DrugRepoBank: a comprehensive database and discovery platform for accelerating drug repositioning.

In recent years, drug repositioning has emerged as a promising alternative to the time-consuming, expensive and risky process of developing new drugs for diseases. However, the current database for drug repositioning faces several issues, including insufficient data volume, restricted data types, algorithm inaccuracies resulting from the neglect of multidimensional or heterogeneous data, a lack of systematic organization of literature data associated with drug repositioning, limited analytical capabilities and user-unfriendly webpage interfaces. Hence, we have established the first all-encompassing database called DrugRepoBank, consisting of two main modules: the 'Literature' module and the 'Prediction' module. The 'Literature' module serves as the largest repository of literature-supported drug repositioning data with experimental evidence, encompassing 169 repositioned drugs from 134 articles from 1 January 2000 to 1 July 2023. The 'Prediction' module employs 18 efficient algorithms, including similarity-based, artificial-intelligence-based, signature-based and network-based methods to predict repositioned drug candidates. The DrugRepoBank features an interactive and user-friendly web interface and offers comprehensive functionalities such as bioinformatics analysis of disease signatures. When users provide information about a drug, target or disease of interest, DrugRepoBank offers new indications and targets for the drug, proposes new drugs that bind to the target or suggests potential drugs for the queried disease. Additionally, it provides basic information about drugs, targets or diseases, along with supporting literature. We utilize three case studies to demonstrate the feasibility and effectiveness of predictively repositioned drugs within DrugRepoBank. The establishment of the DrugRepoBank database will significantly accelerate the pace of drug repositioning. Database URL:  https://awi.cuhk.edu.cn/DrugRepoBank.

YTHDC1 promotes the malignant progression of gastric cancer by promoting ROD1 translocation to the nucleus.

RNA-binding proteins (RBPs) make vital impacts on tumor progression and are important potential targets for tumor treatment. Previous studies have shown that RBP regulator of differentiation 1 (ROD1), enriched in the nucleus, is abnormally expressed and functions as a splicing factor in tumors; however, the mechanism underlying its involvement in gastric cancer (GC) is unknown. In this study, ROD1 is found to stimulate GC cell proliferation and metastasis and is related to poor patient prognosis. In vitro experiments showed that ROD1 influences GC proliferation and metastasis through modulating the imbalance of the level of the oncogenic gene OIP5 and the tumor suppressor gene GPD1L. Further studies showed that the N6-methyladenosine (m6A) "reader" protein YTHDC1 can interact with ROD1 and regulate the balance of the expression of the downstream molecules OIP5/GPD1L by promoting the nuclear enrichment of ROD1. Therefore, YTHDC1 stimulates GC development and progression through modulating nuclear enrichment of the splicing factor ROD1.

Comparison of thoracoabdominal versus abdominal-transhiatal surgical approaches in Siewert type II adenocarcinoma at the esophagogastric junction: Protocol for a prospective multicenter randomized controlled trial.

Background: Siewert type II adenocarcinoma of the esophagogastric junction (Siewert II AEG) can be resected by the right thoracoabdominal surgical approach (RTA) or abdominal-transhiatal surgical approach (TH) under minimally invasive conditions. Although both surgical methods achieve complete tumor resection, there is a debate as to whether the former method is superior to or at least noninferior to the latter in terms of surgical safety. Currently, a small number of retrospective studies have compared the two surgical approaches, with inconclusive results. As such, a prospective multicenter randomized controlled trial is necessary to validate the value of RTA (Ivor-Lewis) compared to TH. Methods: The planned study is a prospective, multicenter, randomized clinical trial. Patients (n=212) with Siewert II AEG that could be resected by either of the above two surgical approaches will be included in this trial and randomized to the RTA group (n=106) or the TH group (n=106). The primary outcome will be 3-year disease-free survival (DFS). The secondary outcomes will include 5-year overall survival (OS), incidence of postoperative complications, postoperative mortality, local recurrence rate, number and location of removed lymph nodes, quality of life (QOL), surgical Apgar score, and duration of the operation. Follow-ups are scheduled every three months for the first 3 years after the surgery and every six months for the next 2 years. Discussion: Among Siewert II AEG patients with resectable tumors, this is the first prospective, randomized clinical trial comparing the surgical safety of minimally invasive RTA and TH. RTA is hypothesized to provide better digestive tract reconstruction and dissection of mediastinal lymph nodes while maintaining a high quality of life and good postoperative outcome. Moreover, this trial will provide a high level of evidence for the choice of surgical procedures for Siewert II AEG. Clinical trial registration: Chinese Ethics Committee of Registering Clinical Trials, identifier (ChiECRCT20210635); Clinical Trial.gov, identifier (NCT05356520).

Different 18F-FDG imaging: A rare case of liver multiple carcinomas.

A 49-year-old man was referred to the hospital with the complaints of haematochezia and weight loss. Colonoscopy and pathological needle biopsy suggested moderately to highly differentiated adenocarcinoma. The patient underwent abdominal CT examination, which demonstrated two augmented and irregular masses in the liver. However, the glucose metabolism of 18F-FDG in these two lesions was completely different. Considering the different glucose metabolism, a needle biopsy of the liver mass was performed, and the diagnosis was rectal cancer with liver metastasis and primary hepatocellular carcinoma.

Prognostic model based on m6A-associated lncRNAs in esophageal cancer.

Background: This research aimed to build an m6A-associated lncRNA prognostic model of esophageal cancer that can be used to predict outcome in esophageal cancer patients. Methods: RNA sequencing transcriptome data and clinical information about patients with esophageal cancer were obtained according to TCGA. Twenty-four m6A-associated genes were selected based on previous studies. m6A-associated lncRNAs were determined through Pearson correlation analysis. Three m6A-associated lncRNA prognostic signatures were built through analysis of the training set using univariate, LASSO, and multivariate Cox regression. To validate the stabilization of the risk signature, Kaplan-Meier and ROC curve analyses were performed on the testing and complete sets. The prognoses of EC patients were predicted quantitatively by building a nomogram. GSEA was conducted to analyze the underlying signaling pathways and biological processes. To identify the underlying mechanisms through which the lncRNAs act, we constructed a PPI network and a ceRNA network and conducted GO and KEGG pathway analyses. EC samples were evaluated using the ESTIMATE algorithm to compute stromal, immune, and estimate scores. The ssGSEA algorithm was used to quantitatively infer immune cell infiltration and immune functions. The TIDE algorithm was performed to simulate immune evasion and predict the response to immunotherapy. Results: We identified and validated an m6A-associated lncRNA risk model in EC that could correctly and reliably predict the OS of EC patients. The ceRNA network, PPI network, and GO and KEGG pathway analyses confirmed and the underlying mechanisms and functions provided enlightenment regarding therapeutic strategies for EC. Immunotherapy responses were better in the low-risk subgroup, and PD-1 and CTLA4 checkpoint immunotherapy benefited the patients in the low-risk subgroup. Conclusions: We constructed a new m6A-related lncRNA prognostic risk model of EC, based on three m6A-related lncRNAs: LINC01612, AC025166.1 and AC016876.2, that can predict the prognoses of EC patients.

Study protocol for feasibility and safety of adopting early oral feeding in post total laparoscopic total gastrectomy (overlap esophagojejunostomy): A multicentre randomized controlled trial.

Background: Total laparoscopic total gastrectomy (TLTG) for gastric cancer, especially with overlap esophagojejunostomy, has been verified that it has advantages of minimally invasion, less intraoperative bleeding, and faster recovery. Meanwhile, early oral feeding (EOF) after the operation has been demonstrated to significantly promote early rehabilitation in patients, particularly with distal gastrectomy. However, due to the limited application of TLTG, there is few related research proving whether it is credible or safe to adopt EOF after TLTG (overlap esophagojejunostomy). So, it is urgent to start a prospective, multicenter, randomized clinical trials to supply high level evidence. Methods/design: This study is a prospective, multicenter, randomized controlled trial with 200 patients (100 in each group). These eligible participants are randomly allocated into two different groups, including EOF group and delay oral feeding (DOF) group after TLTG (overlap esophagojejunostomy). Anastomotic leakage will be carefully observed and recorded as the primary endpoints; the period of the first defecation and exhaust, postoperative length of stay and hospitalization expenses will be recorded as secondary endpoints to ascertain the feasibility and safety of adopting EOF after TLTG (overlap esophagojejunostomy). Discussion: Recently, the adoption of TLTG was limited due to its difficult anastomotic procedure, especially in vivo esophagojejunostomy. With the innovation and improvement of operating techniques, overlap esophagojejunostomy with linear staplers simplified the anastomotic steps and reduced operational difficulties after TLTG. Meanwhile, EOF had received increasing attention from surgical clinicians as a nutrition part of enhanced recovery after surgery (ERAS), which had shown better results in patients after distal gastrectomy. Considering the above factors, we implemented EOF protocol to evaluate the feasibility and safety of adopting EOF after TLTG (overlap esophagojejunostomy), which provided additional evidence for the development of clinical nutrition guidelines. Clinical trial registration: [www.chictr.org.cn], identifier [ChiECRCT20200440 and ChiCTR2000040692].

Comparison of the Efficacy of D2 Gastrectomy Plus Liver Radiofrequency Combined With Chemotherapy Versus Chemotherapy Alone in the Treatment of Advanced Gastric Cancer With Unresectable Synchronous Liver Metastases: A Multicenter Randomized Controlled Trial Protocol.

Background: Whether patients with advanced gastric cancer with unresectable synchronous liver metastases require surgical treatment remains a controversial topic among surgeons. Recently, an open-label multicenter, international RCT study show that compared with chemotherapy alone, gastric resection combined with chemotherapy had no survival advantage for advanced gastric cancer with unresectable synchronous liver metastases. A limitation of this study was that gastrectomy for gastric cancers was restricted to D1 lymphadenectomy and no metastatic lesions were removed. Whether D2 gastrectomy plus liver radiofrequency plus postoperative chemotherapy could provide benefits to these patients is worthy of further confirmation by high-level evidence-based medicine. Methods/Design: This study will investigate the efficacy of D2 gastrectomy plus liver radiofrequency plus postoperative chemotherapy compared to chemotherapy alone in a prospective, multicenter, randomized controlled trial that will enroll 200 patients who have advanced gastric cancer with unresectable synchronous liver metastases. The patients will be randomly divided into two groups: the test group (D2 gastrectomy plus liver radiofrequency plus postoperative chemotherapy, n=100) and the control group (chemotherapy alone, n=100). The patients' general information, past medical history, laboratory tests, imaging results, surgery details, and chemotherapy details will be recorded and analysed. The overall survival (OS) will be recorded as primary endpoints. Progression-free survival (PFS) and the total incidence of complications will be recorded as secondary endpoints. Discussion: This study is to establish a multicentre randomized controlled trial to compare the efficacy of D2 gastrectomy plus liver radiofrequency combined with postoperative chemotherapy versus chemotherapy alone. Trial Registration: Chinese Clinical Trial Registry, Approved No. of ethics committee:ChiECRCT20200331. Registered on 15 November 2020. Registration number:ChiCTR2000039964. The study has received full ethical and institutional approval. Advantages and Limitations of this Study: This is the first clinical trial that will provide evidence on the efficacy of D2 gastrectomy plus liver radiofrequency combined with chemotherapy versus chemotherapy alone for the treatment of advanced gastric cancer with unresectable synchronous liver metastases. A prospective RCT with 200 patients who have advanced gastric cancer with unresectable synchronous liver metastases. Clinical Trial Registration: [https://www.chictr.org.cn/], identifier ChiCTR2000039964.