Background: Curative-intent surgery for hilar cholangiocarcinoma (HCCA) comprises bile duct resection (BDR) alone, BDR combined with limited-volume hepatectomy (LVH) or extensive hepatectomy (EH). Consensus need to be reached regarding the optimal treatment modalities. We aimed to comparatively evaluate the postoperative outcomes of limited resection versus EH. Materials and Methods: This review adhered to the PRISMA and AMSTAR guidelines. A systematic literature search was performed in PubMed and Web of science for studies published up to June 18, 2025. All study designs (except case reports, comments, editorials, and reviews), that investigated postoperative outcomes in adults undergoing curative surgery for HCCA were considered, without language restrictions. Results: A total of 92 of the 4353 articles were analyzed. Compared with limited resection, EH was associated with higher rates of overall morbidity (56.5% vs. 39.3%; OR 1.89, 95% CI 1.62–2.19; P < 0.00001), major morbidity (37.3% vs. 16.4%; OR 2.35, 95% CI 1.78–3.10; P < 0.00001), and mortality (8.8% vs. 5.0%; OR 2.09, 95% CI 1.58–2.77; P < 0.00001). However, EH was also associated with lower rate of positive surgical margin (22.3% vs. 40.3%; OR 0.44, 95% CI 0.38–0.50; P < 0.00001), improved overall survival (HR 0.69, 95% CI 0.56–0.86; P = 0.0008), and a higher 5-year survival rate (30.5% vs. 20.7%; OR 1.48, 95% CI 1.24–1.76; P < 0.0001). Subgroup analysis comparing EH and LVH indicated that LVH reduced overall morbidity (37.3% vs. 59.1%; OR 0.69, 95% CI 0.52–0.91; P = 0.008) and major morbidity (25% vs. 36.7%; OR 0.67, 95% CI 0.45–1.00; P = 0.05). Although, the positive surgical margin rate was higher in the LVH group (21.9% vs. 19.7%; OR 1.38, 95% CI 1.03–1.85; P = 0.03), there were no significant differences in overall survival (HR 0.78, 95% CI 0.49–1.23; P = 0.29) or 5-year survival rate (29.5% vs. 31.5%; OR 0.88, 95% CI 0.62–1.24; P = 0.45), compared with EH. Conclusion: BDR alone is an insufficient curative procedure for HCCA, and should be applied cautiously. LVH represents a viable alternative to EH, particularly in patients with inadequate future liver remnant.

Background:Locally advanced pancreatic cancer (LAPC) is mostly unresectable at initial diagnosis. Conversion therapy has become core treatment to downstage tumors for radical resection, yet consensus on optimal first-line regimen remains lacking. This real-world study compared three mainstream conversion regimens and identified independent survival predictors to guide individualized treatment. Methods:A single-center retrospective cohort of 172 unresectable LAPC patients receiving gemcitabine plus nab-paclitaxel (AG), modified FOLFIRINOX (mFOLFIRINOX), or AG sequential chemoradiotherapy (CRT) from 2019 to 2023 was enrolled. Tumor conversion, surgical, survival and safety outcomes were analyzed. Cox regression was adopted to screen independent prognostic factors, with P<0.05 defined as statistical significance. Results:The overall conversion rate reached 38.4%. mFOLFIRINOX yielded the highest conversion rate (52.8%) versus AG (32.6%) and AG + CRT (33.3%). Among 66 converted patients, 87.9% achieved R0 resection, with 34.8% major pathological response (MPR). Median overall survival (OS) of converted patients reached 32.5 months, far superior to non-converted cases (12.3 months). Multivariate analysis confirmed preoperative carbohydrate antigen 19-9 (CA19-9) normalization and prognostic nutritional index (PNI) ≥41.7 as two independent favorable prognostic markers. Grade 3-4 adverse events were most frequent in the mFOLFIRINOX group (56.6%). Conclusions:For physically fit unresectable LAPC patients, mFOLFIRINOX provides superior conversion efficacy despite higher toxicity. Normalized CA19-9 and well-maintained nutritional status are reliable prognostic biomarkers. This real-world evidence supports mFOLFIRINOX as preferred first-line conversion regimen and routine monitoring of CA19-9 and nutrition during therapy.

Background:Circular RNAs (circRNAs) play a pivotal role in the development and advancement of various cancer types. However, the involvement of circ-PAN3 in hepatocellular carcinoma (HCC) is not well understood. To shed light on this, we conducted a comprehensive study through biochemistry, cell biology, molecular biology, and bioinformatics techniques to investigate the role of circ-PAN3 and its associated pathway in the progression of HCC. Methods:Cell Counting Kit-8 (CCK-8) assay and colony formation assay were utilized to evaluate cell proliferation; Quantitative real-time PCR (RT-qPCR) and Western blot were adopted for assessing mRNA and protein expression; Annexin V/propidium iodide (PI) staining was applied to detect cellular apoptosis; CircInteractome and Targetscan databases were searched to predict potential targets of circRNA and miRNA; Luciferase reporter assay and RNA pull-down assay were performed to examine the interaction of RNA molecules. Conclusions:Our findings revealed a significant increase in circ-PAN3 expression in HCC clinical specimens, which correlated with a poor survival rate in HCC patients. Knockdown of circ-PAN3 resulted in impaired cell proliferation, reduced cell survival, and inhibited tumorigenesis of HCC in vivo. Further analysis demonstrated that circ-PAN3 could serve as a sponge for miR-153, leading to a decrease in its expression level. This in turn upregulated cyclin D1 and ultimately promoted the proliferation of HCC cells. Additionally, overexpression of cyclin D1 mitigated the inhibitory effect on HCC proliferation induced by circ-PAN3 knockdown. Our study highlights the presence of a novel circ-PAN3/miR-153/cyclin D1 regulatory axis that plays a crucial role in the progression of HCC.

BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in the liver in individuals who do not consume alcohol. Several risk factors influencing the onset of NAFLD after laparoscopic pancreaticoduodenectomy (LPD) have been identified. This study investigated the risk factors associated with the development of fatty liver after laparoscopic duodenum-preserving pancreatic total head resection (LDPPHRt) and LPD. AIM:To compare the effects of LDPPHRt and LPD on the development of postoperative NAFLD. METHODS:This retrospective cohort study included 59 patients who were histologically diagnosed with benign or low-grade malignant pancreatic tumors and who underwent laparoscopic pancreatic surgery (LDPPHRt or LPD) between May 2020 and April 2023. Patient data on perioperative and postoperative variables were analyzed and compared. Multivariate logistic regression was used to identify pre-, peri-, and postoperative risk factors for NAFLD, with statistical significance set at P < 0.05. RESULTS:Of the 59 patients included in the study, 17 (28.8%) developed NAFLD within 6-12 months post-surgery. The incidence of NAFLD was significantly higher in the LPD group compared to the LDPPHRt group (40.0% vs 12.5%, P = 0.022). Multivariable analysis identified the LDPPHRt surgical approach (compared to LPD) as an independent protective factor against the development of postoperative NAFLD, with an odds ratio of 0.208 (95% confidence interval: 0.046-0.931; P = 0.040). CONCLUSION:Our findings indicate that LDPPHRt is more effective than LPD in reducing the incidence of postoperative NAFLD, which may inform surgical decision-making and optimize patient outcomes after laparoscopic pancreatic surgery.

Keloid is a cutaneous fibrotic disorder distinguished by uncontrolled dermal fibroblast proliferation and accumulation of collagen. N6-methyladenosine (M6A) modification is the most prevalent epitranscriptomic modification of eukaryotic mRNAs. M6A modification participates in a variety of biological processes of cells by influencing the stability, translation efficiency, splicing, and transport of mRNAs. Recently, m6A modification in keloids has garnered interest but is not fully understood. In this study, we discovered that keloids were in hyper-m6A-modified status, and HNRNPC was overexpressed in keloid tissues and keloid fibroblasts. The knockdown of HNRNPC inhibited the migration and proliferation of keloid fibroblasts. Through RNA immunoprecipitation PCR and luciferase experiments, WDR77 was identified as an m6A-dependent direct downstream target of HNRNPC. Furthermore, HNRNPC promoted the expression of WDR77 by increasing WDR77 stability, elevating the expression of TGF-β and SMAD3. In keloid xenograft nude mice, HNRNPC small interfering RNAs significantly limited keloid development with reduced WDR77 and TGF-β expression. Thus, our study revealed that HNRNPC regulated the pathological functions of keloid fibroblasts through the m6A methylation of WDR77 mRNA and that the inhibition of HNRNPC limited keloid progression in vivo. Our results decipher an m6A-related mechanism and potential therapeutic strategy for combating keloids.

The development of gemcitabine (GEM) resistance severely limits the treatment efficacy in pancreatic cancer (PC) and increasing evidence highlights the vital roles of circular RNAs (circRNAs) in the tumorigenesis, progression and drug resistance of PC. However, the circRNAs underlying GEM resistance development of PC remains to be clarified. The current research aims to unveil the roles of circ_0036627 in dictating the aggressiveness and GEM sensitivity in PC. We reported the increased expression of circ_0036627 in PC tissues and PC cell lines. Elevated circ_0036627 expression level was correlated with advanced tumour grade and poor overall survival in PC patients. Functional assays and in vivo experiments demonstrated that circ_0036627 overexpression was required for the proliferation, migration invasion and GEM resistance in PC cells. circ_0036627 knockdown suppressed tumour development in vivo. The molecular analysis further showed that circ_0036627 increased S100A16 expression by sponging microRNA-145 (miR-145), a tumour-suppressive miRNA that could significantly attenuate PC cell proliferation, migration, invasion and GEM resistance. Furthermore, our findings suggested that S100A16 acted as an oncogenic factor to promote aggressiveness and GEM resistance in PC cells. In conclusion, the current findings provide new mechanistic insights into PC aggressiveness and GEM resistance, suggesting the critical role of circ_0036627/miR-145/S100A16 axis in PC progression and drug resistance development and offering novel therapeutic targets for PC therapy.

Pancreatic cancer is the seventh leading cause of cancer death worldwide, which is demonstrated with remarkable resistance to radiotherapy and chemotherapy. The identification of prognosis signature and novel prognostic markers will facilitate patient stratification and an individualized precision therapy strategy. In this study, TCGA-PAAD was used to screen prognostic E3 ubiquitin ligases and establish prognostic signatures, and GEO database was used to verify the accuracy of prognostic signatures. Functional analysis, in vitro experiments and clinical cohort studies were used to analyze the function and prognostic efficacy of the target gene. An E3 ligase-based signature of 9 genes and the nomogram were developed, and the signature was proved to accurately predict the prognosis of patients with pancreatic cancer. WDR37 might be the most prognostic E3 ubiquitin ligase in pancreatic cancer, and the clinical cohort analyses suggested a tumor‐suppressive role. The results of functional analysis and in vitro experiments indicated that WDR37 may promote the degradation of TCP1 complex to inhibit tumor and improve immune cell infiltration. The E3 ligase-based signature accurately predicted the prognosis of patients with pancreatic cancer, so it can be used as a decision-making tool to guide the treatment of patients with pancreatic cancer. At the same time, WDR37, the main gene in E3PMP signature, can be used as the most prognostic E3 ubiquitin ligase in the treatment of pancreatic cancer.

BACKGROUND:The authors aimed to compare the differences in quality of life (QOL) and overall survival (OS) between duodenum-preserving pancreatic head resection (DPPHR) and pancreatoduodenectomy (PD) during long-term follow-up. DPPHR and PD have been shown to be effective in alleviating symptoms and controlling malignancies, but there is ongoing debate over whether DPPHR has an advantage over PD in terms of long-term benefits. METHOD:The authors searched the PubMed, Cochrane, Embase, and Web of Science databases for relevant studies comparing DPPHR and PD published before 1 May 2023. This study was registered with PROSPERO. Randomised controlled trials and non-randomised studies were included. The Mantel-Haenszel model and inverse variance method were used as statistical approaches for data synthesis. Subgroup analyses were conducted to evaluate the heterogeneity of the results. The primary outcome was the global QOL score, measured using the QLQ-C30 system. RESULTS:The authors analysed ten studies involving 976 patients (456 DPPHR and 520 PD). The global QOL score did not differ significantly between the DPPHR and PD groups [standard mean difference (SMD) 0.21, 95% CI (-0.05, 0.46), P =0.109, I2 =70%]; however, the OS time of patients with DPPHR was significantly improved [hazard ratio 0.59, 95% CI (0.44, 0.77), P <0.001, I2 =0%]. The follow-up length may be an important source of heterogeneity. Studies with follow-up length between two to seven years showed better global QOL for DPPHR than for PD [SMD 0.43, 95% CI (0.23, 0.64), P <0.001, I2 =0%]. There were no significant differences between the two groups in any of the functional scales of the QLQ-C30 system (all P >0.05). On the symptom scale, patients in the DPPHR group had lower scores for fatigue, nausea and vomiting, loss of appetite, insomnia, and diarrhoea than those in the PD group (all P <0.05). CONCLUSIONS:There were no significant differences in global QOL scores between the two surgeries; however, DPPHR had advantages over PD in terms of safer perioperative outcomes, lower long-term symptom scores, and longer OS times. Therefore, DPPHR should be recommended over PD for the treatment of benign pancreatic diseases and low-grade malignant tumours.

Wound healing is a sophisticated and orderly process of cellular interactions in which the body restores tissue architecture and functionality following injury. Healing of chronic diabetic wounds is difficult due to impaired blood circulation, a reduced immune response, and disrupted cellular repair mechanisms, which are often associated with diabetes. Stem cell-derived extracellular vesicles (SC-EVs) hold the regenerative potential, encapsulating a diverse cargo of proteins, RNAs, and cytokines, presenting a safe, bioactivity, and less ethical issues than other treatments. SC-EVs orchestrate multiple regenerative processes by modulating cellular communication, increasing angiogenesis, and promoting the recruitment and differentiation of progenitor cells, thereby potentiating the reparative milieu for diabetic wound healing. Therefore, this review investigated the effects and mechanisms of EVs from various stem cells in diabetic wound healing, as well as their limitations and challenges. Continued exploration of SC-EVs has the potential to revolutionize diabetic wound care.

Figure S2: IL-18 receptor (IL-18R) expression in pancreatic cancer tissues and cell lines.

Supplemental Material and Methods

Figure S4: IL-18 promotes PC cell proliferation, invasion and metastasis.

Figure S3: IL-18 promotes PC cell proliferation.

PDF file - 9152K, A. Wound healing assay for BxPC-3 cells after Tiam1 knock-down. B. Determination of BxPC-3 cell migration and invasiveness after Tiam1 knock-down using transwell assays. C. Determination of Panc-1 cell migration and invasiveness after Tiam1 knock-down using transwell assay. D. Transwell assays of invasiveness after treatment with NSC23766 and/or Y27632.

Figure S1: IL-18 is higher in PC tissues and correlates with poorer survival. Immunohistochemical (IHC) staining of IL-18

Figure S5: IL-18 promotes PC cell proliferation, invasion and metastasis.

PDF file - 11375K, A. Sorting of lentivirally transduced cell cultures to highest purity based on GFP expression. B. Western blot analysis of Tiam1 protein expression. C. Real-time RT-PCR analysis of Tiam1 mRNA expression. D. Rac1 activity determined by G-LISA assays. E. Western blotting for β-catenin in the cytoplasm and nucleus of panc-1 cells after transfection with si-rac1 or si-β-catenin or stimulation with NSC23766. F. CCK-8 analysis of cell proliferation after transfection with si-rac1 or si-β-catenin or treatment with NSC23766. G. EDU analysis of cell proliferation after transfection with si-rac1 or si-β-catenin or treatment with NSC23766.

Figure S6: IL-18 promotes proliferation and invasion of PC cells via the NF-κB pathway.