This study aims to compare the intraoperative and short-term postoperative efficacies between robotic-assisted and conventional laparoscopic approaches for spleen-sparing left pancreatectomy. Both minimally invasive modalities were executed by adopting the Splenic Artery and Vein Anatomical Plane First (SAPP) surgical philosophy. A retrospective assessment was conducted on patients who received minimally invasive distal pancreatectomies with Kimura-style splenic preservation from January 2019 to September 2024. To mitigate potential selection bias and equilibrate baseline variables across the cohorts, a 1:1 propensity score matching (PSM) protocol was implemented. Subsequent comparative analyses focused on both intraoperative metrics and postoperative clinical outcomes within the matched pairs. Of the 113 total participants, those undergoing robotic spleen-preserving distal pancreatectomy (RSPDP) experienced notably less intraoperative bleeding than those in the laparoscopic spleen-preserving distal pancreatectomy (LSPDP) group (P = 0.039). This trend remained robust after PSM, which yielded 54 patients in 27 matched pairs; the RSPDP group maintained a significant advantage in minimizing blood loss (49.07 ± 34.64 mL vs. 78.15 ± 57.31 mL, P = 0.028). Regarding other perioperative metrics—specifically operative time, fistula occurrence, overall morbidity, and length of stay or readmission—the two approaches yielded comparable results with no significant variations observed. Both robotic and laparoscopic platforms demonstrate comparable and safe perioperative outcomes for spleen-preserving distal pancreatectomy under the SAPP framework. While the robotic approach offers a modest, statistically significant advantage in mitigating intraoperative blood loss during complex vascular skeletonization, its macroscopic clinical relevance requires further evaluation.

Introduction Metastatic pancreatic neuroendocrine tumors (pNETs) carry a poor prognosis. Currently, no validated model exists to accurately predict survival in this population, highlighting the need for effective prognostic tools. Materials and methods In this study, we developed and validated a machine learning-based survival prediction model using data from the Surveillance, Epidemiology, and End Results (SEER) database. The model incorporated ten key prognostic factors, including AJCC TNM stage (T, N, M), tumor grade, primary surgery, non-primary site surgery, chemotherapy, primary site, age, and sex. The eXtreme Gradient Boosting (XGBoost) algorithm was applied to construct the model. Results A total of 1430 patients were included in the study. The XGBoost model showed strong predictive performance, with area under the receiver operating characteristic curve (AUROC) values of 0.781, 0.747, and 0.741 for 1-, 3-, and 5-year survival, respectively. The model was implemented in a web-based application that delivers real-time, individualized survival estimates to support clinical decision-making and personalized treatment planning. Conclusion By capturing complex interactions among prognostic variables, the model provides accurate survival predictions and supports patient-centered care. It addresses a critical gap in prognostic tools for metastatic pNETs.

Non-coding RNAs (ncRNAs) are crucial molecules that do not encode proteins but play roles in regulating various biological processes. Recent research highlights that ncRNAs not only control gene expression within cells but also facilitate intercellular communication via exosomes and other carriers. This function is vital in the tumor microenvironment (TME). Our review covers the structure and functions of different ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). We examine how these ncRNAs influence tumor initiation and progression. Additionally, we explore their role in promoting tumor growth or immune evasion by modulating the TME. The potential of using these ncRNAs as therapeutic targets or biomarkers for clinical use is also discussed. As our understanding of ncRNAs grows, the development of new therapies based on ncRNAs is anticipated to offer improved treatment options for cancer patients.

Pancreatic cancer is highly aggressive and sensitive to acidic microenvironments, which promote cancer cell survival and invasion. Long non-coding RNAs (lncRNAs) play crucial roles in cancer biology, helping cells adapt to microenvironmental changes, but their functions in the acidic microenvironment of pancreatic cancer are understudied. This study investigated the role of lncRNA LOC100507424 in pancreatic cancer, previously linked to glioma stem cells. Clinical specimens and cell line models cultured under acidic conditions showed that LOC100507424 was upregulated in pancreatic cancer tissues and further increased in acidic environments. Functional assays demonstrated that knockdown of LOC100507424 inhibited cell proliferation, invasion and metastasis. Mechanistically, LOC100507424 transcriptionally regulated FOXM1 expression through its interaction with E2F1. In vivo studies confirmed that LOC100507424 promoted tumor growth in nude mice. These findings highlight the significance of lncRNAs in the acidic microenvironment of pancreatic cancer and suggest potential therapeutic targets.

Background: Non-cancer-specific death (NCSD) is an important factor that needs to be consid-ered in patients with malignancy, as it can affect their long-term prognosis. In particular, the effect of age on patients with hepatocellular carcinoma (HCC) after hepatectomy requires clar-ification. This study aims to examine the impact of age on patients with HCC after hepatectomy and to identify independent risk factors of survival. Methods: Patients with HCC that fell within the Milan Criteria and had undergone curative hepatec-tomy were included in this study. The patients were divided into two groups: young patients (age <70) and elderly patients (age >70). Perioperative complications, cancer-specific death (CSD), recurrence, and NCSD were all recorded and analyzed. Multivariate analyses were performed to identify independent risk factors of survival using Fine and Gray's competing-risk regression model. Results: Among 1,354 analytic patients, 1,068 (78.7%) were stratified into the young group and 286 (21.3%) into the elderly group. The elderly group had a higher 5-year cumulative incidence of NCSD (12.6% vs. 3.7% for the young group, P < 0.001), but lower 5-year cumulative incidences of recurrence (20.3% vs. 21.1% for the young group, P = 0.041) and CSD (14.3% vs. 15.5% for the young group, P = 0.066). Multivariate competing-risk regression analyses revealed that age was independently associated with NCSD (subdistribution hazard ratio (SHR) 3.003, 95%CI: 2.082-4.330, P < 0.001), but not with recurrence (SHR 0.837, 95%CI: 0.659-1.060, P = 0.120) or CSD (SHR 0.736, 95%CI: 0.537-1.020, P = 0.158). Conclusion: For patients with early-stage HCC after hepatectomy, older age was independently associated with NCSD, but not recurrence and CSD. (c) 2023 Elsevier Masson SAS. All rights reserved.

PDF file - 1881K, Figure S4. LV-shAMPKα1 suppresses tumourigenicity in nude mouse xenograft model.

Background Previous studies suggested that tumor size was an independent risk factor of prognosis for hepatocellular carcinoma (HCC). However, the general prognostic analysis did not consider the interaction between variables. The purpose of this study was to investigate whether the effect of tumor size on the prognosis of isolated HCC without vascular invasion varies according to covariates. Methods Patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database to investigate whether there was an interaction between age and tumor size on the prognosis. Then the trend test and the value of per 1 SD of tumor size were calculated. In addition, the data of Zhejiang Provincial People's Hospital meeting the requirements were selected to verify the obtained conclusions. Results Multivariable Cox regression analysis of the database cohort showed that age, gender, tumor size, pathological grade and marital status were independent risk factors for prognosis. Interaction test showed that there was an interaction between age and tumor size (P for interaction < 0.05). Stratified analysis by age showed that tumor size was an independent risk factor for prognosis when age ≤65 years old (HR:1.010,95%CI1.007–1.013 P < 0.001), while tumor size was not an independent risk factor for prognosis when age >65 years old. This result was confirmed by trend analysis (P for trend < 0.001), and the prognostic risk increased by 42.1% for each standard deviation increase of tumor size among patients age ≤65 years. Consistent conclusion was obtained by multivariable cox regression analysis and interaction test on the verification cohort. In the validation cohort, for each standard deviation increase of tumor size in patients ≤65 years old, the risk of prognosis increased by 52.4%. Conclusion Tumor size is not an independent risk factor for the prognosis of isolated HCC without vascular invasion when patient's age >65 years. Therefore, when analyzing the relationship between tumor size and prognosis, stratified analysis should be performed according to age.

ObjectiveEarly detection of a tumour remains an unmet medical need, and approaches with high sensitivity and specificity are urgently required. Mass cytometry time-of-flight (CyTOF) is a powerful technique to profile immune cells and could be applied to tumour detection. We attempted to establish diagnostic models for hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC).DesignWe performed CyTOF analysis for 2348 participants from 15 centres, including 1131 participants with hepatic diseases, 584 participants with pancreatic diseases and 633 healthy volunteers. Diagnostic models were constructed through random forest algorithm and validated in subgroups.ResultsWe determined the disturbance of systemic immunity caused by HCC and PDAC, and calculated a peripheral blood immune score (PBIScore) based on the constructed model. The PBIScore exhibited good performance in detecting HCC and PDAC, with both sensitivity and specificity being around 80% in the validation cohorts. We further established an integrated PBIScore (iPBIScore) by combining PBIScore and alpha-fetoprotein or carbohydrate antigen 19-9. The iPBIScore for HCC had an area under the curve (AUC) of 0.99, 0.97 and 0.96 in training, internal validation and external validation cohorts, respectively. Similarly, the iPBIScore for PDAC showed an AUC of 0.99, 0.98 and 0.97 in the training, internal validation and external validation cohorts, respectively. In early-stage and tumour-marker-negative patients, our iPBIScore-based models also showed an AUC of 0.95–0.96 and 0.81–0.92, respectively.ConclusionOur study proved that the alterations of peripheral immune cell subsets could assist tumour detection, and provide a ready-to-use detection model for HCC and PDAC.

Background Angiogenesis and tissue repair in chronic non-healing diabetic wounds remain critical clinical problems. Engineered MSC-derived exosomes have significant potential for the promotion of wound healing. Here, we discuss the effects and mechanisms of eNOS-rich umbilical cord MSC exosomes (UCMSC-exo/eNOS) modified by genetic engineering and optogenetic techniques on diabetic chronic wound repair. Methods Umbilical cord mesenchymal stem cells were engineered to express two recombinant proteins. Large amounts of eNOS were loaded into UCMSC-exo using the EXPLOR system under blue light irradiation. The effects of UCMSC-exo/eNOS on the biological functions of fibroblasts and vascular endothelial cells in vitro were evaluated. Full-thickness skin wounds were constructed on the backs of diabetic mice to assess the role of UCMSC-exo/eNOS in vascular neogenesis and the immune microenvironment, and to explore the related molecular mechanisms. Results eNOS was substantially enriched in UCMSCs-exo by endogenous cellular activities under blue light irradiation. UCMSC-exo/eNOS significantly improved the biological functions of cells after high-glucose treatment and reduced the expression of inflammatory factors and apoptosis induced by oxidative stress. In vivo, UCMSC-exo/eNOS significantly improved the rate of wound closure and enhanced vascular neogenesis and matrix remodeling in diabetic mice. UCMSC-exo/eNOS also improved the inflammatory profile at the wound site and modulated the associated immune microenvironment, thus significantly promoting tissue repair. Conclusion This study provides a novel therapeutic strategy based on engineered stem cell-derived exosomes for the promotion of angiogenesis and tissue repair in chronic diabetic wounds. Graphic Abstract

目的 探究胰腺神经内分泌肿瘤(pNETs)患者行腹腔镜手术后住院时间延长的危险因素.方法 回顾性分析2015年1月至2022年8月在浙江省人民医院行腹腔镜手术治疗的91例pNETs患者的临床资料.以术后住院时间是否超过中位住院时间12 d将患者分为住院时间正常组(NLOS组,≤12 d,n=50)和住院时间延长组(PLOS组,>12 d,n=41).通过单因素和多因素Logistic回归分析患者术后住院时间延长的危险因素,用AUC和Brier分数评价区分度和校准度.结果 单因素及多因素分析显示,手术时间>210 min(OR=8.850,95％CI 2.699～29.013,P<0.001)和腹腔镜手术方式[腹腔镜胰十二指肠切除术(LPD):OR=5.753,95％CI 1.062～31.155,P=0.042;腹腔镜胰腺体尾切除术(LDP:OR=8.547,95％CI 1.908～38.291,P=0.005]是患者住院时间延长的独立危险因素.此时相应的AUC为0.785,Brier分数为0.182.结论 手术时间和手术方式是预测pNETs患者腹腔镜术后住院时间是否延长的主要危险因素.

PDF - 3658KB, Supplementary Figure S3. Downregulation of MAP4K4 reverses the malignant behavior of pancreatic cancer cell lines. (A) The MAP4K4 expression was downregulated after treated with its siRNA determined by SYBR Green qRT-PCR (left) and western blot (right). (B) Knockdown of MAP4K4 suppressed the proliferation of PANC-1 and MiaPaCa-2 cells. (C) Downregulation of MAP4K4 weakened the ability of cell clonogenicity. (D) The cell invasion ability was measured at 48 h after cells seeded in chambers. Silencing of MAP4K4 decreased the ability of cell invasion. (E) Cell cycle was examined by flow cytometry. Compared to NC groups, cell cycle in siRNA-MAP4K4 groups was blocked at G1 phase. (F) The percentage of apoptotic cells increased through downregulation of MAP4K4 in pancreatic cancer cell lines. (G) Silencing of MAP4K4 increased chemosensitivity to 5-Fu and Gemcitabine based on IC50 data. (H) Western blot assay illustrated that after treated with MAP4K4 siRNA, MMP-2, cyclinD1 and Bcl-2 were downregulated while Bax was upregulated. But the changes of MMP-9 were not so significant. *P<0.05, **P<0.01.

OBJECTIVE: MED subunits have been reported to be associated with various types of tumors, however, the potential role of MED7 in hepatocellular carcinoma (HCC) was still unclear. The aim of the study was to explore the role of MED7 in HCC. METHODS: In this study, MED7 mRNA expression levels between HCC and adjacent normal tissues were first analyzed by several public datasets. Then we utilized a tissue microarray (TMA) to investigate the clinical role of MED7 in HCC by immunohistochemistry (IHC). Meanwhile, the potential mechanisms of MED7 based on gene-gene correlation analyses were also explored. RESULTS: High mRNA level of MED7 correlated with advanced stage and worse grade of differentiation. IHC results showed that MED7 protein level was upregulated in HCC and associated with Edmondson grade and Microvascular invasion in 330 cases of HCC. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed that MED7 co-expressed genes participate primarily in ribonucleoprotein complex biogenesis, protein targeting, mRNA processing and nucleoside triphosphate metabolic process et cetera. Further analysis also revealed that MED7 mRNA level has significant correlation with immune cells infiltration levels. CONCLUSION: MED7 was upregulated in HCC and correlated with progression of HCC. Meanwhile, MED7 may promote HCC through participating in multiple gene networks to influence tumorigenesis as well as immune response in HCC microenvironment.

PDF - 61KB, Western Blot primary antibody.

The transitory placenta develops during pregnancy and mediates the blood flow between the mother and the developing baby. Placental dysfunction, including but not limited to placenta accreta spectrum, fetal growth restriction, preeclampsia and gestational trophoblastic disease, arises from abnormal placental development and can result in significant adverse maternal and fetal health outcomes. Unfortunately, there is a lack of treatment alternatives for these disorders. Nanocarriers offer versatility, including extended circulation, organ-specific targeting and intracellular transport, finely tuning therapeutic placental interactions. This thorough review explores nanotechnological strategies for addressing placental disorders, encompassing dysfunction insights, potential drug-delivery targets and recent strides in placenta-targeted nanoparticle (NP) therapies, instilling hope for effective placental malfunction treatment.

Objective:To evaluate the safety and clinical efficacy of transcatheter arterial chemoembolization (TACE) combined with portal vein embolization (PVE) and percutaneous microwave ablation liver partition with PVE for planned hepatectomy in patients with hepatocellular carcinoma (HCC) with insu-fficient remnant liver volume.Methods:The clinical data of 51 patients with initially unresectable HCC due to insufficient remnant liver volume admitted to Zhejiang Provincial Tongde Hospital and Zhejiang Provincial People’s Hospital from January 2014 to December 2021 were retrospectively analyzed, including 37 males and 14 females, aged (56.7±11.2) years old. Patients were divided into two groups according to the treatment prior to hepatectomy: percutaneous microwave ablation liver partition combined with PVE (AP group, n=12) and TACE with PVE (TP group, n=39). Patients who successfully underwent planned hepatectomy in the above two groups were marked as resectable AP group ( n=10) and the resectable TP group ( n=29), respectively. Clinical data including the waiting time for surgery and the incidence of complications were analyzed. Patients were followed up by telephone or outpatient review. Kaplan-Meier and log-rank analysis were used for survival comparison. Results:The FLR growth rate was higher in AP group [76.5% (65.3%, 81.6%)] than that in TP group [31.4% (28.2%, 41.9%), P<0.01]. The waiting time for planned hepatectomy in the resectable AP group was 12.0 (11.3, 14.5) d, shorter than that in the resec-table TP group [21.0 (15.0, 29.0) d, P<0.05]. The incidence of postoperative complications was higher in the resectable AP group than that in the resectable TP group [80.0% (8/10) vs. 27.6% (8/29), P<0.05]. There was one perioperative death in the resectable AP group. The survival rate after PVE was lower in AP group than that in TP group, and the survival rate after hepatectomy was also lower in the resectable AP group than that in the resectable TP group (all P<0.05). Conclusion:For HCC patients with insufficient FLR, TACE combined with PVE is a safe and effective method for enlargement of liver remnant, whereas percutaneous microwave ablation liver partition with PVE showed a poor prognosis, despite the higher rate of FLR enlargement and shortened the waiting time for planned hepatectomy.

Duodenum-preserving pancreatic head resection (DPPHR) is very complicated due to its difficulty to find the lower common bile duct (CBD), and to preserve the blood supply of the duodenum and CBD. Recently, indocyanine green (ICG) has been widely applied for navigation during biliary system and liver surgery. However, the application of ICG-guided laparoscopic DPPHR has not been established. Herein, we report an intraoperative angiography technique using ICG fluorescence imaging to visualise blood flow, tissue perfusion, CBD navigation and bile leakage assessment.

Introduction Many nanocarriers have been developed to react physicochemically to exterior stimuli like ultrasonic, light, heat, and magnetic fields, along with various internal stimuli including pH, hypoxia, enzyme, and redox potential. Nanocarriers are capable to respond various stimuli within the cancer cells to enable on-demand drug delivery, activation of bioactive compounds, controlled drug release, and targeting ligands, as well as size, charge, and conformation conversion, enabling sensing and signaling, overcoming multidrug resistance, accurate diagnosis, and precision therapy. Areas covered Carbohydrates are ubiquitous biomolecules with a high proclivity for supramolecular network formation. Numerous carbohydrate-based nanomaterials have been used in biological solicitations and stimuli-based responses. Particular emphasis has been placed on the utilization of carbohydrate-based NPs and nanogels in various fields including imaging, drug administration, and tissue engineering. Because the assembly process is irreversible, carbohydrate-based systems are excellent ingredients for the development of stimulus-responsive nanocarriers for cancer-targeted chemotherapy. This review aims to summarise current research on carbohydrate-based nanomaterials, with an emphasis on stimuli-sensitive nanocarriers for cancer-targeted chemotherapy. Expert opinion Carbohydrates-based stimulus-responsive nanomaterials have been proved highly efficient for targeted delivery of anticancer drugs, thus leading to effective chemotherapy with minimum off-target effects.

Inside Front Cover In article number 2200997, Chen, Fan, Liu, and co-workers summarize the catalytic mechanism of nanozymes, the biocompatibility improving strategies of nanozymes, and the application in regeneration medicine including wound healing, nerve defect repair, bone regeneration, and cardiovascular disease treatment. This review highlights the research progress in this field, considering the rapid development of nanozymes applied in regeneration medicine recently.

In most cancers, forkhead box N3 (FOXN3) acts as a transcriptional inhibitor to suppress tumor proliferation, but in pancreatic cancer, the opposite effect is observed. To confirm and investigate this phenomenon, FOXN3 expression in various carcinomas was determined using GEPIA2 and was found to be highly expressed in pancreatic cancer. Kaplan-Meier plotter was then used for survival analysis, revealing that high FOXN3 expression in pancreatic cancer might be associated with a poor prognosis. Similarly, clinical samples collected for immunohistochemical staining and survival analysis showed consistent results. The RNA-seq data of pancreatic cancer patients from the TCGA were then downloaded, and the differential expression gene set was obtained using R for gene set enrichment analysis (GSEA). The intersection of the above gene sets and FOXN3-related genes was defined as related differentially expressed gene sets (DEGs), and enrichment analysis was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, we analyzed the relationship between FOXN3 and immune infiltration in pancreatic cancer. Collectively, our findings reveal that FOXN3 is involved in the occurrence and progression of pancreatic cancer and may be useful as a prognostic tool in pancreatic cancer immunotherapy.

Nanozymes refer to nanomaterials that catalyze enzyme substrates into products under relevant physiological conditions following enzyme kinetics. Compared to natural enzymes, nanozymes possess the characteristics of higher stability, easier preparation, and lower cost. Importantly, nanozymes possess the magnetic, fluorescent, and electrical properties of nanomaterials, making them promising replacements for natural enzymes in industrial, biological, and medical fields. On account of the rapid development of nanozymes recently, their application potentials in regeneration medicine are gradually being explored. To highlight the achievements in the regeneration medicine field, this review summarizes the catalytic mechanism of four types of representative nanozymes. Then, the strategies to improve the biocompatibility of nanozymes are discussed. Importantly, this review covers the recent advances in nanozymes in tissue regeneration medicine including wound healing, nerve defect repair, bone regeneration, and cardiovascular disease treatment. In addition, challenges and prospects of nanozyme researches in regeneration medicine are summarized.