Potential Role of the Anammoxosome in the Adaptation of Anammox Bacteria to Salinity Stress.

The underlying adaptative mechanisms of anammox bacteria to salt stress are still unclear. The potential role of the anammoxosome in modulating material and energy metabolism in response to salinity stress was investigated in this study. The results showed that anammox bacteria increased membrane fluidity and decreased mechanical properties by shortening the ladderane fatty acid chain length of anammoxosome in response to salinity shock, which led to the breakdown of the proton motive force driving ATP synthesis and retarded energy metabolism activity. Afterward, the fatty acid chain length and membrane properties were recovered to enhance the energy metabolic activity. The relative transmission electron microscopy (TEM) area proportion of anammoxosome decreased from 55.9 to 38.9% under salinity stress. The 3D imaging of the anammox bacteria based on Synchrotron soft X-ray tomography showed that the reduction in the relative volume proportion of the anammoxosome and the concave surfaces was induced by salinity stress, which led to the lower energy expenditure of the material transportation and provided more binding sites for enzymes. Therefore, anammox bacteria can modulate nitrogen and energy metabolism by changing the membrane properties and morphology of the anammoxosome in response to salinity stress. This study broadens the response mechanism of anammox bacteria to salinity stress.

Role of CCR1/5/7 in hepatocellular carcinoma: a study on prognostic evaluation, molecular subtyping, and association with immune infiltration.

This study aims to assess the prognostic value of the C-C motif chemokine receptor (CCR) gene family in hepatocellular carcinoma (HCC) and its relationship with immune infiltration and molecular subtypes of HCC. The evaluation of the GSE14520 dataset and TCGA database confirmed the prognostic significance of CCR. Building upon the correlation between CCR1, CCR5, and CCR7 and favorable prognosis, we further validated the prognostic importance of CCR1, CCR5, and CCR7 in ICGC database and an independent cohort from Guangxi autonomous region. Then, we constructed a risk prognosis model. Additionally, we observed significant positive correlations between CCR1, CCR5, and CCR7 and the infiltration of B cells, T cells, and macrophages in HCC. Subsequently, we conducted CCK assays, Transwell assays, and colony formation assays to evaluate the molecular biological functions of CCR1, CCR5, and CCR7. These experiments further confirmed that upregulation of CCR1, CCR5, and CCR7 can individually inhibit the proliferation, migration, and stemness of HCC cells. By analyzing the relationship between expression levels and tumor mutation frequency, we discovered that patients with high CCR1 expression were more likely to be classified as non-proliferative HCC. Similar conclusions were observed for CCR5 and CCR7. The association of CCR1, CCR5, and CCR7 with the molecular subtypes of HCC suggests that they may serve as intermediary molecules linking immune status and molecular subtypes in HCC. In summary, CCR1, CCR5, and CCR7 have the potential to serve as prognostic biomarkers for HCC and regulate HCC progression by influencing immune cell infiltration.

Analysis of clinicopathologic and imaging features of dual-phenotype hepatocellular carcinoma.

Dual-phenotype hepatocellular carcinoma (DPHCC) is a new subtype of hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between the computerized tomography scan (CT) imaging and clinicopathologic features of DPHCC. The CT imaging and clinicopathologic data of 97 HCC cases who underwent radical resection were collected retrospectively. The CT imaging feature was evaluated by the ratio of the average CT value of tumor to liver (TLR) in the plain scan, arterial, portal vein and delayed phases. The association between CT imaging and clinicopathologic features was analyzed using the t-test or chi-square test. Univariate and multivariate recurrence-free survival (RFS) analysis and overall survival (OS) were performed. The positive rates of cytokeratin 7 (CK7) and CK19 were 35.1% and 20.6% respectively. The positive rate of CK19 was significantly higher in cases with age < 47 years (P = 0.005), tumor diameter > 4 cm (P = 0.016) or AFP ≥ 400 ng/ml (P = 0.007). The TLR in the portal vein phase was significantly lower in CK19 positive group (P = 0.024). The recurrence risk was significantly higher in cases with CK19 positive (HR: 2.17, 95% CI 1.16 to 4.04, P = 0.013), tumor diameter > 4 cm (HR: 2.05, 95% CI 1.11 to 3.78, P = 0.019), AFP ≥ 400 ng/ml (HR: 2.50, 95% CI 1.37 to 4.54, P = 0.002) or CA199 ≥ 37 U/ml (HR: 2.23, 95% CI 1.12 to 4.42, P = 0.020). However, imaging features, pathological subtype, CK7 or CK19 expression were not significantly related to HCC OS in the univariate and multivariate analysis (all P > 0.05). The expression of CK19 may be associated with the enhancement feature of the portal vein phase CT image, and CK19 positive may suggest a worse RFS.

The secreted feruloyl esterase of Verticillium dahliae modulates host immunity via degradation of GhDFR.

Feruloyl esterase (ferulic acid esterase, FAE) is an essential component of many biological processes in both eukaryotes and prokaryotes. This research aimed to investigate the role of FAE and its regulation mechanism in plant immunity. We identified a secreted feruloyl esterase VdFAE from the hemibiotrophic plant pathogen Verticillium dahliae. VdFAE acted as an important virulence factor during V. dahliae infection, and triggered plant defence responses, including cell death in Nicotiana benthamiana. Deletion of VdFAE led to a decrease in the degradation of ethyl ferulate. VdFAE interacted with Gossypium hirsutum protein dihydroflavanol 4-reductase (GhDFR), a positive regulator in plant innate immunity, and promoted the degradation of GhDFR. Furthermore, silencing of GhDFR led to reduced resistance of cotton plants against V. dahliae. The results suggested a fungal virulence strategy in which a fungal pathogen secretes FAE to interact with host DFR and interfere with plant immunity, thereby promoting infection.

Sarcosine dehydrogenase as an immune infiltration-associated biomarker for the prognosis of hepatocellular carcinoma.

This study was aimed to investigate the prognostic value and clinical significance of sarcosine dehydrogenase (SARDH) in hepatocellular carcinoma (HCC) and to explore the underlying mechanisms. The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), HPA and CPTAC databases were adopted to analyze the expression of SARDH mRNA and protein between normal liver tissue and HCC, and examine their relationship with clinicopathological features. Kaplan-Meier analysis, Cox regression, as well as nomogram were adopted to explore the prognostic value of SARDH in HCC. Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia (KEGG) together with Gene Set Enrichment Analysis (GSEA) were adopted to analyze the molecular mechanisms and biological functions of SARDH in HCC; while MethSurv, STRING, GeneMANIA, TIMER database data and single-sample gene set enrichment analysis (ssGSEA) algorithm were used for other bioinformatic analysis. Furthermore, immunohistochemistry was used to verify the expression of SARDH. Compared to normal liver tissue, SARDH expression was markedly lower in HCC. A lower SARDH expression was linked with Pathologic T stage (T3&T4), pathologic stage (Stage III&IV), and histologic grade (G3&4), which further indicates worse prognosis. Besides, results of bioinformatic analysis proved that SARDH expression was correlated with immune infiltration. In addition, SARDH hypermethylation was related to a poorer prognosis. SARDH expression was related to several key genes in the Ferroptosis pathway.

Investigating the prognostic and predictive value of the type II cystatin genes in gastric cancer.

BACKGROUND: Accumulating evidence indicates that type II cystatin (CST) genes play a pivotal role in several tumor pathological processes, thereby affecting all stages of tumorigenesis and tumor development. However, the prognostic and predictive value of type II CST genes in GC has not yet been investigated. METHODS: The present study evaluated the expression and prognostic value of type II CST genes in GC by using The Cancer Genome Atlas (TCGA) database and the Kaplan-Meier plotter (KM plotter) online database. The type II CST genes related to the prognosis of GC were then screened out. We then validated the expression and prognostic value of these genes by immunohistochemistry. We also used Database for Annotation, Visualization, and Integrated Discovery (DAVID), Gene Multiple Association Network Integration Algorithm (GeneMANIA), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), nomogram, genome-wide co-expression analysis, and other bioinformatics tools to analyze the value of type II CST genes in GC and the underlying mechanism. RESULTS: The data from the TCGA database and the KM plotter online database showed that high expression of CST2 and CST4 was associated with the overall survival (OS) of patients with GC. The immunohistochemical expression analysis showed that patients with high expression of CST4 in GC tissues have a shorter OS than those with low expression of CST4 (HR = 1.85,95%CI: 1.13-3.03, P = 0.015). Multivariate Cox regression analysis confirmed that the high expression level of CST4 was an independent prognostic risk factor for OS. CONCLUSIONS: Our findings suggest that CST4 could serve as a tumor marker that affects the prognosis of GC and could be considered as a potential therapeutic target for GC.

Hepatic Artery Infusion Chemotherapy Sequential Hepatic Artery Embolization Combined with Operation in the Treatment of Recurrent Massive Hepatocellular Carcinoma Achieved Pathological Complete Response: A Case Report.

Hepatocellular carcinoma (HCC) recurrence, which encompasses both true recurrence resulting from cancer spread and de novo tumors developing within the same cancer-prone liver, presents a complication in approximately 70% of cases within a 5-year timeframe. The efficacy of neoadjuvant therapy for recurrence after hepatectomy for hepatocellular carcinoma is still unclear. We report a case of recurrent massive advanced hepatocellular carcinoma with pathological complete remission was treated by continuous hepatic arterial infusion chemotherapy (HAIC) and sequential transcatheter arterial embolization (TAE) combined with secondary operation. One month after resection, the patient recurred (massive type 141mm×76mm). After 4 times of HAIC sequential TAE conversion therapy, the tumor shrank significantly (70mm×29mm), alpha-fetoprotein(AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels decreased significantly, residual liver volume[left half liver accounted for 39.85% of standard liver volume(left half liver + right anterior lobe) accounted for 80.17% of standard liver volume] and Indocyanine green 15-minute retention(ICG R15 8.0%) complies with surgical requirement.The second operation was performed, and the tumor was completely resected after hepatic blood flow occlusion Requirement. The postoperative pathological results showed complete remission (PCR) of the tumor, and no recurrence was found during the follow-up of 16 months. In this case, HAIC sequential TAE conversion therapy has good short-term effect on patients with postoperative recurrence of hepatocellular carcinoma, tumor burden is significantly reduced, the second surgery pathology achieves complete remission, safety and tolerance, it is worthy of study and promotion.

A radiomics model based on magnetic resonance imaging to predict cytokeratin 7/19 expression and liver fluke infection of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. HCC with liver fluke infection could harbor unique biological behaviors. This study was aimed at investigating radiomics features of HCC with liver fluke infection and establishing a model to predict the expression of cytokeratin 7 (CK7) and cytokeratin 19 (CK19) as well as prognosis at the same time. A total of 134 HCC patients were included. Gadoxetic acid-enhanced magnetic resonance imaging (MRI) images of all patients were acquired. Radiomics features of the tumor were extracted and then data dimensionality was reduced. The radiomics model was established to predict liver fluke infection and the radiomics score (Radscore) was calculated. There were 11 features in the four-phase combined model. The efficiency of the combined model increased significantly compared to each single-phase MRI model. Radscore was an independent predictor of liver fluke infection. It was also significantly different between different expression of CK7/ CK19. Meanwhile, liver fluke infection was associated with CK7/CK19 expression. A cut-off value was set up and all patients were divided into high risk and low risk groups of CK7/CK19 positive expression. Radscore was also an independent predictor of these two biomarkers. Overall survival (OS) and recurrence free survival (RFS) of negative liver fluke infection group were significantly better than the positive group. OS and RFS of negative CK7 and CK19 expression were also better, though not significantly. Positive liver fluke infection and CK19 expression prediction groups harbored significantly worse OS and RFS, survival of positive CK7 expression prediction was unsatisfying as well. A radiomics model was established to predict liver fluke infection among HCC patients. This model could also predict CK7 and CK19 expression. OS and RFS could be foreseen by this model at the same time.

Outer dynein arm docking complex subunit 2 polymorphism rs7893462 modulates hepatocellular carcinoma susceptibility and can serve as an overall survival biomarker for hepatitis B virus-related hepatocellular carcinoma after hepatectomy: a cohort study with a long-term follow-up.

BACKGROUND: Genetic variants of outer dynein arm docking complex subunit 2 (ODAD2) have been reported to be closely associated with primary ciliary dyskinesia and colorectal cancer in previous studies, but the association of genetic variants of ODAD2 with hepatocellular carcinoma (HCC) has not been reported. METHODS: We enrolled 80 healthy subjects and 468 Guangxi hepatitis B virus (HBV)-related HCC patients in this study. A case-control study method was used to explore the association of different ODAD2-rs7893462 genotypes with hepatocarcinogenesis. A comprehensive survival analysis was used to explore the association of rs7893462 with the prognosis of HBV-related HCC in Guangxi. RESULTS: Through a case-control study, we observed that patients carrying the G allele of rs7893462 had a markedly increased susceptibility to hepatocarcinogenesis (odds ratio = 1.712, 95% confidence interval = 1.032-2.839, P = 0.037). We found that there were significant prognosis differences among three different genotypes of rs7893462. Nomogram analysis suggested that the contribution of rs7893462 polymorphisms to the prognosis of HBV-related HCC was second only to the BCLC stage. Stratified survival analysis suggested that the AG genotype of rs7893462 was an independent prognostic risk factor for HBV-related HCC. Joint effect survival analysis also observed that the AG genotype of rs7893462 combined with clinical parameters could significantly identify HBV-related HCC patients with different prognostic outcomes more accurately, and the AG genotype was also observed to be independent of clinical factors in HBV-related HCC survival. CONCLUSION: The ODAD2-rs7893462 polymorphisms can be used as an independent prognostic indicator of HBV-related HCC overall survival and are significantly associated with susceptibility to hepatocarcinogenesis.

RAD51AP1 as an Immune-Related Prognostic Biomarker and Therapeutic Response Predictor in Hepatocellular Carcinoma.

Background: RAD51 associated protein 1 (RAD51AP1) is shown to regulate cell proliferation and cancer progression. However, the immune-infiltrating correlation and the therapeutics guidance of RAD51AP1 in hepatocellular carcinoma (HCC) still need further investigation. Methods: In this study, comprehensive bioinformatic analysis of RAD51AP1 on differential expression, clinicopathologic correlation, prognostic value, and function enrichment were performed in The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO; GSE14520 and GSE76427), and International Cancer Genome Consortium (ICGC) datasets. Besides, the Guangxi cohort containing 50 pairs HCC and adjacent non-cancerous samples from First Affiliated Hospital of Guangxi Medical University was served as validation cohort. Moreover, we explored the predictive value of RAD51AP1 to therapeutics response and its underlying correlation with HCC immunoinfiltration. Results: RAD51AP1 was significantly overexpressed in HCC tissues and had a high diagnostic value of HCC. The shorter survival time and poorer clinical features were showed when RAD51AP1 upregulated, and then a nomogram featuring RAD51AP1 expression and other clinicopathologic factors was established to predict prognosis. In CIBERSORT analysis, higher T cells follicular helper but lower T cells CD4+ memory resting infiltration levels were exhibited when RAD51AP1 upregulated. The ssGSEA analysis demonstrated that high-RAD51AP1 expression subgroup had higher macrophages, Th2 and Treg cells infiltration levels, but lower type II IFN response function. Furthermore, high-RAD51AP1 expression subgroup exhibited the upregulated expression levels of immune-related checkpoint genes, but lower IPS and TIDE scores which suggested a possibly better immunotherapy response. The drug sensitivity analysis showed the high-expression subgroup may be more susceptible to Bexarotene, Doxorubicin, Gemcitabine and Tipifarnib. Conclusion: Taken together, RAD51AP1 is a potential diagnostic and prognostic biomarker. It may be related to the immunosuppressive microenvironment and could be an underlying HCC treatment strategy. However, the conclusions still require further validation studies.

Recent advancement in integrating artificial intelligence and information technology with real-world data for clinical decision-making in China: A scoping review.

OBJECTIVE: Striking innovations and advancements have been achieved with the use of artificial intelligence and healthcare information technology being integrated into clinical real-world data. The current scoping review aimed to provide an overview of the current status of artificial intelligence-/information technology-based clinical decision support tools in China. METHODS: PubMed/MEDLINE, Embase, China National Knowledge Internet, and Wanfang data were searched for both English and Chinese literature. The gray literature search was conducted for commercially available tools. Original studies that focused on clinical decision support tools driven by artificial intelligence or information technology in China and were published between 2010 and February 2022 were included. Information extracted from each article was further synthesized by themes based on three types of clinical decision-making. RESULTS: A total of 37 peer-reviewed publications and 13 commercially available tools were included in the final analysis. Among them, 32.0% were developed for disease diagnosis, 54.0% for risk prediction and classification, and 14.0% for disease management. Chronic diseases were the most popular therapeutic areas of exploration, with particular emphasis on cardiovascular and cerebrovascular diseases. Single-center electronic medical records were the mainstream data sources leveraged to inform clinical decision-making, with internal validation being predominately used for model evaluation. CONCLUSIONS: To effectively promote the extensive use of real-world data and drive a paradigm shift in clinical decision-making in China, multidisciplinary collaboration of key stakeholders is urgently needed.

Robust analysis of a novel PANoptosis-related prognostic gene signature model for hepatocellular carcinoma immune infiltration and therapeutic response.

PANoptosis, an interplay between pyroptosis, apoptosis, and necroptosis, is deeply involved in cancer development and immunity. However, the influence of PANoptosis in hepatocellular carcinoma (HCC) remains to be further investigated. The differentially expressed PANoptosis-related genes (PANRGs) was screened in The Cancer Genome Atlas (TCGA) database. Accordingly, mutation, bioinformatics, and consensus clustering analyses were performed. Then, a prognostic risk model was developed by least absolute shrinkage and selection operator (LASSO) Cox regression. Furthermore, the prognostic value, immunity correlation and therapeutic response prediction ability of risk model were explored. A total of 18 PANRGs were differently expressed in the TCGA-HCC cohort and were mainly involved in cancer- and cell death-related signal pathways. Using unsupervised clustering method, we identified two PANRGs-mediated clustering patterns. The remarkable differences between the two clusters on overall survival (OS) and clinical features were demonstrated respectively. Based on the five-gene prognostic risk model, the calculated PANRG-scores were used to categorize the subgroups as high- and low-risk. Notably, the high-risk subgroup had a dismal prognosis and exhibited much lower immune infiltration levels of mast cells, nature killer cells and pDCs, but higher levels of aDCs, iDCs and Treg cells than those in the low-risk subgroup. Furthermore, we constructed a reliable nomogram combining clinical traits and PANRG-score to predict the OS of HCC patients. The significantly negative correlation between PANoptosis and tumor mutation burden (TMB), ferroptosis were revealed. In drug sensitivity analysis, the high-risk subgroup had a considerably lower TIDE score, suggesting a preferable response to immunotherapy, and may be more sensitive to Tipifarnib, Imatinib, Doxorubicin, and Gemcitabine. The upregulated mRNA expressions of FADD were validated in 16 paired HCC tissues of Guangxi cohort. Based on PANoptosis-related genes, an integrated risk signature was constructed to provide a roadmap for patient stratification and predict HCC patient's prognosis. The patients with the higher PANRG-score may carry a dismal survival and relatively low immune infiltration, but a potential better immunotherapy response. Therefore, future HCC therapy perspectives should emphasize the setting of PANoptosis to achieve a personalized, practicable and effective therapeutic regimen.

Genome-wide RNA-sequencing dataset reveals AC096751.1 sever as a novel prognostic long non-coding RNA and its potential molecular mechanisms in patients with colon adenocarcinoma.

Objective: Through data analysis, we observed that AC096751.1 is markedly imbalance between colon adenocarcinoma (COAD) cancer and paracancerous tissues. However, the prognostic value and potential molecular mechanism of AC096751.1 in COAD are still unclear. Methods: Whole genome RNA-sequencing datasets of The Cancer Genome Atlas (TCGA) COAD cohort were collected into current study, comprehensive survival analysis and bioinformatics function enrichment analysis approaches were apply to explore the clinical outcome and molecular mechanisms of AC096751.1 in COAD. Results: In current study, we found that AC096751.1 is markedly down-regulated in COAD cancer tissues (log2 fold change =2.303, P<0.0001, false discovery rate <0.0001), and can be serve as a biomarker to distinguish COAD cancer and paracancerous tissues [area under curve=0.9518, 95% confidence interval (CI)=0.9261-0.9776]. Survival analysis suggests that low expression of AC096751.1 is connected with poor clinical outcome of COAD, and can serve as a novel prognostic indicator (log-rank P=0.016, adjusted P=0.005, hazard ratio=0.548, 95% CI=0.360-0.836). Bioinformatics function enrichment analysis suggests that the molecular mechanism of AC096751.1 in COAD may include participation in cell adhesion, cell proliferation, mitogen-activated protein kinase kinase (MAPKK), MAPK, janus-activated kinase-singal transducers and activators of transcriprion cascade, Erk1 and Erk 2 cascade, and nuclear factor-kappa B pathway. Tumor microenvironment and immune infiltration analysis indicates that COAD patients with different AC096751.1 expression have significant variation in tumor immune background. Conclusion: The present study found that AC096751.1 is significantly differentially expressed in COAD and can be serve as a novel prognostic biomarker.

SART3, regulated by p53, is a biomarker for diagnosis, prognosis and immune infiltration in hepatocellular carcinoma.

OBJECTIVE: This study aimed to investigate the role of squamous cell carcinoma antigen recognized by T cells 3 (SART3) in hepatocellular carcinoma (HCC). METHODS: SART3 expression and prognostic value were analyzed in TCGA and GEO datasets. The diagnostic value and prognostic significance of SART3 were determined using immunohistochemistry in the Guangxi cohort. The whole-exome mutation spectrum of SART3 was analyzed in high and low expression groups in both TCGA and Guangxi cohorts. The biological functions of the SART3 gene were validated through in vitro experiments using small interfering RNA technology to downregulate SART3 expression in HCC cell lines. RESULTS: SART3 expression was significantly higher in HCC tissues than in adjacent noncancerous liver tissues in TCGA, GEO and Guangxi cohorts. High expression of SART3 was significantly associated with poor prognosis in HCC patients. In TCGA and Guangxi cohorts, the expression of SART3 in the TP53 mutation group was significantly higher than that in the non-mutation group. Downregulation of SART3 expression significantly inhibited the migration and proliferation of HCC cells. SART3 may be involved mainly in immune infiltration of Th2 cells and macrophages in HCC. Additionally, SART3 can upregulate the expression of immune checkpoints (PD-L1 and TIM-3) and predict potential therapeutic agents for HCC. CONCLUSION: The findings of this study demonstrate the diagnostic and prognostic value of SART3 in HCC. SART3 may be associated with immune infiltration of Th2 cells and macrophages in HCC, highlighting its potential role in the development and progression of HCC.

Challenges and Solutions in Implementing eSource Technology for Real-World Studies in China: Qualitative Study Among Different Stakeholders.

BACKGROUND: eSources consist of data that were initially documented in an electronic structure. Typically, an eSource encompasses the direct acquisition, compilation, and retention of electronic information (such as electronic health records [EHRs] or wearable devices), which serves to streamline clinical research. eSources have the potential to enhance the accuracy of data, promote patient safety, and minimize expenses associated with clinical trials. An opinion study published in September 2020 by TransCelerate outlined a road map for the future application of eSource technology and identified 5 key areas of challenges. The background of this study concerns the use of eSource technology in clinical research. OBJECTIVE: The aim of this study was to present challenges and possible solutions for the implementation of eSource technology in real-world studies by summarizing team experiences and lessons learned from an eSource record (ESR) project. METHODS: After initially developing a simple prototype of the ESR software that can be demonstrated systematically, the researchers conducted in-depth interviews and interacted with different stakeholders to obtain guidance and suggestions. The researchers selected 5 different roles for interviewees: regulatory authorities, pharmaceutical company representatives, hospital information department employees, medical system providers, and clinicians. RESULTS: After screening all consultants, the researchers concluded that there were 25 representative consultants. The hospital information department needs to implement many demands from various stakeholders, which makes the existing EHR system unable to meet all the demands of eSources. The emergence of an ESR is intended to divert the burden of the hospital information department from the enormous functional requirements of the outdated EHR system. The entire research process emphasizes multidisciplinary and multibackground expert opinions and considers the complexity of the knowledge backgrounds of personnel involved in the chain of clinical source data collection, processing, quality control, and application in real-world scenarios. To increase the readability of the results, the researchers classified the main results in accordance with the paragraph titles in "Use of Electronic Health Record Data in Clinical Investigations," a guide released by the US Food and Drug Administration. CONCLUSIONS: This study introduces the requirement dependencies of different stakeholders and the challenges and recommendations for designing ESR software when implementing eSource technology in China. Experiences based on ESR projects will provide new insights into the disciplines that advance the eSource research field. Future studies should engage patients directly to understand their experiences, concerns, and preferences regarding the implementation of eSource technology. Moreover, involving additional stakeholders, including community health care providers and social workers, will provide valuable insights into the challenges and potential solutions across various health care settings.

Case Report: A case of hepatocellular carcinoma with aberrant right hepatic artery treated with transarterial chemoembolization and infusion chemotherapy separately to bilobar lesion combining with systemic therapies and sequential hepatectomy.

Background: Hepatocellular carcinoma (HCC) with a dismal prognosis is the second most deadly malignancy globally. Surgery is believed to be a curative approach. Nevertheless, there is still a considerable probability of postoperative recurrence. Most patients present in advanced stages with a surgically and oncologically unresectable disease. Systemic medicines are increasingly important to downstage the disease and further improve survival. Case summary: A 67-year-old Chinese man with uncontrolled hepatitis B was discovered to have liver masses with abnormal serum vitamin K absence or antagonist-II (PIVKA-II) level during checkup for upper abdominal discomfort. Abdominal multiphase computerized tomography (CT) and gadoxetate disodium-enhanced magnetic resonance imaging (MRI) showed the bulky bilobar HCCs of Barcelona Clinic Liver Cancer stage B and China Liver Cancer Staging stage IIa. Furthermore, the aberrant right hepatic artery (RHA) originates from the superior mesenteric artery. Due to the location being adjacent to important vasculatures and massive size of the right-sided lesion, curative resection appears to be challenging. To achieve a favorable surgical margin, repeated hepatic arterial infusion chemotherapy (HAIC) was adopted through the variant RHA, while transarterial chemoembolization (TACE) was delivered to the left lobe to arrest tumor growth. Furthermore, sintilimab plus lenvatinib served as the sequential systemic therapy. After 5 months of conversion treatment, the partial response with a decreased serum PIVKA-II level was attained. The R0 hepatectomy was then performed without postoperative complications. The immunohistochemistry and next-generation sequencing results suggested that the two-side HCCs existing tumor heterogeneity were not completely consistent. The patient continues to be without evidence of disease. Conclusion: Our case highlights a favorable outcome in a man with bilobar bulky HCC after undergoing the comprehensive therapeutic schedule that includes personalized intervention and systemic drug therapy. In terms of conversion therapy, our case provides a secure and practical reference for managing unresectable bilobar HCC coexisting with the aberrant hepatic artery.

Comprehensive investigation of the prognostic values and molecular mechanisms of syntaxin binding protein 5 antisense RNA 1 in patients with colon adenocarcinoma based on RNA sequencing dataset.

Objective: The main purpose of this study is to perform a comprehensive investigation of the prognostic value and molecular mechanism of syntaxin binding protein 5 antisense RNA 1 (STXBP5-AS1) through the whole genome RNA sequencing data of the The Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) cohort. Methods: There were 438 COAD patients were fit into current study for survival analysis. Gene expression profiling interactive analysis 2.0, Database for Annotation, Visualization and Integrated Discovery v6.8, gene set enrichment analysis (GSEA) and connectivity map (CMap) are used to investigate the molecular mechanisms and targeted drugs of STXBP5-AS1 in COAD. Results: By comparing the expression level of tumor and non-tumor tissues, we found that STXBP5-AS1 was notablely down-regulated in COAD tumor tissues. Survival analysis suggested that low STXBP5-AS1 expression was significantly related to poor overall survival (OS) of COAD (log-rank P=0.035, adjusted P=0.005, HR=0.545, 95%CI=0.356-0.836). The enrichment analysis of STXBP5-AS1 co-expressed genes, GSEA and differentially expressed genes suggests that STXBP5-AS1 may play a part in COAD by regulating the following biological processes or pathways: cell junction, DNA replication, apoptosis, cell cycle, metastasis, tumor protein 53, Wnt, mTORC1, MCM, notch receptor 4, transforming growth factor beta receptor, and cGMP-PKG signaling pathway. CMap analysis was screened out four small molecule drugs (anisomycin, cephaeline, NU-1025 and quipazine) that may be used as STXBP5-AS1 targeted therapy drugs in COAD. The co-expression analysis of STXBP5-AS1 and immune cell gene signature indicated that STXBP5-AS1 was significantly related to immune cell gene set in normal intestinal tissues, but not in COAD tumor tissues. Conclusion: Our results revealed that STXBP5-AS1 is notablely down-regulated in COAD tumor tissues, and may act as a novel prognostic biomarker for COAD.

PUS1 May Be a Potential Prognostic Biomarker and Therapeutic Target for Hepatocellular Carcinoma.

Objective: The mechanisms of pseudouridine synthase (PUS) are not definite in hepatocellular carcinoma (HCC), the objective of this study is to investigate the effect of PUS genes in HCC. Materials and Methods: Differentially expressed and prognostic gene of PUS enzymes was identified based on The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. For the identified gene, pseudouridine synthase 1 (PUS1), was used for further research. The clinicopathological feature of PUS1 was analyzed by Student's t-test. Prognostic significance was explored by Kaplan-Meier (KM) analysis and Cox proportional hazards regression model. Receiver operating characteristic (ROC) curve was applied to appraise diagnostic and prognostic value. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Gene Set Enrichment Analysis (GSEA) were implemented to explore mechanism of PUS1. A Guangxi cohort was applied to verify differential expression. In vitro cell experiments were implemented to investigate the influence for proliferation, reactive oxygen species (ROS) level, migration, and invasion of HCC cells after a knockdown of PUS1. Results: PUS1 was significantly overexpressed in HCC tissues, and patients with high PUS1 were related to unpromising clinicopathological features. Survival analysis revealed high PUS1 expression was associated with a poor overall survival (OS) and 1 year-recurrence free survival (RFS), was an independent risk factor. Meanwhile, ROC curve showed that PUS1 had a diagnostic and prognostic significance to HCC. Functional enrichment analysis implied that PUS1 may be involved in metabolic pathways, mitochondrial function, non-alcoholic fatty liver disease (NAFLD), and some important carcinogenic pathways. Cell assays revealed that knockdown of PUS1 significantly constrained the migration, proliferation, invasion and improved the ROS level of HCC cells. Conclusion: PUS1 may be a prognostic biomarker and a underlying treatment target for HCC.

Comprehensive analysis of LILR family genes expression and tumour-infiltrating immune cells in early-stage pancreatic ductal adenocarcinoma.

Leucocyte immunoglobulin-like receptors (LILRs) are closely related to tumourigenesis, but their clinical value in early-stage pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy remains unknown. Kaplan-Meier and Cox proportional hazards regression models is used to investigate the association between LILR expression and prognosis in tumour biopsies and peripheral blood mononuclear cells. Risk score was calculated for each patient based on the prognostic model. DAVID, STRING, GeneMANIA, and GSEA were used to conduct pathway and functional analyses. The CIBERSORT algorithm is used to analyse tumour-infiltrating immune cells. Survival analysis showed that high levels of LILRA4 (p = 0.006) and LILRB4 (p = 0.04) were significantly associated with better overall survival. High levels of LILRA2 (p = 0.008) and LILRB4 (p = 0.038) were significantly associated with better relapse-free survival. JAK-STAT signalling pathway, regulation of T cell activation, regulation of the immune effector process, and tumour necrosis factor superfamily cytokine production were involved in molecular mechanisms that affected poor prognoses in the high-risk group in GSEA. CIBERSORT demonstrated that the high-risk group had significantly higher infiltrating fraction of memory-activated CD4 T cells and activated NK cells and lower fraction of resting dendritic cells and neutrophils. LILRB4 plays crucial roles in affecting the clinical outcomes of early-stage PDAC.

Massive Hepatocellular Carcinoma with Situs Inversus Totalis Achieved a Complete Response Following Camrelizumab Plus Apatinib and Combined with Two-Stage Hepatectomy: A Case Report.

Situs inversus totalis (SIT) is a rare congenital condition in which abdominal and thoracic organs are transposed from normal positions. Two-stage hepatectomy (TSH) combined with translational therapy for hepatocellular carcinoma (HCC) with SIT has been rarely reported. We report a 41-year-old man with giant hepatocellular carcinoma (71 mm × 55 mm × 51 mm) whose future residual liver (FLR) and standard liver volume (SLV) ratio at first diagnosis was 37.4%. Preoperative volume assessment of portal vein ligation (PVL) revealed inadequate hypertrophy of FLR. After a multidisciplinary group discussion (MDT), the patient decided to follow conversion therapy. Three months later, ratio of the FLR/SLV increased from 37.4% to 71% after operation, which met the surgical requirements. Second hepatectomy, right lobectomy was successful. There was no recurrence after six months of follow-up. In our case, conversion therapy appears to be effective in maintaining residual liver hyperplasia, reducing tumor load, and preventing tumor progression in patients with large HCC during TSH.