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Objective This study aimed to evaluate the effects of quercetin, paclitaxel, and cisplatin on the proliferation and migration of gastric cancer (GC) cells, focusing on the involvement of indoleamine 2,3-dioxygenase 1 (IDO1)-mediated tryptophan metabolism. Methods Human GC cell lines (AGS and MKN-45) were cultured and treated with quercetin, paclitaxel, or cisplatin for 24 h according to experimental group assignments. Following treatment, cell viability was assessed using the CCK-8 assay. Apoptosis and cell cycle distribution were analyzed by flow cytometry. Cell invasion was evaluated using the Transwell assay, and migration was assessed using the wound healing assay. Quantitative PCR (qPCR) was performed to determine mRNA expression levels of IDO1, tryptophan 2,3-dioxygenase (TDO), kynurenine 3-monooxygenase (KMO), and aromatic hydrocarbon receptor (AhR). Western blotting was used to quantify protein expression of IDO1, IDO2, TDO, KMO, and AhR. Results Treatment with quercetin, paclitaxel, or cisplatin significantly reduced cell viability, invasion, and migration, while increasing apoptosis in AGS and MKN-45 cells. These treatments were also associated with the downregulation of IDO1, IDO2, TDO, KMO, and AhR. Conclusion Quercetin, paclitaxel, and cisplatin exert anti-proliferative and anti-migratory effects on GC cells, potentially associated with the suppression of IDO1-mediated tryptophan metabolism.

Cholestatic liver diseases (CLD) are characterized by impaired normal bile flow, culminating in excessive accumulation of toxic bile acids. The majority of patients with CLD ultimately progress to liver cirrhosis and hepatic failure, necessitating liver transplantation due to the lack of effective treatment. Recent investigations have underscored the pivotal role of the gut microbiota-bile acid axis in the progression of hepatic fibrosis via various pathways. The obstruction of bile drainage can induce gut microbiota dysbiosis and disrupt the intestinal mucosal barrier, leading to bacteria translocation. The microbial translocation activates the immune response and promotes liver fibrosis progression. The identification of therapeutic targets for modulating the gut microbiota-bile acid axis represents a promising strategy to ameliorate or perhaps reverse liver fibrosis in CLD. This review focuses on the mechanisms in the gut microbiota-bile acids axis in CLD and highlights potential therapeutic targets, aiming to lay a foundation for innovative treatment approaches.

Background Hepatocellular carcinoma (HCC) is a prevalent primary liver malignancy and a leading cause of cancer-related mortality worldwide. Despite advancements in therapeutic strategies, the 5-year survival rate for individuals undergoing curative resection remains between 10% and 15%. Consequently, identifying molecular targets that specifically inhibit the proliferation and metastasis of HCC cells is critical for improving treatment outcomes. Database analysis using Targetscan identified complementary binding sites for the human-specific miRNA hsa-miR-6894-3p (hereafter referred to as miR-6894-3p) on SHROOM2, and Starbase data suggested a potential regulatory interaction between lnc-MAP3K13-3:1 and miR-6894-3p in liver cancer. Objective This study aimed to investigate the role of lnc-MAP3K13-3:1 in regulating miR-6894-3p, with a focus on its impact on proliferation, apoptosis, migration, and related cellular processes in liver cancer cells via SHROOM2 regulation. Methods Quantitative PCR (qPCR) was initially employed to measure the expression levels of lnc-MAP3K13-3:1 and miR-6894-3p in three HCC cell lines: HepG2, HuH-7, and Li-7. Based on these initial assessments, two cell lines were selected for further experimentation. Stable cell lines overexpressing lnc-MAP3K13-3:1 were developed, and cells were transfected with miR-6894-3p mimics or a mimic negative control (NC). After 24 h, qPCR was utilized to quantify the relative expression of lnc-MAP3K13-3:1, miR-6894-3p, SHROOM2, and Caspase9 mRNA in each group. Cell proliferation was analyzed using the cell counting Kit-8 assay, while flow cytometry was used to assess cell cycle distribution and apoptosis. Migration capabilities were evaluated through cell scratch assays, and dual-luciferase assays were utilized to verify interactions between miR-6894-3p, lnc-MAP3K13-3:1, and SHROOM2. Results Overexpression of lnc-MAP3K13-3:1 and miR-6894-3p mimic transfection resulted in increased expression of SHROOM2 and Caspase9 mRNA, as demonstrated by qPCR. The miR-6894-3p mimic regulated the activity of lnc-MAP3K13-3:1. Functional assays showed that lnc-MAP3K13-3:1 overexpression inhibited proliferation in HuH-7 and Li-7 cells, promoted apoptosis, reduced migration in Li-7 cells, but enhanced migration in HuH-7 cells. Additionally, lnc-MAP3K13-3:1 overexpression significantly increased the proportion of HuH-7 cells in the G2/M phase and Li-7 cells in the S phase. The miR-6894-3p mimic modulated the effects of lnc-MAP3K13-3:1 on cell proliferation, apoptosis, and migration. Dual-luciferase assays confirmed direct binding between lnc-MAP3K13-3:1 and miR-6894-3p, as well as between miR-6894-3p and SHROOM2. Conclusion These findings indicate that overexpression of lnc-MAP3K13-3:1 regulates SHROOM2 expression through targeting miR-6894-3p, thereby influencing cell proliferation, apoptosis, migration, and other cellular processes associated with HCC.

Biliary atresia (BA) is a severe inflammatory and fibrosing neonatal cholangiopathy disease characterized by progressive obstruction of extrahepatic bile ducts, resulting in cholestasis and progressive hepatic failure. Cholestasis may play an important role in the inflammatory and fibrotic pathological processes, but its specific mechanism is still unclear. Necroptosis mediated by Z-DNA-binding protein 1 (ZBP1)/phosphorylated-mixed lineage kinase domain-like pseudokinase (p-MLKL) is a prominent pathogenic factor in inflammatory and fibrotic diseases, but its function in BA remains unclear. Here, we aim to determine the effect of macrophage necroptosis in the BA pathology, and to explore the specific molecular mechanism. We found that necroptosis existed in BA livers, which was occurred in liver macrophages. Furthermore, this process was mediated by ZBP1/p-MLKL, and the upregulated expression of ZBP1 in BA livers was correlated with liver fibrosis and prognosis. Similarly, in the bile duct ligation (BDL) induced mouse cholestatic liver injury model, macrophage necroptosis mediated by ZBP1/p-MLKL was also observed. In vitro, conjugated bile acid-glycodeoxycholate (GDCA) upregulated ZBP1 expression in mouse bone marrow-derived monocyte/macrophages (BMDMs) through sphingosine 1-phosphate receptor 2 (S1PR2), and the induction of ZBP1 was a prerequisite for the enhanced necroptosis. Finally, after selectively knocking down of macrophage S1pr2 in vivo, ZBP1/p-MLKL-mediated necroptosis was decreased, and further collagen deposition was markedly attenuated in BDL mice. Furthermore, macrophage Zbp1 or Mlkl specific knockdown also alleviated BDL-induced liver injury/fibrosis. In conclusion, GDCA/S1PR2/ZBP1/p-MLKL mediated macrophage necroptosis plays vital role in the pathogenesis of BA liver fibrosis, and targeting this process may represent a potential therapeutic strategy for BA.

Since Vogt[1] recognized and classified the types of anomalies in 1929, many other classification systems have been proposed, including the Ladd, Gross, Swenson, and Kluth classification systems. [...]the illustration of the anatomical pattern of different types of EA/TEF was modified by close comparison with the original images from 434 patients with EA/TEF. According to our study, whether the proximal esophageal pouch is dilated may provide physicians with valuable insight into the diagnosis. [...]an accurate depiction of the gap length reveals why gastrotomy is preferred over primary anastomosis in type A and B patients. Because the distal esophageal remnant barely extends beyond the hiatus of the diaphragm, the gap between the pouches is too wide to be covered by one-stage reconstruction.

Background Esophageal atresia (EA) with concomitant hypertrophic pyloric stenosis (HPS) is a rare condition, and its diagnosis can be challenging due to overlapping postoperative complications. Comprehensive clinical characterization remains limited. Methods We retrospectively reviewed five patients with EA with concomitant HPS treated at our center between 2018 and 2025. A systematic literature search of PubMed, Embase, Web of Science, and CNKI identified 48 additional cases. Clinical features, timing of diagnosis, treatment strategies, and outcomes were analyzed. Results Among 132 neonates with EA in our institution, five (3.8%) developed HPS. Four had Gross type C EA, and three were male. All underwent EA repair in the first week of life and later developed HPS, diagnosed at a median age of 45 days (range: 20–145). All patients underwent laparoscopic pyloromyotomy with uneventful recovery and were alive at a median follow-up of 50 months. Literature review revealed 48 reported cases, predominantly male (41/48) and Gross type C (42/48). Combined analysis of 53 patients showed HPS onset typically between 2 and 15 weeks, with a median age of 4 weeks (IQR: 2.5–6 weeks). Overall survival was 90.6%, with deaths mainly due to infection or severe associated anomalies. Conclusions HPS may coexist with EA, with an incidence of approximately 3.8%. It often presents later in the disease course. Its diagnosis can be delayed by postoperative complications or altered feeding. Long-term follow-up and multicenter studies are warranted.

Background/Purpose This study aimed to evaluate discrepancies in prognosis after the Kasai portoenterostomy (KPE) procedure between neonatal and non-neonatal periods among patients undergoing the KPE procedure less than 60 days after birth (≤ 60 days). Methods All type III BA patients who performed KPE less than 60 days from June 2020 to May 2024 in the Department of Neonatal Surgery of Beijing Children’s Hospital were retrospectively reviewed. They were divided into two groups according to the age at Kasai: the early KPE group (EK group, or neonatal group ≤ 30 days after birth) and the late KPE group (LK group, or non-neonatal group 31–60 days after birth), to evaluate the effect of surgical age on the postoperative efficacy following Kasai. Results 61 BA patients were included in our study. The median age at KPE in the EK group was 14.0 [10.0, 20.0] days and 47.0 [36.8, 51.1] days in the LK group. Regarding postoperative complications, Patients in the EK group tended to have a higher incidence of postoperative intestinal obstruction (10.5% vs. 0.0%, p  = 0.033) compared to those in the LK group. However, the postoperative long-term prognosis of KPE in the EK group seemed much better than in the LK group. Compared to the LK group, a significantly greater proportion of patients in the EK group achieved successful jaundice clearance (84.2% vs. 40.5%, p  = 0.002) and successful bile acids clearance (63.2% vs. 19.0%, p  = 0.001). Additionally, the one-year NLS in the EK group was also higher than the LK group despite without statistically significant difference (88.2% vs. 61.5%, p  = 0.046). Kaplan-Meier curve also showed a significant difference between the two groups ( p  = 0.049, HR = 3.91, 95%Cl 1.46–10.46). Further, we evaluate the changes in biochemical indexes and liver hardness indicators over time in BA patients who had achieved one-year NLS. We found that compared to BA patients in the LK group, those in the EK group exhibited faster jaundice clearance and bile acids clearance, and more normalized biochemical indicators and liver hardness one year after Kasai. Conclusion Performing KPE procedure in the neonatal period was associated with a better long-term prognosis despite of potential increased risk of postoperative adhesive ileus.

Background In select patients with type C esophageal atresia, primary anastomosis is not appropriate and a staged approach is required. We aim to summarize our experience in the management of type C EA using a staged approach. Methods A retrospective chart-review of patients with type C EA admitted to Beijing Children’s Hospital between July 2020 to October 2023 were conducted. Those diagnosed with type C EA who were not amendable to primary anastomosis were included for analysis. Clinical information was recorded, and follow- up was performed. Results Seven (five boys) patients with type C EA who received staged repair were included in the study. Initial surgeries included thoracotomy and thoracoscopy. 71% (5/7) patient had complications after the initial surgery, including pyopneumothorax, pneumonia, recurrent tracheoesophageal fistula (rTEF), and anastomotic leak. Esophageal elongation techniques were applied in 3 patients. All delayed anastomosis were performed thoracoscopically, except for in one case where spontaneous fistulization occurred and no anastomosis were necessary. Complications after delayed anastomosis included recurrent esophageal pulmonary fistula (rEPF) in 50% (3/6), anastomotic leak in 33% (2/6), and esophageal stricture in all (6/6) patients. After a median follow-up of 14 months (range: 2–24), all patients were in generally good condition. Conclusion Primary operations should be kept simple and minimal in patients diagnosed with type C EA who are not appropriate for primary anastomosis. Internal traction is an effective method that allows for subsequent anastomosis. Intraoperative indocyanine green fluorescence can aid in fistula determination and anastomosis.

Background Recurrent tracheoesophageal fistula (rTEF) is a rare complication following initial esophageal atresia (EA) surgical repair, posing challenges in localization the fistula during surgery due to severe thoracic adhesions and structural ambiguity from previous operations. Objective We introduced two new localization methods for rTEF patients during surgery and aimed to compare the impact of using these localization techniques versus not using them on the surgical outcomes for rTEF patients. Methods We retrospectively analyzed the clinical data of rTEF cases that underwent thoracoscopic repair at our hospital from September 2017 to December 2024. Patients were divided into localization group and non-localization group based on whether using intraoperative localization techniques, and comparative analysis of clinical variables was conducted between groups. Results A total of 106 patients were included in this study, undergoing a total of 113 thoracoscopic rTEF repair surgeries at our center. Their fistula type included 89 cases of tracheoesophageal fistula (TEF), 19 cases of esophageal-pulmonary fistula (EPF), 3 cases of esophageal bronchial fistula (EBF), and 2 cases of combined EPF and TEF. All cases were categorized based on whether using localization techniques, resulting in the localization group ( n  = 52) and the non-localization group ( n  = 61). The median operation time in the localization group (2.5 h) was significantly lower than in the latter (3.0 h) ( P  = 0.001), and regardless of the fistula type being TEF or EPF. Additionally, the average postoperative hospital stay was significantly shorter in the localization group (17.7 ± 7.5 days) than in the non-localization group (23.6 ± 20.0 days) regarding the fistula type of TEF ( P  = 0.03). Conclusions The use of localization techniques in thoracoscopic surgery for rTEF leads to better outcomes, evidenced by reduced operation time and hospital stay, suggesting enhanced surgical accuracy and improved patient postoperative recovery. Level of evidence LEVEL III.

Revision surgery for the complications after repair of esophageal atresia is often complex because of previous surgeries and chest infections and thus requires surgical expertise. This study describes surgical experiences with the use of indocyanine green (ICG) fluorescence imaging localization-assisted thoracoscopy during revision surgery, including recurrent tracheoesophageal fistula (rTEF) (8 cases, one of which was esophageal-pulmonary fistula) and delayed esophageal closure (1 case). We performed fistula repair and esophageal reconstruction according to the indications of ICG. The application of this method avoids the excessive trauma caused by freeing the trachea and esophagus. Contrast imaging taken one week and one month after surgery indicated no spillover of the contrast agent from the esophagus, except in 1 case. Indocyanine green fluorescence imaging localization-assisted thoracoscopy is worth promoting for revision surgery after esophageal atresia repair.