Objective:To investigate the main causes of failed endoscopic retrograde cholangiopancreatography (ERCP) in children and the remedial treatment strategies.Methods:This retrospective cohort study analyzed the clinical data of 21 children who experienced failed ERCP at Beijing Children′s Hospital, Capital Medical University between January 2021 and December 2024. Data was collected included demographic information, clinical diagnoses, and ERCP outcomes. The annually trend in the ERCP failure rate was analyzed. Patients were categorized by etiology into the following groups: chronic pancreatitis, post-surgical status, pancreatic trauma, pancreas divisum, non-neoplastic pancreatic lesions, and ulcerative colitis. The relationship between etiologies and ERCP failure was analyzed by Fisher exact test.Results:A total of 175 ERCP procedures were included, of which 21 procedures failed (12.0%). The failure rate decreased annually from 2021 to 2024: 18.2% (4/22), 13.2% (5/38), 11.4% (5/44), and 9.9% (7/71), respectively. The etiological distribution among the 21 failed cases was as follows: chronic pancreatitis 28.6% (6/21), pancreatic duct stenosis following pancreatic trauma 23.8% (5/21), post-surgical status 14.3% (3/21), pancreas divisum 9.5% (2/21), acute pancreatitis 9.5% (2/21), non-neoplastic pancreatic lesions 9.5% (2/21), and pancreatic duct stenosis associated with ulcerative colitis 4.8% (1/21). Remedial treatments included surgical intervention (2 cases), ultrasound-guided percutaneous drainage (3 cases), and repeat ERCP (2 cases). For post-surgical and pancreatic trauma patients, failure was primarily due to bile duct stenosis, pancreatic duct stenosis, or pancreaticobiliary duct disruption. Active surgical interventions such as cholangiojejunostomy and pancreaticojejunostomy, and ultrasound-guided drainage following ERCP failure led to significant clinical improvement.Conclusions:A stratified management approach guided by etiology is essential following failed ERCP in children. Early and active remedial treatment, particularly surgical interventions, is recommended for post-surgical and pancreatic trauma cases.

Objective:To investigate the main causes of failed endoscopic retrograde cholangiopancreatography (ERCP) in children and the remedial treatment strategies.Methods:This retrospective cohort study analyzed the clinical data of 21 children who experienced failed ERCP at Beijing Children′s Hospital, Capital Medical University between January 2021 and December 2024. Data was collected included demographic information, clinical diagnoses, and ERCP outcomes. The annually trend in the ERCP failure rate was analyzed. Patients were categorized by etiology into the following groups: chronic pancreatitis, post-surgical status, pancreatic trauma, pancreas divisum, non-neoplastic pancreatic lesions, and ulcerative colitis. The relationship between etiologies and ERCP failure was analyzed by Fisher exact test.Results:A total of 175 ERCP procedures were included, of which 21 procedures failed (12.0%). The failure rate decreased annually from 2021 to 2024: 18.2% (4/22), 13.2% (5/38), 11.4% (5/44), and 9.9% (7/71), respectively. The etiological distribution among the 21 failed cases was as follows: chronic pancreatitis 28.6% (6/21), pancreatic duct stenosis following pancreatic trauma 23.8% (5/21), post-surgical status 14.3% (3/21), pancreas divisum 9.5% (2/21), acute pancreatitis 9.5% (2/21), non-neoplastic pancreatic lesions 9.5% (2/21), and pancreatic duct stenosis associated with ulcerative colitis 4.8% (1/21). Remedial treatments included surgical intervention (2 cases), ultrasound-guided percutaneous drainage (3 cases), and repeat ERCP (2 cases). For post-surgical and pancreatic trauma patients, failure was primarily due to bile duct stenosis, pancreatic duct stenosis, or pancreaticobiliary duct disruption. Active surgical interventions such as cholangiojejunostomy and pancreaticojejunostomy, and ultrasound-guided drainage following ERCP failure led to significant clinical improvement.Conclusions:A stratified management approach guided by etiology is essential following failed ERCP in children. Early and active remedial treatment, particularly surgical interventions, is recommended for post-surgical and pancreatic trauma cases.

Glycogen synthase 1 (GYS1) is the rate-limiting enzyme responsible for glycogen synthesis in skeletal muscle, heart, brain, and other extrahepatic tissues, playing a central role in systemic energy homeostasis. The human GYS1 gene maps to chromosome 19q13.33, comprises 16 exons, and encodes a 737-amino-acid polypeptide that is highly conserved across mammals. GYS1 activity is subject to multilayered and precisely coordinated regulation. At the transcriptional level, the GYS1 promoter contains a hypoxia response element (HRE) that mediates HIF-1α-dependent induction under low-oxygen conditions, as well as a muscle-specific enhancer harboring MEF2 and MyoD binding sites that confers tissue-restricted expression. At the post-translational level, a hierarchical phosphorylation cascade serves as the primary activity switch: glycogen synthase kinase 3β (GSK3β) sequentially phosphorylates four C-terminal serine residues following casein kinase II priming, while protein kinase A (PKA) and AMP-activated protein kinase (AMPK) provide parallel inhibitory inputs at both N- and C-terminal sites. Dephosphorylation and reactivation are mediated by protein phosphatase 1 (PP1) through tissue-specific glycogen-targeting regulatory subunits such as PPP1R3A and PPP1R3B, which anchor PP1 to glycogen particles and direct its activity toward GYS1. The allosteric activator glucose-6-phosphate (G6P) binds at the dimer interface, simultaneously enhancing catalytic efficiency and promoting dephosphorylation susceptibility, thereby establishing a feed-forward activation loop that couples substrate availability to glycogen synthesis. Beyond phosphorylation, GYS1 is regulated by ubiquitination (mediated by the E3 ligase PJA1), acetylation, O-linked β-N-acetylglucosamine (O-GlcNAc) modification, and SUMOylation, which collectively modulate protein stability, subcellular localization, and protein-protein interactions. Epigenetic mechanisms, including CpG island methylation and histone acetylation dynamics, govern chromatin accessibility at the GYS1 locus, while muscle-specific microRNAs such as miR-1 and miR-206 fine-tune GYS1 expression at the post-transcriptional level. Dysregulation of GYS1 has been identified as a central pathogenic driver in a spectrum of human diseases. In inherited glycogen storage disorders—including Lafora disease, adult polyglucosan body disease (APBD), and Pompe disease—loss of upstream regulatory control leads to GYS1 hyperactivation and the accumulation of structurally abnormal or excessive glycogen, resulting in progressive neurodegeneration, myopathy, and multiorgan dysfunction. In type 2 diabetes mellitus (T2DM), impaired insulin signaling through the PI3K-AKT-GSK3β axis maintains GYS1 in a hyperphosphorylated inactive state in skeletal muscle, compromising postprandial glucose disposal and exacerbating hyperglycemia. In oncology, GYS1 exhibits context-dependent roles across multiple cancer types. In hepatocellular carcinoma, FMO2⁺ cancer-associated fibroblasts stabilize GYS1 by competitively inhibiting PJA1-mediated ubiquitination, and stabilized GYS1 subsequently activates NF‑κB/CCL19 signaling to promote tertiary lymphoid structure formation and enhance anti-PD-1 immunotherapy responsiveness. In clear cell renal cell carcinoma, GYS1 promotes tumor progression through non-canonical NF‑κB pathway activation via the scaffold protein RPS27A. In triple-negative breast cancer, GYS1 has been identified as a trigger of disulfidptosis and an activator of NF-κB signaling through non-enzymatic facilitation of IκBα degradation. In colorectal cancer, mitochondrial fission deficiency drives AMPK-dependent GYS1 upregulation and glycogen accumulation as a compensatory survival mechanism, while in cervical cancer, GYS1-maintained glycogen reserves fuel the pentose phosphate pathway to generate NADPH for ROS clearance, thereby conferring cisplatin resistance in cancer stem cells. Therapeutic strategies targeting GYS1 have gained substantial momentum across these disease contexts. For glycogen storage disorders, antisense oligonucleotides, small interfering RNAs (e.g., ABX1100), and small-molecule inhibitors (e.g., MZ-101) have demonstrated preclinical and early clinical efficacy in reducing pathological glycogen accumulation. For T2DM, pharmacological activation of GYS1 through GSK3β inhibition or enhancement of PP1-mediated dephosphorylation is being explored to restore insulin-stimulated glycogen synthesis. In cancer, GYS1-directed interventions—including targeted silencing to sensitize tumors to chemotherapy and immune microenvironment modulation to enhance immunotherapy—represent emerging precision oncology approaches. This review provides a comprehensive and integrated account of GYS1 gene structure, tissue-specific distribution, regulatory networks, and pathogenic roles in metabolic disorders and malignancies, with the aim of establishing a theoretical framework for the development of GYS1-targeted precision therapies.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Human self-organizing cardioids, a recent breakthrough in cardiac organoid research, are constructed with the specialized cardiac lineage cells derived from human pluripotent stem cells (hPSCs) and have made rapid advancements since 2021. A key advantage of these organoids is their minimal reliance on external interventions, allowing them to more accurately replicate the heart's developmental processes through intrinsic signaling pathways, thereby closely mimicking natural cardiac characteristics. Consequently, they hold significant promise for improving drug safety evaluations, treating both congenital and acquired heart diseases, advancing eugenics practices, developing humanized cardiac disease models, conducting research in regenerative medicine, and understanding how unique environments (such as aerospace) affect human health. This review systematically describes the current various self-organizing cardioid construction techniques, comparing the structural differences caused by diverse signal stimulations, which would be instrumental in optimizing designs for more advanced and mature cardioids. Additionally, we summarize existing applications and address the challenges faced. Despite some uncertainties and challenges in current technologies and applications, this emerging cardiac organoid technology holds promise to provide new possibilities for cardiovascular medicine through continuous refinement.

BACKGROUND: Lung cancer is currently the most prevalent malignancy and the leading cause of cancer deaths worldwide. Although the early stage non-small cell lung cancer (NSCLC) presents a relatively good prognosis, a considerable number of lung cancer cases are still detected and diagnosed at locally advanced or late stages. Surgical treatment combined with perioperative multimodality treatment is the mainstay of treatment for locally advanced NSCLC and has been shown to improve patient survival. Following the standard methods of neoadjuvant therapy, perioperative management, postoperative adjuvant therapy, and other therapeutic strategies are important for improving patients' prognosis and quality of life. However, controversies remain over the perioperative management of NSCLC and presently consensus and standardized guidelines are lacking for addressing critical clinical issues in multimodality treatment. METHODS: The working group consisted of 125 multidisciplinary experts from thoracic surgery, medical oncology, radiotherapy, epidemiology, and psychology. This guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The clinical questions were collected and selected based on preliminary open-ended questionnaires and subsequent discussions during the Guideline Working Group meetings. PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) were searched for available evidence. The GRADE system was used to evaluate the quality of evidence and grade the strengths of recommendations. Finally, the recommendations were developed through a structured consensus-building process. RESULTS: The Guideline Development Group initially collected a total of 62 important clinical questions. After a series of consensus-building conferences, 24 clinical questions were identified and corresponding recommendations were ultimately developed, focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assement, and follow-up protocols for NSCLC. CONCLUSIONS This guideline puts forward reasonable recommendations focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assessment, and follow-up protocol of NSCLC. It standardizes perioperative multimodality treatment and provides guidance for clinical practice among thoracic surgeons, medical oncologists, and radiotherapists, aiming to reduce postoperative recurrence, improve patient survival, accelerate recovery, and minimize postoperative complications such as atelectasis.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/therapy* ; Combined Modality Therapy ; Perioperative Care

Objective To introduce an innovative technique, the "balance-shaped sternal elevation device" and its application in the subxiphoid uniportal video-assisted thoracoscopic surgery (VATS) for anterior mediastinal masses resection. Methods Patients who underwent single-port thoracoscopic assisted anterior mediastinal tumor resection through the xiphoid process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from May to June 2024 were included, and their clinical data were analyzed. Results A total of 7 patients were included, with 3 males and 4 females, aged 28-72 years. The diameter of the tumor was 1.9-17.0 cm. The operation time was 62-308 min, intraoperative blood loss was 5-100 mL, postoperative chest drainage tube retention time was 0-9 days, pain score on the 7th day after surgery was 0-2 points, and postoperative hospital stay was 3-12 days. All patients underwent successful and complete resection of the masses and thymus, with favorable postoperative recovery. Conclusion The "balance-shaped sternal elevation device" effectively expands the retrosternal space, providing surgeons with satisfactory surgical views and operating space. This technique significantly enhances the efficacy and safety of minimally invasive surgery for anterior mediastinal masses, reduces trauma and postoperative pain, and accelerates patient recovery, demonstrating important clinical significance and application value.

This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals ; Dermatitis, Atopic/immunology* ; Disease Models, Animal ; Mice ; Male ; Gas Chromatography-Mass Spectrometry ; Humans ; Bufonidae ; Oils/administration & dosage* ; Chromatography, High Pressure Liquid ; Female ; Mice, Inbred BALB C