Circulating tumor cell-derived exosome-transmitted long non-coding RNA TTN-AS1 can promote the proliferation and migration of cholangiocarcinoma cells.

BACKGROUND: Exosomes assume a pivotal role as essential mediators of intercellular communication within tumor microenvironments. Within this context, long noncoding RNAs (LncRNAs) have been observed to be preferentially sorted into exosomes, thus exerting regulatory control over the initiation and progression of cancer through diverse mechanisms. RESULTS: Exosomes were successfully isolated from cholangiocarcinoma (CCA) CTCs organoid and healthy human serum. Notably, the LncRNA titin-antisense RNA1 (TTN-AS1) exhibited a conspicuous up-regulation within CCA CTCs organoid derived exosomes. Furthermore, a significant elevation of TTN-AS1 expression was observed in tumor tissues, as well as in blood and serum exosomes from patients afflicted with CCA. Importantly, this hightened TTN-AS1 expression in serum exosomes of CCA patients manifested a strong correlation with both lymph node metastasis and TNM staging. Remarkably, both CCA CTCs organoid-derived exosomes and CCA cells-derived exosomes featuring pronounced TTN-AS1 expression demonstrated the capability to the proliferation and migratory potential of CCA cells. Validation of these outcomes was conducted in vivo experiments. CONCLUSIONS: In conclusion, our study elucidating that CCA CTCs-derived exosomes possess the capacity to bolster the metastasis tendencies of CCA cells by transporting TTN-AS1. These observations underscore the potential of TTN-AS1 within CTCs-derived exosomes to serve as a promising biomarker for the diagnosis and therapeutic management of CCA.

Puerarin protects the fatty liver from ischemia-reperfusion injury by regulating the PI3K/AKT signaling pathway

Abstract The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway.

Puerarin protects the fatty liver from ischemia-reperfusion injury by regulating the PI3K/AKT signaling pathway.

The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high-fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway.

The learning curve for laparoscopic pancreaticoduodenectomy by a proficient laparoscopic surgeon: a retrospective study at a single center.

BACKGROUND: To explore the learning curve of single center laparoscopic pancreaticoduodenectomy (LPD) and evaluate the safety and efficacy of the operation at different stages. METHODS: A detailed review was conducted on the clinical data of 120 cases of laparoscopic pancreatoduodenectomy performed by the same surgeon between June 2018 and June 2022. Cases that did not provide insights into the learning curve of the procedure were excluded. The cumulative sum (CUSUM) analysis and the best fitting curve methods were employed to delineate the learning curve based on operation time and intraoperative blood loss. The study further evaluated the number of surgeries required to traverse the learning curve. Outcome measures, including operation time, intraoperative blood loss, length of stay, complications, and other relevant indicators, were extracted and compared across different phases of the learning curve. RESULT: The maximum turning point of the fitting curve was found in 35 cases by the cumulative sum method of operation time, after which the learning curve could be considered to have passed. The fitting curve obtained by the cumulative sum method of intraoperative blood loss was stable in 30 cases and proficient in 60 cases, which was basically consistent with the fitting curve of operation time. Taking 35 cases as the boundary, the learning curve is divided into learning improvement stage and mastering stage. There was no statistical significance in the general data of the two stage patients (P > 0.05). Hospitalization days decreased from 19 to 15 days (P < 0.05);Pancreatic fistula decreased from 20.0% of grade B and 8.6% of grade C to 7.1% of grade B and 3.5% of grade C (P < 0.05), and the operative time decreased from (376.9 ± 48.2) minutes to (294.4 ± 18.7) minutes (P < 0.05). Intraoperative blood loss decreased from 375 to 241 ml (P < 0.05). CONCLUSION: Thirty-five patients with LPD can reach the proficiency stage and the perioperative indexes can be improved.

Intraductal papillary mucinous neoplasm of the biliary tract in the caudate lobe of the liver: a case report and literature review.

An intraductal papillary mucinous neoplasm of the biliary tract (BT-IPMN) in the caudate lobe of the liver is a rare tumor originating from the bile duct. Approximately 40% of the intraductal papillary neoplasms of the biliary tract (IPNB) secrete mucus and can grow in the intrahepatic or extrahepatic bile ducts. A 65-year-old woman presented with recurrent episodes of right upper pain. She developed her first episode 8 years ago, which resolved spontaneously. The frequency of symptoms has increased in the last 2 years. She underwent laparoscopic hepatectomy and choledochal exploration and was pathologically diagnosed with a rare BT-IPMN of the caudate lobe after admission. Here, we review studies on IPNB cases and systematically describe the pathological type, diagnosis, and treatment of IPNB to provide a valuable reference for hepatobiliary surgeons in the diagnosis and treatment of this disease.

Prediction of small molecule drug-miRNA associations based on GNNs and CNNs.

MicroRNAs (miRNAs) play a crucial role in various biological processes and human diseases, and are considered as therapeutic targets for small molecules (SMs). Due to the time-consuming and expensive biological experiments required to validate SM-miRNA associations, there is an urgent need to develop new computational models to predict novel SM-miRNA associations. The rapid development of end-to-end deep learning models and the introduction of ensemble learning ideas provide us with new solutions. Based on the idea of ensemble learning, we integrate graph neural networks (GNNs) and convolutional neural networks (CNNs) to propose a miRNA and small molecule association prediction model (GCNNMMA). Firstly, we use GNNs to effectively learn the molecular structure graph data of small molecule drugs, while using CNNs to learn the sequence data of miRNAs. Secondly, since the black-box effect of deep learning models makes them difficult to analyze and interpret, we introduce attention mechanisms to address this issue. Finally, the neural attention mechanism allows the CNNs model to learn the sequence data of miRNAs to determine the weight of sub-sequences in miRNAs, and then predict the association between miRNAs and small molecule drugs. To evaluate the effectiveness of GCNNMMA, we implement two different cross-validation (CV) methods based on two different datasets. Experimental results show that the cross-validation results of GCNNMMA on both datasets are better than those of other comparison models. In a case study, Fluorouracil was found to be associated with five different miRNAs in the top 10 predicted associations, and published experimental literature confirmed that Fluorouracil is a metabolic inhibitor used to treat liver cancer, breast cancer, and other tumors. Therefore, GCNNMMA is an effective tool for mining the relationship between small molecule drugs and miRNAs relevant to diseases.

LHPP Inhibits the Viability, Migration, and Proliferation of PDAC Cells and Significantly Affects the Expression of SDC1 and S100p.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor response to chemotherapy and an extremely poor prognosis. Recent studies have revealed that phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) can inhibit the growth of various cancers. Therefore, the current study was conducted to investigate the antitumor effects of LHPP in PDAC and to explore its mechanism using proteomics analysis. METHODS AND RESULTS: Immunohistochemical analysis of clinical samples demonstrated that LHPP expression levels were lower in tumor tissues compared to adjacent nontumor tissues. Moreover, multivariate COX regression analysis showed that LHPP expression level was an independent prognostic factor for the patients with PDAC. Patients with high LHPP expression had a better prognosis. The lentiviral vectors for normal control (NC), LHPP knockdown (KD), and LHPP overexpression (OE) were infected with BxPC-3 and PANC-1 cell lines. Cell counting kit-8 assay, Transwell assay, and flow cytometry analyses showed that LHPP overexpression significantly inhibited the cell viability, migration, and proliferation of BxPC-3 and PANC-1 cells. Moreover, xenograft tumor model demonstrated that LHPP overexpression inhibited xenograft tumor growth in vivo. Subsequently, proteins with significantly altered expression in BxPC-3 cells after lentivirus infection were detected using proteomics analyses. Interestingly, compared to the NC group, the expression of Syndecan 1 (SDC1) was significantly upregulated in the KD group, while that of S100P was significantly downregulated in the OE group. CONCLUSION: LHPP might emerge as an important target for delaying the advancement of PDAC, thereby providing a novel therapeutic approach for the treatment of PDAC.

Short-term clinical outcomes of laparoscopic duodenum-preserving pancreatic head resection for the management of pancreatic-head cystic neoplasms.

BACKGROUND: In this study, we aimed to investigate the short-term clinical outcomes of laparoscopic duodenum-preserving pancreatic-head resection (LDPPHR) for the management of pancreatic-head cystic neoplasms. METHODS: This retrospective study included 60 patients who were treated with pancreatic-head cystic neoplasms at the Shandong Provincial Hospital Affiliated to Shandong First Medical University from December 2019 to July 2022. RESULTS: No significant difference was found between the two groups in terms of the baseline and pathological characteristics of patients (P > 0.05). The postoperative exhaust time was shorter in the LDPPHR group compared with the laparoscopic pancreaticoduodenectomy (LPD) group (2 (2 and 4) vs. 4 (3 and 5) days; P = 0.003). No significant difference was found between the two groups in terms of operative time, estimated blood loss, intraoperative transfusion, hemoglobin levels on the first postoperative day, total bilirubin before discharge, direct bilirubin before discharge, postoperative hospital stay, postoperative pancreatic fistula, bile leakage, hemorrhage, peritoneal effusion, abdominal infection, delayed gastric emptying, interventional embolization hemostasis, reoperation, and 30-day readmission (P > 0.05). No conversion and 90-day mortality were found in the two groups. The LDPPHR group showed a higher 3-month postoperative PNI, 6-month postoperative TG and 6-month postoperative BMI than the LPD group (P < 0.05). CONCLUSIONS: Compared with LPD, LDPPHR can decrease the postoperative exhaust time of patients, improve the short-term postoperative nutritional status, and does not decrease the safety of the perioperative period.

Esophageal cancer-related gene 4 inhibits gastric cancer growth and metastasis by upregulating Krüppel-like factor 2 expression.

Background: There are a large number of people suffering from gastric cancer (GC) worldwide, so the study of biomarkers for GC is urgently needed. This study aimed to investigate the role of esophageal cancer-related gene 4 (ECRG4) in the growth, metastasis, and prognosis of GC and the possible underlying mechanism. Methods: The expression of ECRG4 was detected in GC tissues by quantitative polymerase chain reaction (PCR), Western blot, and immunohistochemistry. The relationships between ECRG4 expression and clinicopathological parameters of patients with GC were statistically analyzed, and Kaplan-Meier prognosis and survival curves of the patients were plotted. ECRG4 was overexpressed in the human gastric adenocarcinoma cell line (AGS) and human GC cell line 27 (HGC27), and the in vivo effects of ECRG4 overexpression on the growth, invasion, and metastasis of GC were analyzed and verified in nude mice. To identify the downstream transcription factors potentially regulated by ECRG4, ribonucleic acid (RNA) sequencing and differential gene expression analysis were performed on ECRG4-overexpressing cells. Quantitative PCR, Western blot, and immunohistochemistry were used to detect the expression of the downstream transcription factors targeted by ECRG4 in GC. Results: The ECRG4 mRNA and protein expression levels were low in GC tissues and were associated with a poor prognosis. Least absolute shrinkage and selection operator (LASSO) Cox regression and Kaplan-Meier survival analyses showed that patients with low ECRG4 expression had worse prognosis and survival. Overexpression of ECRG4 inhibited the proliferation, metastasis, and invasion of GC cells. RNA sequencing analysis showed that overexpression of ECRG4 induced the upregulation of Krüppel-like factor 2. Conclusions: Our findings show that ECRG4 promotes GC progression via Krüppel-like factor 2 signaling and highlight ECRG4 as a potential GC biomarker and therapeutic target.

Development and validation of a mitochondrial energy metabolism-related risk model in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and ranks third inmortality. Mitochondria are the energy manufacturers of cells. Disruption of mitochondrial energy metabolism pathways is strongly correlated with the onset and progression of HCC. Aberrant genes in mitochondrial energy metabolism pathways may represent a unique diagnostic and therapeutic targets that act as indicators for HCC. METHODS: Gene expression data from 374 HCC patients and 50 controls were acquired from TCGA database. A total of 188 mitochondrial energy metabolism-related genes (MMRGs) were obtained from KEGG PATHWAY database. A total of 368 patients with survival data were randomly split into training and validation groups in a 7: 3 ratio. Prognosis-related MMRGs were selected by univariate Cox and LASSO analyses. Kaplan-Meier and ROC curves were employed to analyze the model precision, whereas the validation set was used for model verification. Furthermore, clinical examinations, immune infiltration analysis, GSVA, and immunotherapy analysis were conducted in the high- and low-risk groups. Finally, the risk model was combined with the clinical variables of HCC patients to perform univariate and multivariate Cox regression analyses to obtain independent risk indicators and draw a nomogram. Therefore, we evaluated the accuracy of the predictions using calibration curves. RESULTS: A total of 6032 differentially expressed genes (DEGs) were detected in the HCC and control samples. After overlapping DEGs with 188 MMRGs, 42 mitochondrial energy metabolism-related DEGs (DEMMRGs) were identified. A 17 specific genes-based risk score model of HCC was created, which revealed effectiveness in each TCGA training and validation dataset. Moreover, patients categorized by risk scores exhibited distinct immune infiltration status, immunotherapy responsiveness, and functional properties. Finally, univariate and multivariate Cox regression analyses revealed that risk score and stage T were independent predictive variables. Based on the T stage and risk score, a nomogram for estimating the survival of HCC patients was created. The calibration curves demonstrated that the prediction model had a high level of accuracy. CONCLUSIONS: Our study constructed a mitochondrial energy metabolism-related risk model, that may be utilized to anticipate HCC prognosis and represent the immunological microenvironment of HCC.

Benchmark for establishment of organoids from gastrointestinal epithelium and cancer based on available consumables and reagents.

Gastrointestinal cancers are a public health problem that threatens the lives of human being. A good experimental model is a powerful tool to promote the uncovering pathogenesis and establish novel treatment methods. High-quality biomedical research requires experimental models to recapitulate the physiological and pathological states of their parental tissues as much as possible. Organoids are such experimental models. Organoids refer to small organ-like cellular clusters formed by the expansion and passaging of living tissues in 3D culture medium in vitro. Organoids are highly similar to the original tissues in terms of cellular composition, cell functions, and genomic profiling. Organoids have many advantages, such as short preparation cycles, long-term storage based on cryopreservation, and reusability. In recent years, researchers carried out the establishment of organoids from gastrointestinal mucosa and cancer tissues, and accumulated valuable experiences. In order to promote effective usage and further development of organoid-related technologies in the research of gastrointestinal diseases, this study proposes a benchmark based on utilization of available experimental consumables and reagents, which are involved in the key steps such as collection and pretreatment of biospecimen, organoid construction, organoid cryopreservation and recovery, growth status evaluation, and organoid quality control. We believe that the standard for the construction and preservation of organoids derived from human gastrointestinal epithelium and cancer tissues can provide an important reference for the majority of scientific researchers.

Prognostic analysis of radical resection for iCCAphl and iCCApps: A retrospective cohort study.

Backgroud: At present, there is no definitive conclusion about the relative prognostic factors on intrahepatic cholangiocarcinoma perihilar large duct type (iCCAphl) and iCCA peripheral small duct type (iCCApps). Aim of the study: To compare the prognoses of two different types of iCCA, and identify the independent risk factors affecting the long-term survival of patients undergoing radical resection for iCCA. Methods: This study included 89 patients with iCCA who underwent radical resection at the Department of Hepatobiliary Surgery of the East Yard of the Shandong Provincial Hospital between January 2013 and March 2022. According to the tumor origin, these patients were divided into the iCCAphl group (n = 37) and iCCApps group (n = 52). The prognoses of the two groups were compared using Kaplan-Meier analysis, whereas the independent risk factors of their prognoses were identified using Cox univariate and multivariate regression analyses. Results: In the iCCApps group, the independent risk factors for overall survival included diabetes history (p = 0.006), lymph node metastasis (p = 0.040), and preoperative carbohydrate antigen 19-9 (p = 0.035). In the iCCAphl group, the independent risk factors for overall survival included multiple tumors (p = 0.010), tumor differentiation grade (p = 0.008), and preoperative jaundice (p = 0.009). Conclusions: Among the iCCA patients who underwent radical resection, the long-term prognosis of iCCApps maybe better than that of iCCAphl. The prognoses of these two types of iCCA were affected by different independent risk factors.

A study on the diagnosis of the Helicobacter pylori coccoid form with artificial intelligence technology.

Background: Helicobacter pylori (H. pylori) is an important pathogenic microorganism that causes gastric cancer, peptic ulcers and dyspepsia, and infects more than half of the world's population. Eradicating H. pylori is the most effective means to prevent and treat these diseases. H. pylori coccoid form (HPCF) causes refractory H. pylori infection and should be given more attention in infection management. However, manual HPCF recognition on slides is time-consuming and labor-intensive and depends on experienced pathologists; thus, HPCF diagnosis is rarely performed and often overlooked. Therefore, simple HPCF diagnostic methods need to be developed. Materials and methods: We manually labeled 4,547 images from anonymized paraffin-embedded samples in the China Center for H. pylori Molecular Medicine (CCHpMM, Shanghai), followed by training and optimizing the Faster R-CNN and YOLO v5 models to identify HPCF. Mean average precision (mAP) was applied to evaluate and select the model. The artificial intelligence (AI) model interpretation results were compared with those of the pathologists with senior, intermediate, and junior experience levels, using the mean absolute error (MAE) of the coccoid rate as an evaluation metric. Results: For the HPCF detection task, the YOLO v5 model was superior to the Faster R-CNN model (0.688 vs. 0.568, mean average precision, mAP); the optimized YOLO v5 model had a better performance (0.803 mAP). The MAE of the optimized YOLO v5 model (3.25 MAE) was superior to that of junior pathologists (4.14 MAE, p < 0.05), no worse than intermediate pathologists (3.40 MAE, p > 0.05), and equivalent to a senior pathologist (3.07 MAE, p > 0.05). Conclusion: HPCF identification using AI has the advantage of high accuracy and efficiency with the potential to assist or replace pathologists in clinical practice for HPCF identification.

Inhibition of neuropilin-1 enhances the therapeutic effects of lenvatinib in suppressing cholangiocarcinoma cells via the c-Met pathway.

Neuropilin-1 (NRP-1) participates in the progression of cholangiocarcinoma (CCA) and lenvatinib is an approved tyrosine kinase inhibitor treating several other cancers. Our exploratory study reveals that the inhibitory activities of lenvatinib largely rely on the expression levels of NRP-1 in CCA cells, leading to the present study that aims to investigate whether inhibition of NRP-1 could enhance the effects of lenvatinib in suppressing CCA. By using stable transfected CCA cells depleted of NRP-1 and EG00229, a specific NRP-1 inhibitor, we examined cell proliferation, cell cycle distribution and apoptosis, and detected the expression of key molecules and the involvement of the c-Met pathway. Xenograft mouse models were employed to verify the in vitro results. NRP-1 depletion and EG00229 strengthened lenvatinib in inhibiting the proliferation and promoting the apoptosis of CCA cells, and their additive or synergistic effects were confirmed in animal models. Mechanistically, lenvatinib induced the activation of the c-Met pathway, while either NRP-1 depletion or EG00229 inhibited this activation, which could be stimulated by its ligand hepatocyte growth factor. NRP-1 inhibition resulted in a significant alteration in the expression/activation of downstream pathways and molecules, which are key factors regulating cell proliferation and apoptosis. In conclusion, the present results indicate that the inhibition of NRP-1 enhances the efficacy of lenvatinib via the c-Met pathway, and warrant further studies on the pharmacological utility of EG00229, particularly, in the combination of lenvatinib as a promising adjunct therapeutic strategy for combating CCA.

Prevalence and risk factors of Helicobacter pylori infection in Ningxia, China: comparison of two cross-sectional studies from 2017 and 2022.

OBJECTIVES: Helicobacter pylori (H. pylori) infection causes a variety of intragastric and extragastric diseases. Despite its decreasing global prevalence, it remains a major public health problem in many developing countries. This study aimed to understand the prevalence of H. pylori infection and its risk factors in five cities of the Ningxia Hui Autonomous Region, an area with high incidence of gastric cancer. METHODS: Cross-sectional studies were conducted in Ningxia from 2017 and 2022, to detect the prevalence of H. pylori using the 14C urea breath test. All participants completed a questionnaire that included demographics, personal habits, household economic characteristics, and previous health status. Multiple logistic regression analyses were used to identify independent factors for H. pylori infection. RESULTS: Our findings demonstrated that the prevalence of H. pylori infection in Ningxia decreased significantly from 60.3% in 2017 to 43.6% in 2022, with an increase in public awareness rate from 35.9% in 2017 to 68.5% in 2022. The lowest infection rate was found in Zhongwei and highest in Guyuan. The prevalence of H. pylori infection was higher among Hui ethnicity, farmers, individuals living in rural areas, individuals with lower income, low education, and those who consumed less fruit. Gallbladder, respiratory, cardiovascular and autoimmune diseases were not associated with H. pylori infection. CONCLUSIONS: The prevalence of H. pylori in Ningxia decreased in the past five years. Ethnicity, location, occupation, income, education, and consumption of fruits were independent risk factors for H. pylori infection in Ningxia. It was not associated with extra-gastric disease.

Potential prognosis index for m6A-related mRNA in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CHOL) is a malignant tumor that originates in the extrahepatic bile duct and can extend from the hilar region to the lower end of the common bile duct. The prognosis of CHOL patients is particularly poor; therefore, in this study, we screened mRNAs correlated with N6-methyladenosine (m6A) to construct a risk model for prognosis in CHOL. METHODS: The TCGA-CHOL dataset was applied to obtain and analyze the coexpression of 1281 m6A-related mRNAs, from which 14 were selected for further analysis through univariate proportional hazards (cox) regression analysis. Aryl hydrocarbon receptor interacting protein (AIP), CCAAT/enhancer binding protein beta (CEBPB), syndecan1 (SDC1), vacuolar protein sorting 25 homolog (VPS25) and syntaxin binding protein 2 (STXBP2) were then screened out through the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis to develop a precise m6A-related mRNA prognosis risk model (MRMRPM) with an area under curve (AUC) of 0.908 and 0.923 after 1 and 2 years, respectively. We divided the samples into high-risk and low-risk groups using the m6A-related mRNA prognosis risk model. RESULTS: Kaplan-Meier analysis indicated poor overall survival (OS) for the high-risk group. Two Gene Expression Omnibus (GEO) datasets (GSE89748 and GSE107943) were used to validate the risk model. The results of drug sensitivity and immune cell infiltration analysis showed that the risk model could serve as a prognosis index of potential immunotherapeutic characteristics and drug sensitivity. Furthermore, the proportion of resting dendritic cells and regulatory T cells was positively associated with an increased expression of four m6A-related mRNAs - AIP, CEBPB, SDC1, and VPS25 - in the high-risk CHOL group. CONCLUSIONS: Our findings suggest that this model can be a prognostic indicator for CHOL patients.

MCT4 Promotes Hepatocellular Carcinoma Progression by Upregulating TRAPPC5 Gene.

Purpose: Monocarboxylate transporter 4 (MCT4) is an important component of cancer cell glycolytic metabolism. It has been confirmed that MCT4 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues and is significantly associated with poor prognosis of HCC patients. However, research on its downstream molecules that affect HCC is still insufficient. The aim of current research was to investigate the MCT downstream molecule and its role of in HCC development. Patients and Methods: After MCT4 expression was knocked down by RNA interference, RNA sequencing and quantitative real-time PCR were used to screen for differentially expressed genes in an HCC cell line (HCCLM3). Immunohistochemistry in HCC tissue microarray was carried out to evaluate the Trafficking Protein Particle Complex Subunit 5 (TRAPPC5) expression. Cell proliferation, migration, and invasion were evaluated by CCK-8 assay, colony formation assay, transwell and wound-healing test, respectively. Xenograft experiment was employed to investigate the function of TRAPPC5 on tumor growth in vivo. Related signaling pathway proteins were evaluated by Western blot. Results: TRAPPC5 expression was significantly downregulated after knocking down of MCT4 in HCCLM3. TRAPPC5 was highly expressed in HCC tissues, and it could enhance the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process of HCC cells. In vivo experiment showed that TRAPPC5 could promote HCC tumorigenesis. Conclusion: In the process of MCT4 affecting the progression of HCC, TRAPPC5 is one of the most important related molecules. TRAPPC5 suppression could significantly reduce HCC cell proliferation, migration and invasion and could serve as a therapeutic target in HCC.

Emphasizing the importance of successful eradication of Helicobacter pylori on initial treatment.

Helicobacter pylori (H. pylori) infection is the most important risk factor for gastric cancer and plays an initiating role in the development of intestinal-type gastric cancer. Eradication of H. pylori significantly reduces the incidence and mortality of gastric cancer. International expert consensus recommends eradication treatment for all infected individuals unless competing considerations. However, large-scale H. pylori eradication treatments have led to increasing rates of resistance to multiple antibiotics, together with factors such as coccoid transformation, host CYP2C19 gene polymorphisms, and inappropriate treatment regimens, resulting in a gradual decline in H. pylori eradication rates. Currently, empirical and repeated eradication of H. pylori treatment is common in clinical practice, which will certainly lead to a further increase in antibiotic resistance, resulting in a great waste of medical resources and an increased psychological burden on patients and their relatives. Therefore, successful eradication of H. pylori on initial treatment should be given high priority, and the implementation of personalized treatment is essential.

The aberrant upregulation of exon 10-inclusive SREK1 through SRSF10 acts as an oncogenic driver in human hepatocellular carcinoma.

Deregulation of alternative splicing is implicated as a relevant source of molecular heterogeneity in cancer. However, the targets and intrinsic mechanisms of splicing in hepatocarcinogenesis are largely unknown. Here, we report a functional impact of a Splicing Regulatory Glutamine/Lysine-Rich Protein 1 (SREK1) variant and its regulator, Serine/arginine-rich splicing factor 10 (SRSF10). HCC patients with poor prognosis express higher levels of exon 10-inclusive SREK1 (SREK1L). SREK1L can sustain BLOC1S5-TXNDC5 (B-T) expression, a targeted gene of nonsense-mediated mRNA decay through inhibiting exon-exon junction complex binding with B-T to exert its oncogenic role. B-T plays its competing endogenous RNA role by inhibiting miR-30c-5p and miR-30e-5p, and further promoting the expression of downstream oncogenic targets SRSF10 and TXNDC5. Interestingly, SRSF10 can act as a splicing regulator for SREK1L to promote hepatocarcinogenesis via the formation of a SRSF10-associated complex. In summary, we demonstrate a SRSF10/SREK1L/B-T signalling loop to accelerate the hepatocarcinogenesis.