Objective To explore the mechanism by which zinc-regulated transporters, iron-regulated transporter-likeprotein 4 (ZIP4) regulates glycolysis and its impact on tumor progression in cholangiocarcinoma (CCA), providing a theoretical basis for targeted therapy of CCA. Methods ZIP4 expression in CCA was analyzed using the GEPIA database. Immuno-histochemistry (IHC) was used to detect ZIP4 expression in 20 paired CCA and adjacent non-tumor tissues. Stable ZIP4-overexpressing CCA cell lines (ZIP4-OE) were established. Gene set enrichment analysis was used to screen differentially expressed genes and pathways in ZIP-OE CCA cells. ZIP4, N-myc proto-oncogene protein (MYCN), and histone-lysine N-methyltransferase 2E (KMT2E) were knocked down using small interfering RNAs (siRNAs). The expression of glycolysis-related gene (glucose transporter 1 [Glut1], hexokinase 2 [HK2], and lactate dehydrogenase A [LDHA]) was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Glycolytic activity was assessed by measuring the extracellular acidification rate (ECAR). Cell proliferation was evaluated using colony formation assays, and cell migration was assessed using Transwell assays. A xenograft mouse model was constructed to examine CCA tumor growth. Protein levels of ZIP4, KMT2E, H3K4me3 (tri-methylation of lysine 4 on histone H3), and MYCN were detected by Western blotting. Results GEPIA database analysis and IHC results confirmed significantly higher ZIP4 expression levels in CCA tissues compared to adjacent non-tumor tissues (P＜0.05). Compared to the control group, the ZIP4-OE group exhibited a significantly increased ECAR, along with significantly enhanced proliferation and migration abilities (P＜0.01). Conversely, knockdown of ZIP4 suppressed CCA cells proliferation and migration. GEPIA analysis indicated that ZIP4 upregulates the transcription of oncogene MYCN, as well as glycolysis-related genes. Knockdown of MYCN abolished the ZIP4 overexpression-induced upregulation of Glut1, HK2, and LDHA gene transcription, reduced glycolysis, and significantly inhibited CCA cell proliferation and migration (P＜0.05). Mechanistic studies demonstrated that ZIP4 increases H3K4me3 level via KMT2E, leading to MYCN transcription. Knockdown of KMT2E in CCA cells suppressed the ZIP4 overexpression-induced enhancement in H3K4me3 modification, resulting in MYCN downregulation and significantly reduced CCA cells proliferation and migration (P＜0.05). Conclusions ZIP4 upregulates H3K4me3 modification through KMT2E, which recruits transcription factors to activate the transcription of MYCN. This subsequently enhances cellular glycolysis and promotes the proliferation and migration of CCA cells.

Objective To establish a cell bank of extrahepatic cholangiocarcinoma (ECC)-derived organoids and investigate the key factors influencing the organoids generation. Methods The tumor samples from patients with portal cholangiocarcinoma (pCCA) and distal cholangiocarcinoma (dCCA) were used to isolate cells, and these cells were cultured using three-dimensional (3D) technique to establish ECC organoids. Histological characteristics of the organoids were evaluated and identified through hematoxylin-eosin (HE) and immunohistochemistry stainings. The success rates of organoids generation from different tumor types were compared. And clinical characteristics of patients between successful and failure culture groups were compared. Results The success rates of organoids establishment from pCCA and dCCA were all low, with 42.4% (14/33), 51.9% (14/27), respectively. The tumor was larger in successful group than that in failure group (P＜0.001); there was no statistical difference in tumor differentiation status, microvascular invasion, and perineural invasion between the two groups. Conclusions The successful rate of ECC-derived organoids establishment is low, and larger tumor has higher successful culture rate.

Objective To evaluate the clinical efficacy and application value of digital subtraction angiography (DSA) in the management of delayed pancreaticoduodenectomy(PD) hemorrhage(PPH).Methods A retrospective analysis was conducted on the clinical data of 38 patients who underwent DSA for delayed PPH at Zhongshan Hospital, Fudan University, between January 2019 and December 2024. The technical success rate and clinical outcomes of interventional treatment were the primary focus of the evaluation.Results Among 726 patients who underwent PD, 38 (5.2%) experienced delayed bleeding. Of these, 30 (78.9%) showed positive findings on DSA. The distribution of bleeding sites was as follows: gastroduodenal artery (18 cases), common hepatic artery (1 case), the first branch of the jejunal artery (2 cases), proper hepatic artery (2 cases), right hepatic artery (1 case), middle hepatic artery (1 case), left hepatic artery (3 cases), origin of the splenic artery (1 case), and right gastroepiploic artery (1 case). Interventional treatments included microcoil embolization (17 cases), microcoil combined with gelatin sponge embolization (4 cases), covered stent implantation (7 cases), and gelatin sponge embolization alone and microspheres embolization (1 case each). Successful hemostasis was achieved in 28 (93.3%) patients through DSA-guided interventional treatment, while 2 patients required surgical hemostasis due to recurrent bleeding.Conclusions DSA-guided interventional embolization offers advantages such as minimal invasiveness, precise localization, and effective hemostasis, making it the preferred treatment strategy for delayed PPH.

Objective To report cases of checkpoint inhibitor pneumonitis （CIP） in patients with advanced biliary tract cancer, aiming to provide additional approaches for the assessment, treatment, and monitoring of this condition. Methods Three patients developed oxygen desaturation and interstitial lung lesions during chemotherapy combined with immunotherapy, and were diagnosed with CIP in collaboration with the respiratory department. Antitumor therapy was discontinued in the acute phase, and glucocorticoids were administered, with regular monitoring of disease progression. During follow-up, case 1 developed lung metastasis; case 2 showed improvement; case 3 had concurrent infection and tumor progression. Results Glucocorticoids improved lung lesions and hypoxic symptoms in patients with CIP, but attention should be paid to the potential for concurrent infections and tumor progression. Conclusions Comprehensive assessment and early identification of CIP are crucial for patients with advanced biliary tract cancer. For those with recurrent symptoms after glucocorticoid therapy, timely and accurate adjustment of the treatment regimen is essential.

Purpose: The aim of the present study was to test the hypothesis that recovery sleep could counteract the detrimental effects of sleep deprivation (SD) on male rats’ fertility. Materials and Methods: Twenty-two rats were housed in groups of six per cage with unrestricted access to food and water in a room. The modified multiple platform method was used to induce SD in rats over a 96-hour period. We examined the effect of SD on semen quality, reproductive hormones, and testicular histology in adult male rats. Then, we investigated the effect of 7 days recovery sleep on impaired reproductive function induced by SD. Results: After the acclimation period, 22 rats were randomly separated into three experimental groups (SD, recovery sleep, and the control groups). Ninety-six hours of SD resulted in a significant decrease in sperm motility (24.33±10.93 vs. 48.20±8.55, p<0.001) and the number of morphologically normal sperm (9.68±2.77 vs. 26.21±14.60, p<0.01) in rats, accompanied by a decrease in testosterone levels (1.53±0.55 vs. 4.44±0.56, p<0.001) and destruction of testicular tissue structure compared with control group. After 7 days of recovery sleep, semen quality, especially sperm motility, was improved and testosterone levels were significantly higher compared to post-SD (3.70±0.53 vs. 1.53±0.55, p<0.05), but remained low compared to the control group. Conclusions In conclusion, 96 hours of SD deteriorated the parameters of sperm motility and the number of morphologically normal sperm in rats, probably due to the decrease in serum testosterone levels and the disruption of testicular tissue structure when compared to the control group. After 7 days of recovery sleep, semen parameter, especially sperm motility and testosterone levels did not return to baseline levels compared to the control group.

Benign gallbladder diseases are common diseases in general surgery, including gallstones, polypoid lesions, cholecystitis, etc. In China, the treatment of benign gallbladder diseases is still not standardized, which mainly shows in following aspects: (1)the tendency of cholecystectomy to all gallbladder diseases may result in the incidence of abdominal pain, distension, diarrhea and bile duct injury after surgery; (2)the attitude of "no-surgery" in which the standard cholecystectomy fails to implement in time for the benign gallbladder diseases with potential high-risk factors for gallbladder cancer, as a result, patients develop occurrence of gallbladder cancer. Especially, gallbladder sparing surgery is an unscientific surgery for benign gallbladder diseases, the gallbladder may become a high-risk factor for cancer after the operation. Implementation of standard cholecystectomy in time for benign gallbladder diseases with potential high risk gallbladder cancer can not only significantly reduce the incidence of gallbladder cancer, but also significantly improve the early diagnosis and the prognosis. Based on current literatures, the authors analyze the treatment status of benign gallbladder diseases, and investigate the disputes and problems in surgical indications, operation time and the selection of treatments of benign gallbladder diseases.

Iron is an important nutrient element which is involved in a variety of physiological processes. The potential toxicity of excess iron requires that cells should evolve a robust, tightly regulated mechanism for maintaining iron homeostasis. At the same time, iron plays an indispensable role in the process of tumorigenesis and progression. The mechanism involved in iron homeostasis can make changes to adapt to its metabolic level and to maintain the activity of the tumor cells. This paper reviews iron metabolism and its role in the maintaining of iron homeostasis, as well as the importance of iron metabolism in solid cancers.

Objective To study the use of preoperative indocyanine green retention test at 15 minutes (ICG R15) in the prediction of liver functional reserve in patients with hilar cholangiocarcinoma (HCCA).Methods The clinical data of 62 patients with HCCA treated in our department from March 2016 to March 2018 was reviewed.The relationship between preoperative ICG R15 and postoperative hepatic insufficiency was analyzed.The relationship between preoperative ICG R15 and Child-Pugh scoring was also studied.Univariate analysis was used to evaluate the risk factors of postoperative liver dysfunction.Logistic regression was used to assess the independent risk factors of postoperative liver dysfunction.The regression equation between independent risk factors and postoperative liver dysfunction was established.Results Among the 62 patients,ICG R15 was less than 10.0％ in 26 patients,between 10.0％ and 19.0％ in 17 patients,between 20.0％ and 29.0％ in 9 patients,between 30.0％ and 39.0％ in 5 patients,and over 40.0％ in 5 patients.There were 29 patients with a Child-Pugh A grading and 33 patients with a Child-Pugh B grading in the preoperative evaluation of liver function.The Wilcoxon W rank sum test was used to compare the preoperative ICG R15 in patients with Child-Pugh grading A and B separately.The ICG R15 in Child-Pugh grading A patients was significantly lower than those in Child-Pugh B grading patients (P ＜0.05).There were no significant differences in age,gender,history of previous liver diseases,duration of operation,and intraoperative blood loss (P ＞ 0.05) between the normal liver function group and the liver dysfunction group.However,there was a significant difference in the preoperative ICG R15 and preoperative bilirubin levels (P ＜ 0.05) between the two groups.The preoperative ICG R15 and preoperative bilirubin levels were significant risk factors of postoperative hepatic insufficiency.Regression analysis suggested that preoperative ICG R15 level was an independent risk factor of postoperative hepatic insufficiency (P ＜ 0.05).A regression equation:logit(P) =0.185 × preoperative ICG R15-3.152 could be constructed.Conclusions ICG R15 is an ideal clinical indicator for evaluation of preoperative liver functional reserve in patients with HCCA.It predicted the recovery of postoperative liver function.

Preoperative biliary drainage (PBD) is an important part of preoperative management of patients with hilar cholangiocarcinoma which could reduce serum total bilirubin,remove jaundice,improve liver function,and reduce the mortality and morbidity.Although PBD is widely used in biliary surgery now,there are still several controversial issues in clinical applications about the indication of PBD,the best way of PBD,implantation metastasis of PBD and so on.With the development of medical image and surgical technology,we had a better understanding of PBD now.This review summarizes the recent scenario and current advancement about the above-mentioned controversy.

ObjectiveTo provide clues to find a biomarker for early diagnosis, prognosis and therapy, as well as to understand the molecular mechanisms governing cancer progression. Methods Surgical specimens were obtained from 87 patients with histopathologically proven malignant or benign lesions. The differential protein profiles of these malignant and benign specimens were detected using two-dimensional electrophoresis (2-DE) combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Western blotting and immuno-histochemistry were used to validate the results. RT-PCR was used to detect the gene expression in the tissues. ResultsMrp14 was found to be overexpressed in the tumor tissues of gallbladder cancer and extra-hepatic bile duct cancer, and in the bile of patients with malignant biliary tract tumours. The result was further verified using Western blot and immuno-histochemistry. RT-PCR confirmed the overexpression of Mrpl4 at the gene level. Mrp14 is a potential biomarker for biliary tract neoplasms. ConclusionsThis is the first report which described the overexpression of Mrp14 in biliary tract neoplasms and further studies are needed to confirm our findings. Mrp14 may be a potential hiomarker for biliary tract neoplasms. It may provide important clues on the molecular mechanisms governing cancer progression.