Pancreatic stellate cells: Key players in pancreatic health and diseases (Review).

As a pluripotent cell, activated pancreatic stellate cells (PSCs) can differentiate into various pancreatic parenchymal cells and participate in the secretion of extracellular matrix and the repair of pancreatic damage. Additionally, PSCs characteristics allow them to contribute to pancreatic inflammation and carcinogenesis. Moreover, a detailed study of the pathogenesis of activated PSCs in pancreatic disease can offer promise for the development of innovative therapeutic strategies and improved patient prognoses. Therefore, the present study review aimed to examine the involvement of activated PSCs in pancreatic diseases and elucidate the underlying mechanisms to provide a viable therapeutic strategy for the management of pancreas­related diseases.

Efficacy of the 'Five-Needle' method for pancreatojejunostomy in laparoscopic pancreaticoduodenectomy: an observational study.

Objective: The five-needle pancreato-intestinal anastomosis method is used in laparoscopic pancreaticoduodenectomy (LPD). The aim of this study was to explore the clinical efficacy and adverse reactions of this new surgical method and to provide a scientific reference for promoting this new surgical method in the future. Methods: A single-centre observational study was conducted to evaluate the safety and practicality of the five-needle method for pancreatojejunostomy in LPD surgeries. The clinical data of 78 patients who were diagnosed with periampullary malignancies and underwent LPD were collected from the 1st of August 2020 to the 31st of June 2023 at Lanzhou University First Hospital. Forty-three patients were treated with the 'Five-Needle' method (test groups), and 35 patients were treated with the 'Duct-to-Mucosa' method (control group) for pancreatojejunostomy. These two methods are the most commonly used and highly preferred pancreatointestinal anastomosis methods worldwide. The primary outcome was pancreatic fistula, and the incidence of which was compared between the two groups. Results: The incidence of pancreatic fistula in the five-needle method group and the duct-to-mucosa method group was not significantly different (25.6% vs. 28.6%, p=0.767). Additionally, there were no significant differences between the two groups in terms of intraoperative blood loss (Z=-1.330, p=0.183), postoperative haemorrhage rates (p=0.998), length of postoperative hospital stay (Z=-0.714, p=0.475), bile leakage rate (p=0.745), or perioperative mortality rate (p=0.999). However, the operative time in the 'Five-Needle' method group was significantly shorter than that in the 'Duct-to-Mucosa' method group (270 ± 170 mins vs. 300 ± 210 mins, Z=-2.336, p=0.019). Further analysis revealed that in patients with pancreatic ducts smaller than 3 mm, the incidence of pancreatic fistula was lower for the 'Five-Needle' method than for the 'Duct-to-Mucosa' method (12.5% vs. 53.8%, p=0.007). Conclusion: The five-needle method is safe and efficient for pancreatojejunostomy in LPD, and is particularly suitable for anastomosis in nondilated pancreatic ducts. It is a promising, valuable, and recommendable surgical method worthy of wider adoption.

Integrated analysis of scRNA-seq and bulk RNA-seq reveals that GPRC5A is an important prognostic gene in pancreatic cancer and is associated with B-cell Infiltration in pancreatic cancer.

Introduction: Pancreatic cancer (PC) is a malignancy with poor prognosis. This investigation aimed to determine the relevant genes that affect the prognosis of PC and investigate their relationship with immune infiltration. Methods: : First, we acquired PC single-cell chip data from the GEO database to scrutinize dissimilarities in immune cell infiltration and differential genes between cancerous and adjacent tissues. Subsequently, we combined clinical data from TCGA to identify genes relevant to PC prognosis. Employing Cox and Lasso regression analyses, we constructed a multifactorial Cox prognostic model, which we subsequently confirmed. The prognostic gene expression in PC was authenticated using RT-PCR. Moreover, we employed the TIMER online database to examine the relationship between the expression of prognostic genes and T and B cell infiltration. Additionally, the expression of GPRC5A and its correlation with B cells infiltration and patient prognosis were ascertained in tissue chips using multiple immune fluorescence staining. Results: The single-cell analysis unveiled dissimilarities in B-cell infiltration between cancerous and neighboring tissues. We developed a prognostic model utilizing three genes, indicating that patients with high-risk scores experienced a more unfavorable prognosis. Immune infiltration analysis revealed a significant correlation among YWHAZ, GPRC5A, and B cell immune infiltration. In tissue samples, GPRC5A exhibited substantial overexpression and a robust association with an adverse prognosis, demonstrating a positive correlation with B cell infiltration. Conclusion: GPRC5A is an independent risk factor in PC and correlated with B cell immune infiltration in PC. These outcomes indicated that GPRC5A is a viable target for treating PC.

A novel multidrug-resistant cell line from a Chinese patient with pancreatic ductal adenocarcinoma.

Chemotherapy resistance poses clinical challenges in pancreatic cancer treatment. Developing cell lines resistant to chemotherapy is crucial for investigating drug resistance mechanisms and identifying alternative treatment pathways. The genetic and biological attributes of pancreatic cancer depend on its aetiology, racial demographics and anatomical origin, underscoring the need for models that comprehensively represent these characteristics. Here, we introduce PDAC-X2, a pancreatic cancer cell line derived from Chinese patients. We conducted a comprehensive analysis encompassing the immune phenotype, biology, genetics, molecular characteristics and tumorigenicity of the cell line. PDAC-X2 cells displayed epithelial morphology and expressed cell markers (CK7 and CK19) alongside other markers (E-cadherin, Vimentin, Ki-67, CEA and CA19-9). The population doubling time averaged around 69 h. In vivo, PDAC-X2 cells consistently maintained their tumorigenicity, achieving a 100% tumour formation rate. Characterised by a predominantly tetraploid karyotype, this cell line exhibited a complex genetic markup. Notably, PDAC-X2 cells demonstrated resistance to multiple drugs, including gemcitabine, paclitaxel, 5-fluorouracil and oxaliplatin. In conclusion, PDAC-X2 presents an invaluable preclinical model. Its utility lies in facilitating the study of drug resistance mechanisms and the exploration of alternative therapeutic approaches aimed at enhancing the prognosis of this tumour type.

Current status of neoadjuvant immunotherapy for the treatment of gastric cancer.

Gastric cancer is one of the most prevalent malignant tumors worldwide, characterized by high incidence and mortality rates. At present, comprehensive surgical treatment has enhanced the prognosis of locally advanced gastric cancer patients significantly. However, the postoperative recurrence rate remains high, and the long-term survival for patients is sub-optimal. In recent years, immunotherapy has garnered extensive attention as an innovative approach to the treatment of gastric cancer. Indeed, multiple studies have validated its therapeutic effects in advanced gastric cancer patients, leading to its incorporation into treatment guidelines. Currently, researchers are exploring the application of immunotherapy in the neoadjuvant setting globally in order to further adjust and refine neoadjuvant immunotherapy regimens for gastric cancer. This article summarizes the research progress and controversies associated with neoadjuvant immunotherapy in gastric cancer, aiming to optimize clinical benefits for gastric cancer patients undergoing this treatment approach. The retrieval methods of this study encompassed databases such as PubMed, Google Scholar, Web of Science, clinicaltrials.gov, etc. The retrieved articles included guidelines, consensus, meta-analyses, clinical trials, and reviews related to locally advanced gastric cancer published up to January 2024.

Global burden of pancreatic cancer attributable to metabolic risks from 1990 to 2019, with projections of mortality to 2030.

OBJECTIVE: Metabolic risks play a key role in the progression of pancreatic cancer. This study aimed to present global, regional and national data on mortality and disability-adjusted life-year (DALY) for pancreatic cancer attributable to metabolic risk and to forecast mortality to 2030 using data from the Global Burden of Disease (GBD). METHODS: Data on mortality and DALYs due to pancreatic cancer attributable to metabolic risks were obtained from GBD 2019. Metabolic risks include high fasting plasma glucose (FPG) and high body mass index (BMI). Total numbers and age-standardized rates per 100,000 people for mortality and DALYs were reported by age, sex, region and country/territory from 1990 to 2019. The "Bayes age-period-cohort" method was used for projections of mortality to 2030. RESULTS: Globally, there was a 3.5-fold increase in the number of pancreatic cancer deaths attributable to metabolic risk, from 22,091 in 1990 to 77,215 in 2019. High-income North America and Central Europe had the highest age-standardized mortality rates (ASMRs) of pancreatic cancer attributable to high FPG and high BMI in 2019, respectively. From 1990 to 2019, the global ASMR of pancreatic cancer attributable to high FPG and high BMI increased. Countries with high healthcare access quality had much higher age-standardized DALY rates. In the next 10 years, the ASMR of pancreatic cancer attributable to high FPG and high BMI will continue to increase. CONCLUSION: Pancreatic cancer mortality and DALYs attributable to metabolic factors remain high, particularly in high-income regions or countries. Studies on the metabolic mechanism of pancreatic cancer and effective treatment strategies are needed.

Cross-country health inequalities of four common nutritional deficiencies among children, 1990 to 2019: data from the Global Burden of Disease Study 2019.

BACKGROUND: Nutritional deficiencies remain serious medical and public health issues worldwide, especially in children. This study aims to analyze cross-country inequality in four common nutritional deficiencies (protein-energy malnutrition, dietary iron deficiency, vitamin A deficiency and iodine deficiency) among children from 1990 to 2019 based on Global Burden of Disease (GBD) 2019 data. METHODS: Prevalence and disability-adjusted life years (DALYs) data as measures of four nutritional deficiency burdens in people aged 0 to 14 years were extracted from the GBD Results Tool. We analyzed temporal trends in prevalence by calculating the average annual percent change (AAPC) and quantified cross-country inequalities in disease burden using the slope index. RESULTS: Globally, the age-standardized prevalence rates of dietary iron deficiency, vitamin A deficiency and iodine deficiency decreased, with AAPCs of -0.14 (-0.15 to -0.12), -2.77 (-2.96 to -2.58), and -2.17 (-2.3 to -2.03) from 1999 to 2019, respectively. Significant reductions in socio-demographic index (SDI)-related inequality occurred in protein-energy malnutrition and vitamin A deficiency, while the health inequality for dietary iron deficiency and iodine deficiency remained basically unchanged. The age-standardized prevalence and DALY rates of the four nutritional deficiencies decreased as the SDI and healthcare access and quality index increased. CONCLUSIONS: The global burden of nutritional deficiency has decreased since 1990, but cross-country health inequalities still exist. More efficient public health measures are needed to reduce disease burdens, particularly in low-SDI countries/territories.

Research advances of MAL family members in tumorigenesis and tumor progression (Review).

The myelin and lymphocyte protein (MAL) family is a novel gene family first identified and characterized in 2002. This family is comprised of seven members, including MAL, MAL2, plasmolipin, MALL, myeloid differentiation­associated marker (MYADM), MYADML2 and CMTM8, which are located on different chromosomes. In addition to exhibiting extensive activity during transcytosis, the MAL family plays a vital role in the neurological, digestive, respiratory, genitourinary and other physiological systems. Furthermore, the intimate association between MAL and the pathogenesis, progression and metastasis of malignancies, attributable to several mechanisms such as DNA methylation has also been elucidated. In the present review, an overview of the structural and functional properties of the MAL family and the latest research findings regarding the relationship between several MAL members and various cancers is provided. Furthermore, the potential clinical and scientific significance of MAL is discussed and directions for future research are summarized.

Establishment and characterization of DPC-X4: a novel mixed-type ampullary cancer cell line.

Mixed-type ampullary cancer is a distinct subtype of ampullary cancer that manifests a merging of the biological characteristics of both intestinal and pancreaticobiliary subtypes. The absence of established cell lines specific to this subtype has resulted in a concomitant scarcity of research on its tumorigenic mechanisms and the development of novel therapeutic modalities. The present study achieved the successful establishment of a novel mixed-type ampullary cancer cell line, designated DPC-X4 through primary culture techniques. Subsequent analyses pertaining to phenotypic characteristics, molecular profiling, biomarker identification, and histological features validated the DPC-X4 cell line as a potent model for delineating the pathogenesis of mixed-type ampullary cancer and facilitating the development of new pharmacological agents. This newly established cell line was subjected to continuous cultivation for 1 year, with stable passaging for over 50 generations. Notably, the DPC-X4 cell line manifested typical morphological features associated with epithelial tumors. Furthermore, the population doubling time for the DPC-X4 cell line was determined at 70 h. Short tandem repeat (STR) analysis confirmed that the DPC-X4 cell line exhibited a high genetic concordance with the primary tumor from the patient. Karyotypic profiling indicated an abnormal sub-triploid karyotype, with representative karyotypes of 57, XXY inv (9), 14p + , 15p + , der (17), + mar. The DPC-X4 cell line demonstrated a high capacity for efficient organoid formation under suspension culture conditions. In addition, the subcutaneous inoculation of DPC-X4 cells into NXG mice led to the formation of xenografted tumors. The results of drug sensitivity testing indicated that DPC-X4 cells were sensitive to paclitaxel and resistant to oxaliplatin, 5-fluorouracil, and gemcitabine. Immunohistochemistry revealed positive expression of CK7, CK19, and CK20 in DPC-X4 cells, while CDX2 demonstrated negative expression. In addition, positive expression of E-cadherin and vimentin was identified in DPC-X4 cells, with a proliferation index indicated by Ki-67 at 70%. The findings of our study establish DPC-X4 as a novel mixed-type ampullary cancer cell line, which can serve as a potential experimental model for exploring the pathogenesis of ampullary cancer and the development of therapeutic drugs.

A risk signature based on endoplasmic reticulum stress-associated genes predicts prognosis and immunity in pancreatic cancer.

Introduction: The involvement of endoplasmic reticulum (ER) stress in cancer biology is increasingly recognized, yet its role in pancreatic cancer (PC) remains unclear. This study aims to elucidate the impact of ER stress on prognosis and biological characteristics in PC patients. Methods: A bioinformatic analysis was conducted using RNA-seq data and clinicopathological information from PC patients in the TCGA and ICGC databases. The ER stress-associated gene sets were extracted from MSigDB. ER stress-associated genes closely linked with overall survival (OS) of PC patients were identified via log-rank test and univariate Cox analysis, and further narrowed by LASSO method. A risk signature associated with ER stress was formulated using multivariate Cox regression and assessed through Kaplan-Meier curves, receiver operating characteristic (ROC) analyses, and Harrell's concordance index. External validation was performed with the ICGC cohort. The single-sample gene-set enrichment analysis (ssGSEA) algorithm appraised the immune cell infiltration landscape. Results: Worse OS in PC patients with high-risk signature score was observed. Multivariate analysis underscored our ER stress-associated signature as a valuable and independent predictor of prognosis. Importantly, these results based on TCGA were further validated in ICGC dataset. In addition, our risk signature was closely associated with homeostasis, protein secretion, and immune regulation in PC patients. In particular, PC microenvironment in the high-risk cluster exhibited a more immunosuppressive status. At last, we established a nomogram model by incorporating the risk signature and clinicopathological parameters, which behaves better in predicting prognosis of PC patients. Discussion: This comprehensive molecular analysis presents a new predictive model for the prognosis of PC patients, highlighting ER stress as a potential therapeutic target. Besides, the findings indicate that ER stress can have effect modulating PC immune responses.

Biological Roles and Pathogenic Mechanisms of LncRNA MIR4435-2HG in Cancer: A Comprehensive Review.

The long non-coding RNA MIR4435-2HG has been confirmed to play a crucial regulatory role in various types of tumors. As a novel type of non-coding RNA, MIR4435-2HG plays a key role in regulating the expression of tumor-related genes, interfering with cellular signaling pathways, and affecting tumor immune evasion. Its unique structure allows it to regulate the expression of various tumor-related genes through different pathways, participating in the regulation of tumor signaling pathways, such as regulating the expression of oncogenes and tumor suppressor genes, influencing the biological behaviors of proliferation, metastasis, and apoptosis in tumors. Numerous studies have found a high expression of MIR4435-2HG in various tumor tissues, closely related to the clinical pathological characteristics of tumors, such as staging, lymph node metastasis and prognosis. Some studies have discovered that MIR4435-2HG can regulate the sensitivity of tumor cells to chemotherapy drugs, affecting tumor cell drug resistance. This provides new insights into overcoming tumor drug resistance by regulating MIR4435-2HG. Therefore, studying its molecular mechanisms, expression regulation, and its relationship with the clinical features of tumors is of great significance for revealing the mechanisms of tumor occurrence and developing new therapeutic targets.

Microbiota in cancer: molecular mechanisms and therapeutic interventions.

The diverse bacterial populations within the symbiotic microbiota play a pivotal role in both health and disease. Microbiota modulates critical aspects of tumor biology including cell proliferation, invasion, and metastasis. This regulation occurs through mechanisms like enhancing genomic damage, hindering gene repair, activating aberrant cell signaling pathways, influencing tumor cell metabolism, promoting revascularization, and remodeling the tumor immune microenvironment. These microbiota-mediated effects significantly impact overall survival and the recurrence of tumors after surgery by affecting the efficacy of chemoradiotherapy. Moreover, leveraging the microbiota for the development of biovectors, probiotics, prebiotics, and synbiotics, in addition to utilizing antibiotics, dietary adjustments, defensins, oncolytic virotherapy, and fecal microbiota transplantation, offers promising alternatives for cancer treatment. Nonetheless, due to the extensive and diverse nature of the microbiota, along with tumor heterogeneity, the molecular mechanisms underlying the role of microbiota in cancer remain a subject of intense debate. In this context, we refocus on various cancers, delving into the molecular signaling pathways associated with the microbiota and its derivatives, the reshaping of the tumor microenvironmental matrix, and the impact on tolerance to tumor treatments such as chemotherapy and radiotherapy. This exploration aims to shed light on novel perspectives and potential applications in the field.

Interplay between the Human Microbiome and Biliary Tract Cancer: Implications for Pathogenesis and Therapy.

Biliary tract cancer, encompassing intrahepatic and extrahepatic cholangiocarcinoma as well as gallbladder carcinoma, stands as a prevalent malignancy characterized by escalating incidence rates and unfavorable prognoses. The onset of cholangiocarcinoma involves a multitude of risk factors and could potentially be influenced by microbial exposure. The human microbiome, encompassing the entirety of human microbial genetic information, assumes a pivotal role in regulating key aspects such as host digestion, absorption, immune responses, and metabolism. The widespread application of next-generation sequencing technology has notably propelled investigations into the intricate relationship between the microbiome and diseases. An accumulating body of evidence strongly suggests a profound interconnection between biliary tract cancer and the human microbiome. This article critically appraises the existing evidence pertaining to the microbiome milieu within patients afflicted by biliary tract cancer. Furthermore, it delves into potential mechanisms through which dysregulation of the human microbiome could contribute to the advancement of biliary tract cancer. Additionally, the article expounds on its role in the context of chemotherapy and immunotherapy for biliary tract cancer.

Research trends on immunotherapy for pancreatic cancer: A bibliometric analysis.

This study aims to summarize and visually analyze the current research status in pancreatic cancer immunotherapy during the past two decades by bibliometrics and explore the current research hotspots and future development directions. The literature related to pancreatic cancer immunotherapy from 2002 to 2021 was downloaded from the core database of the Web of Science. VOSviewer and CiteSpace software were used to visualize the included literature. A total of 2528 articles were included. In the past two decades, publications in the pancreatic cancer immunotherapy field have increased almost annually. As the country with the largest publications, the United States has various research institutions dedicated to pancreatic cancer immunotherapy. Jaffee EM and Zheng L from Johns Hopkins University and Vonderheide RH from the University of Pennsylvania have published the most articles in this field. The current research hotspots of pancreatic cancer immunotherapy include the tumor microenvironment, immune cells, immune checkpoint blockade, and combination therapy. The study of novel immunotherapies and combination therapy may become the primary focus of future research on pancreatic cancer immunotherapy. More prospective clinical studies with high evidence levels should be conducted.

Integrated transcriptomics, proteomics and metabolomics-based analysis uncover TAM2-associated glycolysis and pyruvate metabolic remodeling in pancreatic cancer.

Introduction: Tumor-associated macrophage 2 (TAM2) abundantly infiltrates pancreatic ductal adenocarcinoma (PAAD), and its interaction with malignant cells is involved in the regulation of tumor metabolism. In this study, we explored the metabolic heterogeneity involved in TAM2 by constructing TAM2-associated metabolic subtypes in PAAD. Materials and methods: PAAD samples were classified into molecular subtypes with different metabolic characteristics based on a multi-omics analysis strategy. 20 PAAD tissues and 10 normal pancreatic tissues were collected for proteomic and metabolomic analyses. RNA sequencing data from the TCGA-PAAD cohort were used for transcriptomic analyses. Immunohistochemistry was used to assess TAM2 infiltration in PAAD tissues. Results: The results of transcriptomics and immunohistochemistry showed that TAM2 infiltration levels were upregulated in PAAD and were associated with poor patient prognosis. The results of proteomics and metabolomics indicated that multiple metabolic processes were aberrantly regulated in PAAD and that this dysregulation was linked to the level of TAM2 infiltration. WGCNA confirmed pyruvate and glycolysis/gluconeogenesis as co-expressed metabolic pathways of TAM2 in PAAD. Based on transcriptomic data, we classified the PAAD samples into four TAM2-associated metabolic subtypes (quiescent, pyruvate, glycolysis/gluconeogenesis and mixed). Metabolic subtypes were each characterized in terms of clinical prognosis, tumor microenvironment, immune cell infiltration, chemotherapeutic drug sensitivity, and functional mechanisms. Conclusion: Our study confirmed that the metabolic remodeling of pyruvate and glycolysis/gluconeogenesis in PAAD was closely related to TAM2. Molecular subtypes based on TAM2-associated metabolic pathways provided new insights into prognosis prediction and therapy for PAAD patients.

Comprehensive Analysis Identifies PKP3 Overexpression in Pancreatic Cancer Related to Unfavorable Prognosis.

Plakophilin 3 (PKP3) affects cell signal transduction and cell adhesion and performs a crucial function in tumorigenesis. The current investigation evaluated the predictive significance and underlying processes of PKP3 within pancreatic cancer (PC) tissues. The assessment of differences in PKP3 expression was conducted through an analysis of RNA-seq data acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, clinical samples were collected to validate the findings. The predictive significance of PKP3 was investigated by analyzing survival data derived from TCGA and clinical specimens. PKP3's biological function was assessed via phenotypic experiments after the suppression of PKP3 expression within PC cells. Functional enrichment analysis, encompassing KEGG, GO, and GSEA, was employed to assess the underlying mechanism of PKP3. Immune infiltration analysis was conducted in the present investigation to determine the association between PKP3 and tumor-infiltrating immune cells (TICs). In PC tissues, PKP3 expression was abnormally upregulated and correlated with a negative prognosis in individuals with PC. PKP3 can promote the progression, migration, and invasive capacity of PC cells and is relevant to the regulation of the PI3K-Akt and MAPK signaling pathways. Immune infiltration analysis demonstrated that PKP3 impeded CD8+ T-cell infiltration and immune cytokine expression within the tumor microenvironment. The PKP3 protein was identified as a prospective independent predictive indicator and represents a viable approach for immunotherapy in the context of PC. PKP3 may impact prognosis by broadly inhibiting immune cell infiltration and promoting the activation of tumor-associated signaling pathways.

Time trend of pancreatic cancer mortality in the Western Pacific Region: age-period-cohort analysis from 1990 to 2019 and forecasting for 2044.

BACKGROUND: Pancreatic cancer poses a serious medical problem worldwide. Countries in the Western Pacific Region are facing public health challenges from cancer. This study assesses the time trends of pancreatic cancer mortality in the Western Pacific Region from 1990 to 2019 and predicts its trend to 2044. METHODS: Mortality data were obtained from the Global Health Data Exchange. We used an age-period-cohort model to estimate age, period and birth cohort effects on pancreatic cancer mortality from 1990 to 2019 by calculating net drift, local drift, age-specific rate, period rate ratio, and cohort rate ratio. We also predict pancreatic cancer mortality to 2044 in Western Pacific countries. RESULTS: Overall, there were 178,276 (95% uncertain interval: 157,771 to 198,636) pancreatic cancer deaths in the Western Pacific Region in 2019, accounting for 33.6% of all deaths due to pancreatic cancer worldwide. There were significant increases in pancreatic cancer disability-adjusted life years between 1990 and 2019 in the Western Pacific Region, mainly due to population growth and aging. Pancreatic cancer mortality increased with age. The period effect showed an increasing trend of mortality for both sexes over the study period. Compared to the reference period (2000 to 2004), the rate ratio was elevated in both males and females in the period of 2015 to 2019. There was an overall increasing rate ratio from early birth cohorts to recent cohorts. Deaths may continue to increase in the next 25 years in the ten countries, while most countries have seen their age-standardized rate forecasts fall. CONCLUSION: The mortality of pancreatic cancer is still high in the Western Pacific Region. Countries/territories should focus on pancreatic cancer prevention and early cancer screening in high-risk populations. Specific public health methods and policies aimed at reducing risk factors for pancreatic cancer are also needed.

Integration of Single-Cell RNA Sequencing and Bulk RNA Sequencing Reveals That TAM2-Driven Genes Affect Immunotherapeutic Response and Prognosis in Pancreatic Cancer.

Tumor-associated macrophages M2 (TAM2), which are highly prevalent infiltrating immune cells in the stroma of pancreatic cancer (PC), have been found to induce an immunosuppressive tumor microenvironment, thus enhancing tumor initiation and progression. However, the immune therapy response and prognostic significance of regulatory genes associated with TAM2 in PC are currently unknown. Based on TCGA transcriptomic data and single-cell sequencing data from the GEO database, we identified TAM2-driven genes using the WGCNA algorithm. Molecular subtypes based on TAM2-driven genes were clustered using the ConsensusClusterPlus algorithm. The study constructed a prognostic model based on TAM2-driven genes through Lasso-COX regression analysis. A total of 178 samples obtained by accessing TCGA were accurately categorized into two molecular subtypes, including the high-TAM2 infiltration (HMI) cluster and the low-TAM2 infiltration (LMI) cluster. The HMI cluster exhibits a poor prognosis, a malignant tumor phenotype, immune-suppressive immune cell infiltration, resistance to immunotherapy, and a high number of genetic mutations, while the LMI cluster is the opposite. The prognostic model composed of six hub genes from TAM2-driven genes exhibits a high degree of accuracy in predicting the prognosis of patients with PC and serves as an independent risk factor. The induction of TAM2 was employed as a means of verifying these six gene expressions, revealing the significant up-regulation of BCAT1, BST2, and MERTK in TAM2 cells. In summary, the immunophenotype and prognostic model based on TAM2-driven genes offers a foundation for the clinical management of PC. The core TAM2-driven genes, including BCAT1, BST2, and MERTK, are involved in regulating tumor progression and TAM2 polarization, which are potential targets for PC therapy.

Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial.

BACKGROUND: Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. METHODS: This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. RESULTS: The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t = 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26-0.71, P <0.001) and 0.76 (95% CI: 0.57-0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05-0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39-0.95, P = 0.028) in the multivariable models. CONCLUSION: Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery. TRAIL REGISTRATION: ClinicalTrials.gov, No. NCT03075280.

Pancreatic stellate cells in pancreatic cancer: as potential targets for future therapy.

Pancreatic cancer is a strongly malignant gastrointestinal carcinoma characterized by late detection, high mortality rates, poor patient prognosis and lack of effective treatments. Consequently, there is an urgent need to identify novel therapeutic strategies for this disease. Pancreatic stellate cells, which constitute a significant component of the mesenchymal cellular layer within the pancreatic tumor microenvironment, play a pivotal role in modulating this environment through their interactions with pancreatic cancer cells. This paper reviews the mechanisms by which pancreatic stellate cells inhibit antitumor immune responses and promote cancer progression. We also discuss preclinical studies focusing on these cells, with the goal of providing some theoretical references for the development of new therapeutic approaches for pancreatic cancer.