Xiaobo Cai

A 72-year-old woman underwent local resection for a pancreatic serous cystadenoma ([Fig. 1]). A single-pigtail pancreatic duct stent (Micro-Tech, 5 Fr*7cm) was placed preoperatively via endoscopic retrograde cholangiopancreatography (ERCP; [Fig. 2]). Subsequently, she underwent local pancreatic resection and T-tube placement in the bile duct. Three months postoperatively, a computed tomographic (CT) scan revealed that the stent had migrated to the tail of the pancreas and appeared significantly shortened, suggesting stent fracture ([Fig. 3]). A subsequent ERCP was performed for stent retrieval. Pancreatography demonstrated stenosis and deformity of the pancreatic duct at the neck, along with contrast extravasation and opacification of the bile duct, increasing the possibility of a pancreaticobiliary fistula. After difficult cannulation with a standard guidewire, a super-fine curved guidewire (Olympus VisiGlide 2) was successfully advanced into the pancreatic duct ([Fig. 4]). The stenotic segment was dilated with a 4 mm × 6 cm balloon (Hurricane, Boston Scientific). A cholangioscope (EyeMAX, 9 Fr) was then introduced, traversing the narrowing and identifying the fractured stent fragment within the pancreatic duct. The retained stent was successfully grasped under direct vision using SpyBite MAX biopsy forceps (Boston Scientific) and retrieved along with the cholangioscope ([Video 1], [Fig. 5]). A new stent was placed in the pancreatic duct. The patient had an uneventful recovery and was discharged 3 days postoperatively. Stent migration within the pancreatic duct is rare, with a reported incidence of approximately 0.2%. Stent fracture is also uncommon; one study reported an incidence of 1.2%, although all cases involved straight stents that fractured during removal due to pancreatic duct stenosis [1] [2]. This is the first reported case of a surgical-related pancreatic duct stent fracture with proximal migration. The presence of pancreatic duct distortion and stenosis rendered the retrieval procedure particularly challenging. The use of cholangioscopy-guided intervention proved effective for the successful and safe removal of the migrated stent fragment. Endoscopy_UCTN_Code_CPL_1AK_2AD Article published online: 16 January 2026 © 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/). Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

Capillarization of liver sinusoidal endothelial cells (LSECs) is a central event in response to liver injury. In this study, we investigated the role of Yes-associated protein 1 (YAP1, also known YAP) in LSEC capillarization and liver injury. YAP expression was assessed in liver samples from mice injured by CCl4 injection and DDC diet. EC-specific Yap1 conditional knockout mice (Yap1∆end) were generated by breeding Yap1fl/fl mice with Cdh5-CreERT2 mice. HA-PEI/siYap1 nanoparticles were applied to specifically inhibit YAP expression in LSECs. YAP was primarily expressed in LSECs, and its expression was elevated during liver fibrosis. EC-specific Yap1 deficiency significantly increased the fenestrae in LSECs and mitigated hepatocyte death and liver fibrosis. Overexpression of YAP in EC aggravated capillarization, hepatocyte death, and liver fibrosis. Mechanistically, YAP inhibited Gata6 transcription via binding to its promoter and thus resulted in LSEC capillarization. Overexpression of GATA6 in EC alleviated capillarization and liver fibrosis by activating Nos3 transcription. Moreover, specific delivery of HA-PEI-siYap1 nanoparticles to LSEC alleviated liver injury in mice. YAP-GATA6/eNOS signaling is essential in LSEC capillarization and subsequent hepatocyte death. Interventions targeting YAP in LSECs offer a promising strategy for the treatment of liver fibrosis. YAP expression in LSEC is upregulated in injured mice. Deletion/overexpression of Yap1 in LSECs attenuates/aggravates capillarization, hepatocyte death, and liver injury in mice, respectively. YAP inhibits Gata6 transcription via binding to its promoter and results in LSEC capillarization through GATA6/eNOS-dependent pathway. Delivering siYap1 to LSEC via nanoparticles represents a new approach for treating liver fibrosis.

Currently, the treatment of Metabolic dysfunction‐associated fatty liver disease (MASLD) is limited, and this research aimed to investigate the therapeutic effect and molecular mechanism of Hydronidone (HDD) on MASLD. In our research, High fat and High cholesterol diet (HFHC) as well as Methionine‐Choline Deficient diet (MCD) were used to establish the MASLD mouse model. Palmitic Acid (PA)‐induced mouse primary hepatocytes (mpHCs) and AML12 cell line were used as cell model. The animal model was treated with three doses of HDD (25/50/100 mg/kg), and the cell model was treated with 0/50/100/200/400 μM HDD respectively. The therapeutic effect of HDD on MASLD models was observed by tissue staining, biochemical tests, qPCR, and Western Blot. Transcriptome sequencing was conducted among the normal control group (NCD group), model group (HFHC group) and medium‐dose HDD treatment group (HFHC + 50 mg/kg HDD), through which CD36 was identified as a potential effector gene of HDD. Then, CD36 was overexpressed in the liver by adeno‐associated virus on the basis of HFHC+HDD treatment model, and the effects of overexpression of CD36 on HDD treated MASLD mice were observed. The results showed mice in the HDD treatment group had significant improvements in liver steatosis, inflammation, and fibrosis compared with the model group (HFHC/MCD group). Lipid deposition in mpHCs and AML12 cells treated with PA was also significantly reduced after HDD intervention. The results of transcriptome sequencing showed that the expression of genes involved in lipid synthesis, inflammation, and fibrosis were significantly changed in the HDD treatment group. Overexpression of CD36 blocked the therapeutic effect of HDD on MASLD models. HDD could alleviate the disease progression by inhibiting the expression of CD36 in MASLD mice and cell models.

Background and Aim: Hydronidone (HDD) is a novel pirfenidone derivative developed initially to reduce hepatotoxicity. Our previous studies in animals and humans have demonstrated that HDD treatment effectively attenuates liver fibrosis, yet the underlying mechanism remains unclear. This study aimed to investigate whether HDD exerts its anti‐fibrotic effect by inducing apoptosis in activated hepatic stellate cells (aHSCs) through the endoplasmic reticulum stress (ERS)‐associated mitochondrial apoptotic pathway.Methods: The carbon tetrachloride (CCl₄)‐ and 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC)‐induced liver fibrosis models were used for in vivo studies. In vitro studies were conducted using the human hepatic stellate cell line LX‐2. The apoptotic effect of HDD on aHSCs was examined using TUNEL and flow cytometry assays. The small interfering RNA (siRNA) technique was employed to downregulate the expression of interest genes.Results: HDD treatment significantly promoted apoptosis in aHSCs in both the CCl₄‐ and DDC‐induced liver fibrosis in mice and LX‐2 cells. Mechanistic studies revealed that HDD triggered ERS and subsequently activated the IRE1α‐ASK1‐JNK pathway. Furthermore, the influx of cytochrome c from the mitochondria into the cytoplasm was increased, leading to mitochondrial dysfunction and ultimately triggering apoptosis in aHSCs. Notably, inhibition of IRE1α or ASK1 by siRNA partially abrogated the pro‐apoptotic effect of HDD in aHSCs.Conclusions: The findings of both in vivo and in vitro studies suggest that HDD induces apoptosis in aHSCs via the ERS‐associated mitochondrial apoptotic pathway, potentially contributing to the amelioration of liver fibrosis.

INTRODUCTION: Although cytologic examination of biliary stricture brushings obtained by endoscopic retrograde cholangiopancreatography is commonly used for diagnosing malignant biliary strictures (MBSs), it has low sensitivity. Several new brushes have capabilities that are still being debated. We have developed a novel brush working from conventional back-and-forth movement to rotation in situ (RIS) that may be more efficient for MBS sampling. We aimed to compare the MBS detection sensitivity of our RIS brush with that of the conventional brush. METHODS: In this multicenter prospective study, we enrolled patients who underwent endoscopic retrograde cholangiopancreatography for suspected MBSs involving biliary stricture brushings obtained using our RIS brush. The historical control group consisted of the 30-brushing arm of our previous randomized trial (patient inclusion, 2018–2020) that used the study design in the same centers and with the same endoscopists as were used in this study. The primary outcome was to compare the sensitivity and specificity of detecting MBSs by cytologic evaluation of biliary stricture brushings between the 2 groups. RESULTS: We enrolled 155 patients in the intent-to-treat analysis. Using the same number of brushing cycles, the RIS brush showed a higher sensitivity than the conventional brush (0.73 vs 0.56, P = 0.003). In per-protocol population, the sensitivity was also higher in the RIS brush group than in the conventional brush group (0.75 vs 0.57, P = 0.002). Multivariate analysis revealed that the RIS brush was the only predictive factor for MBS detection. No significant differences were observed in procedure-related complications between the 2 groups. DISCUSSION: The RIS brush was a promising tool for effective and safe MBS sampling and diagnosis. Further randomized studies are warranted to confirm our results (Chictr.org.cn, identifier: ChiCTR2100047270).

Chronic liver disease has emerged as a significant global concern, with primary hepatocellular carcinoma (HCC) representing a critical consequence of this disease. However, early detection of HCC remains challenging in clinical practice. Recently, there has been a growing interest in applying endoscopic ultrasound (EUS) as a diagnostic tool for gastrointestinal diseases. Nevertheless, using EUS to diagnose and treat HCC is uncommon. In this review we described the diagnostic and therapeutic applications of EUS in primary HCC and evaluated its clinical significance. The diagnostic procedures primarily involve EUS-guided fine-needle biopsy or aspiration, assessment of metastatic lymph nodes and portal vein thrombosis, portal pressure monitoring, and portal vein blood collection. Treatment mainly includes EUS-guided tumor ablation, brachytherapy, injectable chemotherapy, and managing variceal hemorrhage related to portal hypertension. Chronic liver disease has emerged as a significant global concern, with primary hepatocellular carcinoma (HCC) representing a critical consequence of this disease. Early detection of HCC is still challenging in clinical practice. In this review, we described the diagnostic and therapeutic applications of endoscopic ultrasound (EUS) in primary HCC and evaluated its clinical significance. The diagnostic procedures primarily involve EUS-guided fine-needle biopsy or aspiration (FNB/FNA), assessment of metastatic lymph nodes and portal vein thrombosis (PVT), portal pressure monitoring, and portal vein blood collection. And the management strategies mainly include EUS-guided tumor ablation, brachytherapy, injectable chemotherapy, and managing variceal hemorrhage related to portal hypertension in HCC. EGVB, esophagogastric variceal bleeding. image

Liver fibrosis is closely related to the proliferation and differentiation of liver progenitor cells (LPCs). Yes‐associated protein (YAP) is a key effector molecule of the Hippo signaling pathway and plays an important role in regulating cell proliferation and liver homeostasis. However, its role in LPCs proliferation and differentiation during liver fibrosis are not well understood. Using immunohistochemistry, immunofluorescence staining, quantitative PCR and Western blotting, we discovered that LPCs expansion and enhanced YAP expression in LPCs in either choline‐deficient, ethionine‐supplemented (CDE) diet or 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC) diet‐induced fibrotic mice, as well as in patients with liver fibrosis. By injecting adeno‐associated virus vectors under the transcriptional control of Lgr5 promoter, we found that targeted knockdown of YAP in LPCs attenuated the CDE/DDC diet‐induced ductular reaction and liver fibrosis. Using EdU incorporation and Cell Counting Kit‐8 assays, we demonstrated that YAP can modulate LPCs proliferation. Importantly, spleen transplantation of YAP‐overexpressing LPCs improved their ability to differentiate into hepatocytes and alleviated carbon tetrachloride‐induced liver fibrosis. Collectively, our findings indicate that LPCs expansion and differentiation during liver fibrosis could be modulated by YAP, further suggesting the possibility of manipulating YAP expression in LPCs as a potential treatment for chronic liver diseases.

Liver fibrosis is a pathological response driven by the activation of hepatic stellate cell (HSC). However, the mechanisms of liver fibrosis and HSC activation are complicated and far from being fully understood. We aimed to explore the candidate genes involved in HSC activation during liver fibrogenesis. Five genes (LBH, LGALS3, LOXL1, S100A6 and SPP1) were recurrent in the DEGs derived from the seven datasets. The expression of these genes gradually increased as liver fibrosis staging advanced, suggesting they might be candidate genes involved in HSC activation during hepatic fibrosis. These candidate genes were predicted to be coregulated by miRNAs such as hsa-miR-125a-5p and has-miR-125b, or by transcription factors including JUN, USF1, TP53 and TFAP2C. PPI analysis showed that LGALS3, LOXL1, S100A6 and SPP1 might interact with each other indirectly, but no interaction was found between them and LBH. The candidate genes and their interaction partners were enriched in focal adhesion, extracellular matrix organization and binding. Upregulation of LBH, S100A6 and SPP1 were further validated in TGF-β-treated LX-2 as well as in DDC or CCL₄-treated mice models. Decreased LBH and SPP1 expression reduces the expression of HSC activation-related markers in TGF-β-treated LX-2. Our results indicated that LBH, LGALS3, LOXL1, S100A6 and SPP1 were candidate genes which may participate in the HSC activation during liver fibrosis.