Pancreatic cancer, one of the most malignant solid tumors with the poorest prognosis, is commonly treated with gemcitabine (GEM)-based systemic chemotherapy. However, chemoresistance remains a significant therapeutic challenge. Ferroptosis, a novel form of programmed cell death, has demonstrated exceptional susceptibility in chemoresistant cancer cells. Due to their unique magnetic responsiveness, iron oxide nanoparticles can generate heat under alternating magnetic fields, which enables magnetic hyperthermia (MH) therapy. This approach not only directly induces tumor cell apoptosis but also enhances chemosensitization. In this study, we demonstrate that ferrimagnetic vortex-domain iron oxide nanorings (FVIOs) as an ideal nanoplatform for MH, significantly improving GEM chemosensitivity in pancreatic cancer. Both in vitro and in vivo experiments demonstrated that MH not only synergizes with GEM to exhibit an antitumor effect in wild-type (WT) pancreatic tumors, but also directly suppresses the proliferation of gemcitabine-resistant (GR) counterparts while alleviating chemoresistance. High-throughput transcriptomic profiling revealed an increased susceptibility of GR cells to ferroptosis induction. Mechanistically, MH suppressed HSPB1 expression in GR cells, thereby attenuating its regulatory role in the ubiquitination-mediated degradation of ACSL4 protein and ultimately promoting ferroptosis. Comprehensive in vivo evaluations confirmed the multidimensional chemosensitizing efficacy of MH alongside favorable biosafety. Our findings highlight MH as a promising adjuvant strategy for pancreatic cancer, particularly in GEM-resistant cases, by overcoming chemoresistance through the potentiation of ferroptosis.

Background:Serum albumin is widely used in clinical practice as a nutrition-related biomarker, yet in sepsis its concentration is strongly influenced by inflammation, capillary leak, fluid redistribution, hepatic dysfunction, and exogenous albumin administration. Although hypoalbuminemia is consistently associated with poor outcomes, exogenous human albumin solution (HAS) has not shown a clear survival benefit in septic patients. We therefore investigated whether the prognostic significance of early serum albumin change differs according to whether the change is spontaneous or occurs in the context of HAS administration. Methods:We analyzed septic patients from the MIMIC-IV database and assessed consistency in an independent external cohort from the First Affiliated Hospital of Xi'an Jiaotong University. Delta albumin (ΔALB) was defined as the change in serum albumin during the first 3 ICU days. Patients were stratified according to HAS use during this period. The primary outcome was 90-day survival. Results:Among patients who did not receive HAS, higher ΔALB was significantly associated with lower 90-day mortality risk (HR per 1-g/dL increase = 0.50, 95% CI 0.40-0.62, p < 0.001), whereas this association was not observed in patients who received HAS. In the external cohort, the absence of a clear prognostic association in albumin-treated patients was directionally consistent, although validation of endogenous ΔALB was limited because most patients received HAS. Endogenous ΔALB was associated with baseline albumin, hematocrit change, platelet change, crystalloid volume, and liver-related variables, suggesting important influences of hemodilution, illness severity, circulatory status, and hepatic dysfunction. Conclusion:In the primary MIMIC-IV cohort, spontaneous increases in serum albumin, but not albumin changes among HAS-treated patients, were associated with better outcomes. These findings suggest that early albumin recovery should be interpreted cautiously in nutritional assessment, because its clinical meaning depends on albumin source and on non-nutritional physiological factors rather than nutritional status alone.

BackgroundMoyamoya disease (MMD) is a rare chronic occlusive cerebrovascular disorder associated with a high risk of perioperative ischemic or hemorrhagic stroke. Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant digestive system tumor with high surgical risk. The coexistence of MMD and PDAC is extremely rare, and no consensus on standardized perioperative management protocols has been established to date. The core clinical challenge lies in balancing the goal of radical tumor resection against the prevention of potentially devastating perioperative cerebrovascular events.Case presentationA 62-year-old Asian man with a 5-year history of asymptomatic MMD (managed with aspirin 100 mg daily) presented with painless obstructive jaundice and 5-kg unintentional weight loss. Imaging examinations demonstrated a 1.5 × 1.4 cm nodular lesion in the pancreatic head, which involved the intramural segment of the common bile duct and the duodenum. The preliminary diagnosis was pancreatic cancer. Cerebral computed tomography perfusion (CTP) showed compensatory cerebral blood volume elevation with a focal ischemic penumbra. The disease was classified as Suzuki stage III.Management and outcomesA multidisciplinary team (MDT) formulated an individualized perioperative strategy: (1) strict hemodynamic regulation with mean arterial pressure (MAP) maintained at 80–100 mmHg, (2) optimized anesthesia with continuous regional cerebral oxygen saturation (rSO2) monitoring, and (3) staged balanced anticoagulation with low-molecular-weight heparin (LMWH) bridging. The patient underwent standard pancreaticoduodenectomy (PD). The patient had an uneventful perioperative course, with no cerebrovascular events or major surgical complications. The final pathological examination confirmed moderately differentiated PDAC (pT1cN0M0, AJCC 8th edition) with R0 resection. During postoperative follow-up, the patient exhibited no tumor recurrence, neurological deficits, or cerebrovascular events.ConclusionFor patients with MMD undergoing radical PD, MDT-guided individualized management centered on cerebral perfusion maintenance, hemodynamic stability, and staged anticoagulation may help mitigate perioperative risks and achieve favorable clinical outcomes. This case provides practical experience for clinicians confronted with similarly rare clinical conditions. Given the inherent limitations of a single-case design, its generalizability remains to be validated in larger multicenter cohorts.

Perineural invasion (PNI) is a critical yet poorly understood feature that significantly influences the prognosis of pancreatic ductal adenocarcinoma (PDAC), a disease notorious for its dismal survival rates. Although PNI is recognized as a hallmark of pancreatic cancer, the molecular mechanisms underlying this process remain complex and incompletely defined. Recent insights into tumor-nerve interactions have highlighted the role of glycocalyx components, particularly mucin 15 (MUC15), in regulating neural invasion. In this study, we demonstrate that loss of MUC15 promotes PNI by activating the IGF1R/STAT3/NGF signaling axis. Specifically, reduced MUC15 expression weakens its interaction with IGF1R, leading to decreased receptor ubiquitination and increased phosphorylation, which in turn activates STAT3 signaling and drives NGF transcription and secretion. Loss of MUC15 also promotes epithelial-mesenchymal transition (EMT) and alters interactions with the tumor microenvironment, further facilitating neural invasion. Importantly, pharmacologic inhibition of IGF1R reverses these effects, suggesting that restoring MUC15 expression or targeting the IGF1R/STAT3-NGF axis may represent a potential therapeutic strategy to limit PNI in pancreatic cancer. These findings reveal a novel regulatory pathway connecting tumor-intrinsic signaling, EMT, and the neural microenvironment in PDAC progression.

OBJECTIVE:To determine whether robotic pancreatoduodenectomy (RPD) is non-inferior to open pancreatoduodenectomy (OPD) in terms of postoperative functional recovery, without compromising safety or oncological quality. DESIGN:Multicentre, single masked, phase 3, non-inferiority randomised controlled trial. SETTING:Seven tertiary high volume pancreatic centres in China, 15 June 2020 to 28 November 2024. PARTICIPANTS:268 adults with resectable pancreatic or periampullary disease. INTERVENTIONS:Participants were randomised to receive standardised RPD (n=142) or OPD (n=126), with enhanced recovery pathways. MAIN OUTCOME MEASURES:The primary outcome was time from surgery to postoperative functional recovery, defined as adequate pain control without parenteral analgesia, ≥50% oral intake without intravenous fluids, independent mobilisation, and absence of active intra-abdominal infection. The restricted mean event time (RMET) within 40 days was a summary for time from surgery to postoperative functional recovery. Secondary outcomes included operative metrics, disease related outcomes, length of stay, postoperative morbidity, including complications of Clavien-Dindo grade II or higher (defined as complications requiring drug treatment or more intensive intervention), and hospital admission costs. RESULTS:Overall, 254 of 268 randomly assigned participants (mean age 62 years; 172 (64.2%) men) underwent surgery, completed follow-up, and were included in the modified intention-to-treat population; 14 did not undergo surgery. In the modified intention-to-treat population, the RMET was 12.1 days (95% confidence interval (CI) 11.2 to 13.1) in the RPD group and 16.0 days (14.5 to 17.5) in the OPD group (difference -3.9 days, 95% CI -5.6 to -2.2; P<0.001). Operative time was longer in the RPD group (300 minutes (interquartile range (IQR) 240-360 minutes) versus 270 (210-300) minutes in the OPD group, P<0.001) but postoperative length of stay was shorter in the RPD group (13 (IQR 11-16) days v 16 (13-20) days, P<0.001). Overall postoperative morbidity was 31.1% (41/132) in the RPD group versus 36.1% (44/122) in the OPD group and incidence of any complications of Clavien-Dindo grade II or higher was 23.5% (31/132) versus 34.4% (42/122), respectively. 90 day mortality was 0.8% (1) in the RPD group and 2.5% (3) in the OPD group. Median total costs of hospital admission (including readmission cost) were higher in the RPD group than in the OPD group (¥130 905 (£14 369; $19 351; €16 628) (IQR ¥114 853-¥152 547) v ¥108 071 (¥92 134-¥128 035), difference ¥22 834 (95% CI ¥16 744 to ¥30 522); P<0.001). CONCLUSIONS:In high volume centres with credentialled surgeons, RPD met the non-inferiority margin for time from surgery to postoperative functional recovery, with comparable disease related outcomes and overall burden from postoperative complications. To generate wider system level efficiency gains, the implementation of RPD should take account of institutional expertise, procedural volume, acquisition of robotic surgical platforms and maintenance costs, and the potential for shorter hospital stay. TRIAL REGISTRATION:ClinicalTrials.gov NCT04400357.

Lung cancer remains one of the most prevalent and deadly malignant neoplasms worldwide, with smoking being a primary risk factor. Among the numerous carcinogens in tobacco smoke, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most potent. The carcinogenic effects of NNK are believed to be mediated through its metabolic activation by CYP2A13 in the lungs, leading to DNA adduct formation and subsequently lung cancer development. However, whether NNK exerts its carcinogenic effects by upregulating CYP2A13 expression and the mechanisms by which NNK upregulates CYP2A13 remain unclear. In this study, we demonstrated that CYP2A13 was overexpressed in human lung adenocarcinoma and NNK exposure significantly upregulated the expression of CYP2A13 in bronchial epithelial cells. Mechanistically, NNK exposure enhanced both transcription and stabilization of CYP2A13 mRNA. Further exploration showed that elevated transcription of CYP2A13 was mediated by the activation of the p-PP2A-C/p-JNK/p-c-Jun signaling axis, while CYP2A13 mRNA stability was driven through the S6/TRIM25/Dicer/miR-7108-3p axis. These findings not only provide critical insights into the mechanisms underlying NNK-induced lung carcinogenesis, but also identify potential therapeutic targets, including PP2A, TRIM25, and miR-7108-3p, for further exploration.

This study assessed the efficacy and safety of anlotinib plus transcatheter arterial chemoembolization (TACE) as adjuvant therapy in hepatocellular carcinoma (HCC) at high-risk recurrence after resection. This multi-center, single-arm, phase II study (ALTER-H004) enrolled patients with TACE-eligible HCC at high risk of recurrence after surgery. Three to five days after TACE, patients received 12 mg oral anlotinib once daily on days 1–14 every 3 weeks until recurrence, extrahepatic metastasis, or discontinuation was determined by investigators. Primary endpoint was disease-free survival (DFS). Twenty-nine patients were enrolled between April 2020 and August 2022. Median follow-up was 34.1 (IQR, 32.0–40.9) months. Of 27 with assessable efficacy, median DFS was 40.9 (95

Severe acute pancreatitis (SAP) is a life-threatening acute inflammatory disorder characterized by systemic inflammation and high mortality, for which specific targeted therapeutic strategies are still severely lacking in clinical practice. Mitochondrial dysfunction and impaired mitophagy have been validated as critical pathological drivers of SAP; nevertheless, the precise molecular targets governing the dysregulation of mitochondrial quality control remain poorly defined. Herein, we identify p38α (MAPK14) as a central regulator of mitophagy during SAP progression. Combining bioinformatic screening with an experimental SAP model, we demonstrate aberrantly hyperactivated p38α in pancreatic acinar cells. Mechanistically, activated p38α phosphorylates the S131 site of the E3 ubiquitin ligase Parkin. This site-specific phosphorylation triggers a “ubiquitination switch”, which selectively accelerates K48-linked polyubiquitination-dependent degradation of Parkin while impairing its K63-linked autoubiquitination and functional activity. Consequently, blockade of Parkin-dependent mitophagy results in accumulation of damaged mitochondria and massive leakage of mitochondrial DNA (mtDNA) into the cytoplasm, which further activates the cGAS-STING signaling cascade and exacerbates the sterile inflammatory storm. Pharmacological inhibition of p38α or genetic overexpression of the phosphorylation-deficient Parkin mutant (S131A) effectively restores mitophagic flux, eliminates cytoplasmic mtDNA accumulation, and suppresses cGAS-STING-mediated pro-inflammatory cytokine release, thereby markedly alleviating pathological injury in SAP. Our study illuminates a novel role of the p38α/Parkin/mtDNA/cGAS-STING signaling axis in the pathogenesis of SAP, and highlights targeting the p38α-mediated Parkin S131 phosphorylation switch as a promising therapeutic strategy for clinical intervention against SAP.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide, and accurate prognostic prediction remains highly challenging due to its marked biological heterogeneity and complex tumor microenvironment. To address this challenge, a histopathomics-based survival prediction system (HPSurv) was developed using histopathological whole-slide images (WSIs) for individualized overall survival (OS) prediction. Within this framework, pathological tissue classification, quantitative characterization of tumor spatial heterogeneity, and a survival Transformer were integrated to enable multi-level representation learning from histopathological data. The system was developed and evaluated in 1020 patients across five independent cohorts. Compared with conventional clinicopathological indicators, significantly improved prognostic performance was achieved across multicenter cohorts (p < 0.05), with a mean C-index of 0.761 and time-dependent AUCs of 0.936, 0.877, and 0.772 for predicting 6-month, 2-year, and 3-year survival, respectively. Subgroup analyses further supported its role as an independent prognostic factor and suggested its potential utility in stratifying patients with respect to ACT-related outcomes. In addition, significant associations with key PDAC molecular pathways were observed, providing biological insights into the model predictions and supporting interpretability. In the study, an interpretable and high-performing artificial intelligence (AI) framework for quantitative modeling of PDAC was established. Objective characterization of tumor heterogeneity and accurate postoperative survival prediction are enabled, with potential value for personalized management in PDAC.

BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) often presents with metastases. Brain metastases are rare, necessitating a thorough analysis of patient profiles and management. METHODS:Patients with PDAC and brain metastases (2010-2021) were identified from the SEER database. PDAC-specific survival (PSS) was the primary outcome. Survival differences were assessed via Kaplan-Meier analysis, and prognostic factors via Cox regression. RESULTS:This study included 113 patients with PDAC brain metastasis, and survival analysis was conducted on 78 eligible patients. The median PSS times were 6 months for brain metastases combined with lung metastases, 5 months for brain-only metastases, 3 months for brain metastases combined with bone metastases, 2 months for brain metastases combined with multiple metastases, and 1.5 months for brain metastases combined with liver metastases. Patients who received both radiotherapy and chemotherapy had better prognoses than those who had received radiotherapy only (P < 0.001, hazard ratio (HR) = 0.110). Other risk factors were combined with liver metastases (compared with only brain metastasis: P < 0.001, HR = 4.57) and a separated, divorced, or widowed marital status (compared with a married status: P = 0.038, HR = 2.029). CONCLUSIONS:Patients with PDAC brain metastases combined with liver metastases showed a significantly shorter median PSS time than those with brain metastases only. Patients who had received both chemotherapy and radiotherapy had longer median PSS time than those who had received radiotherapy only. A study with a large sample size is still required.

BACKGROUND:No clinically useful non-invasive biomarkers have been developed for diagnosis of chronic pancreatitis (CP), and molecular features of CP have not been characterised. Extracellular vesicles (EVs) consisted of abundant RNA species with specialised functions and clinical applications. OBJECTIVE:Our study aimed to construct a diagnostic model for CP and depict molecular landscape of CP based on EV long RNA (ExLR). DESIGN:Candidate ExLRs were defined using prespecified expression-quality criteria and complementary discovery-stage screens, and a resampling-based consensus feature selection in the training cohort yielded a five-ExLRs panel for model construction. The ExLRs-based CP diagnostic model (ExLRCPdscore) was further confirmed in another two independent validation cohorts with different controls. To elucidate the biological architecture of CP through ExLR profiling, we integrated ExLR-seq, single-cell data and clinical information. RESULTS:ExLRCPdscore constructed by random forest demonstrated excellent performance for detecting CP. Importantly, ExLRCPdscore could effectively detect early-stage CP, CP without alarm symptoms, CP without significant imaging findings and CP without risk factors. Using ExLR profiling and phenotypic data, we pinpointed MUC5B+ ductal cells exhibiting the strongest correlation with CP and derived an ExLR-based acinar-to-ductal metaplasia (ADM) score as a blood-based transcriptomic proxy of ADM-related programme. Integration of ExLR-seq and clinical information revealed significant associations between ADMscore and clinical characteristics, imaging findings and metabolic sequelae. CONCLUSION:Our study is the first to report an ExLRs-based diagnostic model that demonstrates exceptional robustness in differentiating CP from healthy controls and non-pancreatic disease controls. ExLRs offer a promising tool for CP molecular characterisation and pathophysiological quantification.

This study aims to explore the improvement effect of the WeChat-based School-Family-Hospital Collaborative Communication Mechanism (SFPC) on the teaching effectiveness and clinical practice competence of general surgical nursing interns, with a focus on the synergy between nursing practice and surgical diagnosis and treatment. It provides practical support for enhancing the integration of nursing education into general surgical clinical work. A prospective cohort study was conducted involving 132 general surgical nursing interns. Participants were allocated to a control group (receiving traditional teaching) and an observation group (undergoing the school-family-hospital collaboration [SFPC] teaching method) according to their school type and residential status, with 66 interns in each group. The medical interest scores of the SFPC teaching group were significantly higher than those of the traditional teaching group (P < 0.05). In addition, the SFPC teaching group showed statistically significant improvements in self-efficacy (P < 0.05), SEGUE communication ability (P < 0.05), inter-professional learning ability (P < 0.05), and simulated nurse licensure examination scores (P < 0.05). Notably, the intervention enhanced interns’ ability to collaborate with surgical physicians in clinical scenarios. This study confirms that the WeChat-based school-family-hospital collaborative mechanism significantly improves five core professional competencies of general surgical nursing interns, which is closely related to family support, and the guidance of nursing teachers and senior surgical physicians. It addresses the research gap in adapting nursing education to the long-cycle, multi-scenario characteristics of general surgical internships, and provides practical strategies for clinical nursing education integrated with surgical practice. This study provides evidence for using SFPC as an effective teaching method to improve various abilities and internship effects of general surgical nursing interns, especially their integration into surgical clinical work and collaboration with surgical teams. It offers practical strategies for the optimization of general surgical clinical nursing education.

BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterised by remarkable cellular heterogeneity, which emerges early from the interplay of oncogenic KRAS signalling and inflammatory injury. However, the transcriptional, metabolic and functional properties of these pre-malignant cell states that initiate and drive PDAC progression remain elusive. OBJECTIVE:This study aimed to identify and functionally characterise the critical premalignant cell states that arise from this heterogeneity, to define novel biomarkers and targets for early intervention. DESIGN:Public and in-house scRNA-seq data of pancreatic tumour models were analysed to identify key subpopulations in early cellular heterogeneity. Genetic perturbation in KrasG12D-driven models was performed to assess functional impact. Mechanistic studies used TurboID proximity proteomics, epigenetic profiling and metabolic assays. Clinical relevance was validated in human PDAC cohorts. RESULTS:We identified LY6D as a marker of a distinct, gastric-like cell state that emerges early and persists throughout tumourigenesis. The LY6D+ population exhibits conserved stemness and a unique, pan-stage dependency on oxidative phosphorylation (OXPHOS). Genetic ablation of Ly6d specifically impaired the gastric lineage and delayed tumourigenesis, while its overexpression enhanced tumourigenic and metastatic potential. Mechanistically, the glycosylphosphatidylinositol (GPI)-anchored LY6D protein scaffolds a lipid raft-associated kinase network that drives FOSL1-dependent epigenetic-transcriptional reprogramming. In human PDAC, LY6D+ cells harbour stemness and Epithelial-Mesenchymal Transition (EMT) signatures, and high LY6D expression is an independent prognostic marker of poor survival. CONCLUSION:Our work defines the LY6D+ gastric-like cell state as a key driver linking early pre-malignant heterogeneity to PDAC initiation and progression. LY6D represents a pan-stage therapeutic target and a candidate biomarker for early detection and therapeutic targeting.

Abstract Background: Patients in pancreatic surgery have a high incidence of malnutrition, and pancreaticoduodenectomy is a highly traumatic procedure that further impairs nutritional status. Chinese expert consensus on whole-course perioperative nutrition management in pancreatic surgery was published based on a national survey in 2020. This study aimed to evaluate the possible changes associated with the consensus over the past 5 years by conducting a nationwide cross-sectional survey among pancreatic surgeons in 2025. Methods: An online questionnaire survey was conducted among Chinese pancreatic surgeons. The questionnaire was divided into five sections: preoperative nutritional management, the placement of nutrition tube during operation, postoperative nutritional management, nutritional management for severe complications, and management of pancreatic exocrine and endocrine functions. Results: A total of 130 valid questionnaires were collected from 40 cities across 31 provinces and regions. Compared with the 2020 survey, the routine implementation rate of preoperative nutritional assessment increased from 62.5% (60/96) to 82.3% (107/130) ( P =0.002), the routine screening rate using Nutritional Risk Screening 2002 increased from 41.7% (40/96) to 65.4% (85/130) ( P <0.001), the participation rate of dietitians increased from 49.0% (47/96) to 70.0% (91/130) ( P =0.001), the intraoperative nasogastric tube placement rate decreased from 78.1% (75/96) to 56.9% (74/130) ( P <0.001). However, the rate of total parenteral nutrition application on the first postoperative day remained as high as 52.3% (68/130), while the proportion of early oral feeding was only 16.2% (21/130). Conclusions: Over the past 5 years, perioperative nutritional management in pancreatic surgery in China has made significant progress in standardization. However, certain differences still exist between clinical practice and consensus recommendations, requiring further promotion.

BackgroundAlthough current clinical guidelines recommend that patients who have undergone surgical resection for pancreatic cancer consider adjuvant chemotherapy options, a significant proportion of pancreatic cancer patients undergo surgical resection without receiving adjuvant chemotherapy. One key factor that contributes to this phenomenon is the uncertain effectiveness of adjuvant chemotherapy across various disease stages. The objective of this study was to explore the influence of postoperative chemotherapy on the prognosis of patients with different stages of pancreatic cancer.MethodsWe retrospectively analyzed the clinical data of 405 pancreatic cancer patients who underwent pancreatectomy between February 2016 and December 2020 in First Affiliated Hospital of Xi’an Jiaotong University. After excluding patients who did not undergo surgery, received other treatments, or died within 30 days postoperatively, 258 patients were included.96 received adjuvant chemotherapy and 162 did not. Early-stage (stage I, n=59) and late-stage (stages II-IV, n=199) were based on AJCC 8th edition. To minimize intergroup differences, propensity score matching (PSM) was performed. Overall survival (OS) was analyzed using the Kaplan-Meier method and Cox regression analysis.ResultsAmong the 258 patients, 187 died during follow-up, and the median survival was 14.9 months. Median follow-up was 36.5 months. In the overall cohort, patients receiving chemotherapy had longer median OS than those who did not (17.2 vs 13.3 months; P < 0.001). Chemotherapy significantly improved median survival in late-stage disease (15.6 vs. 11.9 months, P = 0.03), but not in stage I disease (28.0 vs. 27.0 months, P = 0.45). After propensity score matching, multivariable analysis confirmed that chemotherapy was independently associated with improved OS in late-stage disease (HR 0.59; 95% CI 0.38–0.91; P = 0.02). However, no significant survival benefit was observed in stage I patients (HR 0.69; 95% CI 0.27–1.77; P = 0.45).ConclusionsPatients with late-stage pancreatic cancer benefit from adjuvant chemotherapy after pancreatectomy. However, in patients with stage I pancreatic cancer, our data suggest that adjuvant chemotherapy may not confer a significant survival benefit.

Liver fibrosis, a critical pathological precursor of cirrhosis and hepatocellular carcinoma, represents a significant unmet global health challenge because of the lack of effective targeted therapies that can reverse established fibrotic scarring. An integrated strategy was employed. Network pharmacology was used to identify potential targets, followed by molecular docking and dynamics simulations. In vivo validation utilized two established murine models: carbon tetrachloride (CCl4) and bile duct ligation (BDL)-induced fibrosis. In vitro studies employed human LX-2 hepatic stellate cells to assess the antifibrotic effects on myofibroblasts. Huaier administration significantly attenuated liver fibrosis, improved liver function and reduced collagen deposition in both animal models. Histopathological analysis confirmed diminished inflammatory infiltration and fibrotic scarring. In vitro, Huaier suppressed LX-2 cell proliferation and migration. Bioinformatics and simulation analyses suggested AKT1 as a central target, with high-affinity binding with the bioactive steroidal components of Huaier. Mechanistically, Huaier specifically inhibited the phosphorylation and activation of the AKT signalling pathway in hepatic myofibroblasts. This study provides the first compelling evidence that Huaier granules alleviate liver fibrosis by targeting the AKT pathway to inhibit myofibroblast activation. These findings illuminate its mechanistic basis and suggest that Huaier is a promising, multitarget therapeutic candidate for combating fibrotic liver disease.

This study aims to evaluate the clinical outcomes of pancreaticoduodenectomy combined with longitudinal pancreatojejunostomy (PD-L) for chronic pancreatitis with a suspicious pancreatic head mass. We evaluated these derived surgical procedures with a focus on pain relief, functional preservation, and oncologic vigilance. This retrospective single-center cohort study analyzed clinical data from 20 consecutive patients diagnosed with chronic pancreatitis who underwent PD-L at the Hepatobiliary Surgery Department of the First Affiliated Hospital of Xi’an Jiaotong University between December 2021 and December 2024. We systematically analyzed perioperative parameters, morbidity profiles, and histopathological characteristics. Post-discharge monitoring focused on quantitative pain assessment, pancreatic exocrine and endocrine functional status, and surveillance. The patients’ cohort comprised 20 male patients (mean age 52.3 ± 10.1 years, range 32–70) who underwent PD-L procedures: open (n = 15), laparoscopic (n = 3), and robotic-assisted (n = 2) approaches. The mean operative time was (387.7 ± 75.1) minutes, with an average intraoperative blood loss of (286 ± 141.0) mL. The mean total length of hospital stay was (18.9 ± 4.6) days. Postoperative complications occurred in 2 patients: one case of abdominal hemorrhage requiring angiographic embolization and one case of delayed gastric emptying managed through endoscopic drainage. Notably, no pancreatic fistula were observed in any case. Pathology revealed chronic pancreatitis in 9 patients, PanIN in 9 (6 PanIN-1, 3 PanIN-2), and pancreatic cancer in 2. Preoperative comparisons between the CP group (n = 9) and the PanIN/malignant group (n = 11) showed no significant differences. Although considerable differences in the smoking index were observed between the two groups, they did not reach statistical significance (p = 0.081). During a median follow-up of 14.5 months, 78.9

Due to its high recurrence and metastasis rates, the prognosis of pancreatic cancer (PC) patients is extremely poor. Cancer stem cells (CSCs) are the major source of occurrence and progression of PC, suggesting that targeting pancreatic CSC stemness may provide therapeutic benefits. This study aims to clarify the mechanisms by which Honokiol (HNK) inhibits the stemness of pancreatic cancer. The expression of c-Met and downstream molecules was investigated based on public databases and also confirmed by the immunohistochemistry (IHC) staining of human tissues. Colony formation assay and sphere formation assay were conducted to verify the effect of HNK on the proliferation and stemness of PC cells. A subcutaneous transplanted tumor model of BALB/c nude mice was established to explore the effect of HNK on modulating the tumor growth of PC in vivo. c-Met expression was significantly elevated in PC tissues versus normal pancreas tissues, and the high level of c-Met was positively correlated with poor prognosis of PC patients. Overexpression of c-Met significantly enhanced the proliferation and stemness of cancer cells, whereas HNK treatment reversed these effects. Critically, HNK suppressed tumor growth in vivo by downregulating c-Met. Our study reveals that HNK reduced the proliferation and stemness of PC cells via suppressing the c-Met overexpression. These findings provide a potential therapeutic method for PC, offering new hope for improving patients' outcomes.