wound healing and Transwell assays. In addition, oridonin increased the expression of E-Cadherin while decreased the expressions of vimentin and twist1 at the mRNA and protein levels in a dose-dependent manner. Interestingly, oridonin also decreased cell mobility in nasopharyngeal carcinoma. The subsequent results of western blotting uncovered that the phosphorylation levels of AKT and signal transducer and activator of transcription 3 (STAT3) were decreased upon oridonin treatment. Furthermore, co-treatment with the AKT activator SC-79 attenuated the anti-metastatic effect of oridonin on nasopharyngeal carcinoma and partially abolished the high expression of E-cadherin and the low expression of twist1 mediated by oridonin. In conclusion, the results revealed that oridonin could repress metastatic phenotype and reverse epithelial-mesenchymal transition (EMT) in nasopharyngeal carcinoma by negatively regulating AKT/STAT3 signaling pathway, suggesting that AKT/STAT3 signaling may be the potential therapeutic target of oridonin against nasopharyngeal carcinoma.

Construction and validation of a nomogram for predicting cancer-specific survival in hepatocellular carcinoma patients.

The prognosis of patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is a research hotspot. This study aimed to incorporate important factors obtained from SEER database to construct and validate a nomogram for predicting the cancer-specific survival (CSS) of patients with HCC and ICC. We obtained patient data from SEER database. The nomogram was constructed base on six prognostic factors for predicting CSS rates in HCC patients. The nomogram was validated by concordance index (C-index), the receiver operating characteristic (ROC) curve and calibration curves. A total of 3227 patients diagnosed with HCC (3038) and ICC (189) between 2010 and 2015 were included in this study. The C-index of the nomogram for HCC patients was 0.790 in the training cohort and 0.806 in the validation cohort. The 3- and 5-year AUCs were 0.811 and 0.793 in the training cohort. The calibration plots indicated that there was good agreement between the actual observations and predictions. In conclusion, we constructed and validated a nomogram for predicting the 3- and 5-year CSS in HCC patients. We have confirmed the precise calibration and excellent discrimination power of our nomogram.

Role of linker histone H1c during the reprogramming of Chinese swamp buffalo (Bubalus Bubalis) embryos produced by somatic cell nuclear transfer.

During reprogramming, there is exchange of histone H1c and the oocyte-specific linker histone, and H1c may play a critically important role in the reprogramming process of somatic cell nuclear transfer (SCNT). The aim of the present study was to investigate the role of the H1c gene in SCNT reprogramming in Chinese swamp buffalo (Bubalus bubalis) using RNA interference (RNAi). Chinese swamp buffalo H1c gene sequences were obtained and H1c-RNAi vectors were designed, synthesised and then transfected into a buffalo fetal skin fibroblast cell line. Expression of H1c was determined by real-time polymerase chain reaction to examine the efficiency of vector interference. These cells were then used as a nuclear donor for SCNT so as to observe the further development of SCNT embryos. Inhibition of H1c gene expression in donor cells significantly improved the developmental speed of embryos from the 1-cell to 8-cell stage. Furthermore, compared with the control group, inhibition of H1c gene expression significantly reduced the blastocyst formation rate. It is concluded that linker histone H1c is very important in SCNT reprogramming in Chinese swamp buffalo. Correct expression of the H1c gene plays a significant role in preimplantation embryonic development in B. bubalis.

[Effect of TSA and VPA treatment on long-tailed macaque (Macaca fascicularis)-pig interspecies somatic cell nuclear transfer].

Long-tailed macaque-pig interspecies somatic cell nuclear transfer (iSCNT) is beneficial to yield embryonic stem cells from iSCNT embryos with similar genetic background as human, which can be used as materials for medical and basic research. The primary objective of this study was to investigate the effects of concentrations and treatment duration of two histone deacetylase inhibitors-Trichostatin A (TSA) and Valproic acid (VPA) and two different embryo culture media (PZM-3 and HECM-10) on the in vitro development of iSCNT embryos. The results suggested that when PZM-3 was used as the embryo culture medium, the blastocyst rate of 10 nmol/L TSA treatment for 48 h was significantly higher than the control group (22.78% vs 9.86%, P< 0.05). However, neither in PZM-3 nor in HECM-10, 2-10 mmol/L VPA treatment did not increase the in vitro developmental potential of iSCNT embryos. It was concluded that TSA treatment could enhance the in vitro developmental potential of long-tailed macaque-pig iSCNT embryos.