Special ArticleBackground. Nearly 40 y have passed since the 1983 National Institutes of Health Consensus-Development-Conference, which has turned liver transplantation (LT) from a clinical experiment into a routine therapeutic modality. Since‚ clinical LT has changed substantially. We aimed to comprehensively analyze the publication trends in the most-cited top-notch literature in LT science over a 4-decade period. Methods. A total of 106 523 items were identified between January 1981 and May 2021 from the Web of Science Core Collection. The top 100 articles published were selected using 2 distinct citation-based strategies to minimize bias. Various bibliometric tools were used for data synthesis and visualization. Results. The citation count for the final dataset of the top 100 articles ranged from 251 to 4721. Most articles were published by US authors (n = 61). The most prolific institution was the University of Pittsburgh (n = 15). The highest number of articles was published in Annals of Surgery, Hepatology, and Transplantation; however, Hepatology publications resulted in the highest cumulative citation of 9668. Only 10% of the articles were classified as evidence level 1. Over 90% of first/last authors were male. Our data depict the evolution of research focus over 40 y. In part, a disproportional flow of citations was observed toward already well-cited articles. This might also project a slowed canonical progress, which was described in other fields of science.Conclusions. This study highlights key trends based on a large dataset of the most-cited articles over a 4-decade period. The present analysis not only provides an important cross-sectional and forward-looking guidance to clinicians, funding bodies, and researchers but also draws attention to important socio-academic or demographic aspects in LT.

Background: Peptidylarginine deiminase 1 (PADI1) has been reported to promote tumorigenesis in breast cancer. However, the functional role of PADI1 in pancreatic ductal adenocarcinoma (PAAD) has remained elusive until now. Methods:The expression pattern of PADI1 in PAAD tissues and normal tissues was analyzed using The Cancer Genome Atlas (TCGA) dataset. A Kaplan-Meier curve analysis was performed to evaluate the prognostic value of PADI1 in PAAD patients. PADI1 was knocked down in CFPAN-1 and HPAC cells, and overexpressed in PANC-1 and Bxpc-3 cells by RNA interference. A wound-healing assay was performed to analyze relative cell migration distance. Cell migration and invasion were assessed by a Transwell assay.Related protein expression levels were measured by western blot and immunofluorescence.Results: The bioinformatics analysis showed that PADI1 was overexpressed in PAAD tissues and associated with a poor survival prognosis. The knockdown of PADI1 suppressed cell migration and invasion, and activated the ERK1/2-p38 signaling pathway in CFPAN-1 and HPAC cells. The overexpression of PADI1 produced the opposite results in PANC-1 and Bxpc-3 cells. Additionally, treatment with an MEK1/2 inhibitor significantly attenuated the effects of PADI1 knockdown on cell migration, invasion, the epithelialmesenchymal transition (EMT) process, and p-ERK1/2 and p38 expression in CFPAN-1 and HPAC cells.Conclusions: Our data suggested that PADI1 may function as an oncogene in regulating metastasis in vitro in PAAD.

Background. Acute pancreatitis (AP) is a common surgical acute abdomen. Different kinds of pancreatitis may have different pathophysiological characteristics each other. The objective of this research was to investigate the early clinical features and complications of different types of acute pancreatitis. Methods. 787 AP patients admitted in the Huadu District People’s Hospital of Guangzhou during January 2009 and December 2019 were analyzed retrospectively. Among 787 AP patients, 520 (66.1%) were biliary AP (group I), 69 (8.7%) were alcoholic AP (group II), and 198 (25.2%) were hypertriglyceridemic AP (group III). According to the local and systemic complications and mortality in the early stage, we compared and analyzed the clinical characteristics and prognosis of different types of pancreatitis. Results. Mild acute pancreatitis accounted for the highest proportion (79.4%) in group I, while moderately severe acute pancreatitis in group II (36.2%) and severe acute pancreatitis in group III (62.6%). In terms of severity score of the pancreatitis, the average scores of BISAP, Ranson, APACHE-II, and MCTSI of the patients in group III were the highest ( p < 0.01 ). The incidence of acute peripancreatic fluid collection and infectious pancreatic necrosis was the highest in group III. The incidences of acute necrotic collection, pancreatic pseudocyst, and walled-off necrosis in group III were significantly higher than those in the other two groups ( p < 0.01 ). The incidences of systemic inflammatory response syndrome, sepsis, multiple organ failure, intra-abdominal hypertension, and mortality were highest in group III. Conclusions. There is an upward trend of the incidence rate of hypertriglyceridemic AP in recent years; it has been gradually developed into the second type of acute pancreatitis which is second only to the acute biliary pancreatitis. It is worthy to pay more and more attentions to it due to the feature of its younger onset, high incidence of complications, and high mortality.

Perineural invasion (PNI) is considered to be a main reason for the poor prognosis of pancreatic cancer. In the present study, we analyzed the roles of substance P (SP)/neurokinin-1 receptor (NK-1R) and lncRNA LOC389641 in pancreatic cancer PNI. Pancreatic cancer cell lines BxPC-3 and MIAPaCa-2 were cocultured with SH-SY5Y cells and then stimulated with SP to simulate the in vivo influence of ganglia on pancreatic cancer. The BxPC-3 and MIAPaCa-2 cells were transfected with a neurokinin-1 receptor (NK-1R) overexpression vector, NK-1R silencing vector, LOC389641 overexpression vector, or LOC389641 silencing vector, respectively. The proliferative abilities of BxPC-3 and MIAPaCa-2 cells were assessed using the cell counting kit-8 and 5-ethynyl-2 ′ -deoxyuridine (EdU) assays. Wound-healing and Transwell assays were performed to determine the migration and invasion abilities of the cells. When SP was added to the coculture system, it positively regulated cancer cell proliferation, migration, and PNI and significantly activated the NK-1R/Akt/NF-κB signaling pathway. Incubation with 100 nmol/L SP for 24 h was selected as the optimal condition for treatment. The activated NK-1R positively regulated the proliferation, migration, and invasion of pancreatic cancer cells. However, the levels of lncRNA LOC389641 and tumor necrosis factor receptor SF10A (TNFRSF10A) mRNA in BxPC-3 and MIAPaCa-2 cells were not affected by SP treatment. Overexpression or silencing of LOC389641 changed the effect of SP stimulation on pancreatic cancer PNI. When taken together, these results revealed that SP/NK-1R and LOC389641 promoted the progression of pancreatic cancer PNI. Moreover, we found that pancreatic cancer PNI promoted by the SP/NK-1R axis could be blocked by the TNFRSF10A/NF-κB pathway mediated by LOC389641.

Objective: Pancreatic adenocarcinoma (PAAD) is a highly malignant gastrointestinal tumor with almost similar morbidity and mortality. In this study, based on bioinformatics, we investigated the role of gene methylation in PAAD, evaluated relevant factors affecting patient prognosis, screened potential anti-cancer small molecule drugs, and constructed a prediction model to assess the prognosis of PAAD.Methods: Clinical and genomic data of PAAD were collected from the Tumor Genome Atlas Project (TCGA) database and gene expression profiles were obtained from the GTEX database. Analysis of differentially methylated genes (DMGs) and significantly differentially expressed genes (DEGs) was performed on tumorous samples with KRAS wild-type and normal samples using the “limma” package and combined analysis. We selected factors significantly associated with survival from the significantly differentially methylated and expressed genes (DMEGs), and their fitting into a relatively streamlined prognostic model was validated separately from the internal training and test sets and the external ICGC database to show the robustness of the model.Results: In the TCGA database, 2,630 DMGs were identified, with the largest gap between DMGs in the gene body and TSS200 region. 318 DEGs were screened, and the enrichment analysis of DMGs and DEGs was taken to intersect DMEGs, showing that the DMEGs were mainly related to Olfactory transduction, natural killer cell mediated cytotoxicity pathway, and Cytokine -cytokine receptor interaction. DMEGs were able to distinguish well between PAAD and paraneoplastic tissues. Through techniques such as drug database and molecular docking, we screened a total of 10 potential oncogenic small molecule compounds, among which felbamate was the most likely target drug for PAAD. We constructed a risk model through combining three DMEGs (S100P, LY6D, and WFDC13) with clinical factors significantly associated with prognosis, and confirmed the model robustness using external and internal validation.Conclusion: The classification model based on DMEGs was able to accurately separate normal samples from tumor samples and find potential anti-PAAD drugs by performing gene-drug interactions on DrugBank.