Imaging Evaluation of Liver Tumors in Pediatric Patients

Imaging plays crucial roles in the management of pediatric patients with suspected liver malignant tumors. Three-dimensional (3D) imaging could significantly improve the resection rate of pediatric tumors and increase the safety of the surgery. With the development of medical imaging, 3D reconstruction technology, the innovation of liver surgery and the proposal of precise hepatectomy, the intrahepatic vascular anatomy of the liver and liver segmentectomy based on that vascular anatomy have become well developed. With the analysis of 3D digital liver, we proposed a new type of liver classification system: Dong’s digital liver classification system. And we measured the normal total liver volume from neonate to aging making a reference for surgeons all around the world. And the Human Digital Liver Database was established by the Affiliated Hospital of Qingdao University and Hisense Company, aiming to collect digital liver from neonates, children, adults, and the elderly, from normal livers, livers with cancer, and simulated livers resected using Hisense CAS. Then we showed one case report of patient with giant liver tumor. With the application of Hisense CAS and our data, we successfully removed the tumor. We believe that the new techniques in imaging will help surgeons to accomplish better operations

Diagnosis and Treatment of Hepatoblastoma: An Update

Hepatoblastoma is a rare but the most common solid tumor in children. The incidence is gradually increasing. The international collaboration among four centers in the world has greatly improved the prognosis of hepatoblastoma. They formed the Children’s Hepatic Tumor International Collaboration (CHIC) to standardize the staging system (2017 PRETEXT system) and the risk factors for tumor stratification. Multimodal therapy has become the standard for the management of hepatoblastoma, including surgical resection, liver transplantation, chemotherapy, and so on. Surgery is the primary treatment of early stage hepatoblastoma. Three-dimensional reconstruction is helpful for preoperative evaluation of large tumors, assisting extended hepatectomy for patients in PRETEXT III or IV. Neoadjuvant therapy is useful for reducing the tumor volume and increasing the resectability. Primary liver transplantation is recommended for advanced hepatoblastoma. The lungs are the most common metastatic organ, the treatment of which is critical for the patient’s long-term survival. We reviewed the recent progress in the diagnosis and treatment of hepatoblastoma

The TTYH3/MK5 Positive Feedback Loop regulates Tumor Progression via GSK3-β/β-catenin signaling in HCC

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and identification of novel targets is necessary for its diagnosis and treatment. This study aimed to investigate the biological function and clinical significance of tweety homolog 3 (TTYH3) in HCC. TTYH3 overexpression promoted cell proliferation, migration, and invasion and inhibited HCCM3 and Hep3B cell apoptosis. TTYH3 promoted tumor formation and metastasis in vivo. TTYH3 upregulated calcium influx and intracellular chloride concentration, thereby promoting cellular migration and regulating epithelial-mesenchymal transition-related protein expression. The interaction between TTYH3 and MK5 was identified through co-immunoprecipitation assays and protein docking. TTYH3 promoted the expression of MK5, which then activated the GSK3β/β-catenin signaling pathway. MK5 knockdown attenuated the activation of GSK3β/β-catenin signaling by TTYH3. TTYH3 expression was regulated in a positive feedback manner. In clinical HCC samples, TTYH3 was upregulated in the HCC tissues compared to nontumor tissues. Furthermore, high TTYH3 expression was significantly correlated with poor patient survival. The CpG islands were hypomethylated in the promoter region of TTYH3 in HCC tissues. In conclusion, we identified TTYH3 regulates tumor development and progression via MK5/GSK3-β/β-catenin signaling in HCC and promotes itself expression in a positive feedback loop

The Emerging Role of Bone-Derived Hormones in Diabetes Mellitus and Diabetic Kidney Disease

Diabetic kidney disease (DKD) causes the greatest proportion of end-stage renal disease (ESRD)–related mortality and has become a high concern in patients with diabetes mellitus (DM). Bone is considered an endocrine organ, playing an emerging role in regulating glucose and energy metabolism. Accumulating research has proven that bone-derived hormones are involved in glucose metabolism and the pathogenesis of DM complications, especially DKD. Furthermore, these hormones are considered to be promising predictors and prospective treatment targets for DM and DKD. In this review, we focused on bone-derived hormones, including fibroblast growth factor 23, osteocalcin, sclerostin, and lipocalin 2, and summarized their role in regulating glucose metabolism and DKD

Osteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis

Exercise results in mechanical loading of the bone and stimulates energy expenditure in the adipose tissue. It is therefore likely that the bone secretes factors to communicate with adipose tissue in response to mechanical loading. Interleukin (IL)−11 is known to be expressed in the bone, it is upregulated by mechanical loading, enhances osteogenesis and suppresses adipogenesis. Here, we show that systemic IL-11 deletion (IL-11−/−) results in reduced bone mass, suppressed bone formation response to mechanical loading, enhanced expression of Wnt inhibitors, and suppressed Wnt signaling. At the same time, the enhancement of bone resorption by mechanical unloading was unaffected. Unexpectedly, IL-11−/− mice have increased systemic adiposity and glucose intolerance. Osteoblast/osteocyte-specific IL-11 deletion in osteocalcin-Cre;IL-11fl/fl mice have reduced serum IL-11 levels, blunted bone formation under mechanical loading, and increased systemic adiposity similar to IL-11−/− mice. Adipocyte-specific IL-11 deletion in adiponectin-Cre;IL-11fl/fl did not exhibit any abnormalities. We demonstrate that osteoblast/osteocyte-derived IL-11 controls both osteogenesis and systemic adiposity in response to mechanical loading, an important insight for our understanding of osteoporosis and metabolic syndromes

ICTP as a marker for atherosclerosis

Carboxy-terminal telopeptide of type I collagen (ICTP) is generated through matrix metalloproteinase (MMP)-dependent type I collagen digestion, and has been widely utilized as a biomarker for bone turnover. The fact that atherosclerotic lesions are rich in both type I collagen and MMP-producing macrophages led to the hypothesis that serum ICTP concentrations may serve as a non-invasive clinical biomarker for atherosclerosis. Therefore, the association of serum ICTP concentrations with the maximum intima-media thickness (IMT) of carotid arteries, a surrogate index of systemic atherosclerosis, or brachial-ankle pulse wave velocity (baPWV) in patients with atherosclerotic risk factors was evaluated. A total of 52 male and 65 female (mean age: 62.8 yrs) patients without renal failure, malignancies or bone diseases known to affect serum ICTP concentrations were recruited. Patients with max IMTs ≥1.1 mm showed significantly higher serum ICTP concentrations compared with patients with max IMTs <1.1 mm (3.33 ± 0.97 vs 2.82 ± 0.65 ng/mL, p<0.05). Serum ICTP concentration was also positively correlated with max IMT (p<0.001) or baPWV values (p<0.05). Multivariate analyses also revealed that serum ICTP concentrations were correlated with max IMT (p<0.001; 95% CI 0.200 to 0.454). These results suggest that serum ICTP concentrations can be used as a non-invasive biomarker for systemic atherosclerosis

Disulfidptosis-associated long non-coding RNA signature predicts the prognosis, tumor microenvironment, and immunotherapy and chemotherapy options in colon adenocarcinoma

Abstract Background Disulfidptosis is independent of apoptosis, ferroptosis, and cuproptosis and is associated with cancer progression, treatment response, and prognosis. However, the predictive potential of disulfidptosis-associated lncRNAs in colon adenocarcinoma (COAD) and their features in the tumor immune microenvironment (TIME) require further elucidation. Methods RNA transcriptome, clinical information, and mutation data of COAD samples were obtained from the TCGA database. The risk model was first constructed by co-expression analysis of disulfidptosis genes and lncRNAs, and prognostic lncRNAs were screened using Cox regression, followed by least absolute shrinkage and selection operator analysis. Enrichment analyses were performed to explore the underlying biological functions and signaling of model-associated differentially expressed genes (MADEGs). Moreover, TIME of MADEGs was analyzed to assess the immunotherapy. Finally, the expression levels of the lncRNAs were verified by taking specimens of patients with COAD from the Affiliated Hospital of Qingdao University. Results We constructed a prognosis-related risk model based on four disulfidptosis-associated lncRNAs (ZEB1-AS1, SNHG16, SATB2-AS1, and ALMS1-IT1). By analyzing the survival of patients in the whole, training, and test groups, we found that patients with COAD in the low-risk group had better overall survival than those in the high-risk group. Validation of the model via Cox analysis and clinical indicators demonstrated that the model had a decent potential for predicting the prognosis of patients with COAD. Enrichment analyses revealed that the MADEGs were related to disulfidptosis-associated biological functions and cancer pathways. Furthermore, patients with COAD in the high-risk group had more positive responses to immune checkpoint inhibitors (ICIs) than those in the low-risk group, as confirmed by TIME analysis. ZEB1-AS1, SNHG16, and ALMS1-IT1 were expressed at higher levels in tumor samples than those in the corresponding paracancerous samples (p < 0.05), whereas SATB2-AS1 was upregulated in the paracancerous samples (p < 0.05). Conclusions This signature may guide prognosis, molecular mechanisms, and treatment strategies, including ICIs and chemotherapy, in patients with COAD

Pancreatobiliary reflux increases macrophage-secreted IL-8 and activates the PI3K/NFκB pathway to promote cholangiocarcinoma progression

Background: Persistent pancreaticobiliary reflux (PBR) is associated with a high risk of biliary malignancy. This study aimed to evaluate the proportion of PBR in biliary tract diseases and mechanisms by which PBR promoted cholangiocarcinoma progression. Methods: Overall 227 consecutive patients with primary biliary tract disease participated in this study. The amylase levels in the collected bile were analyzed. The mechanisms underlying the effect of high-amylase bile on bile duct epithelial and cholangiocarcinoma cells progression were analyzed. The source of interleukin-8 (IL-8) and its effects on the biological functions of cholangiocarcinoma cells were investigated. Results: The bile amylase levels in 148 of 227 patients were higher than the upper serum amylase limit of 135 IU/L. PBR was significantly correlated with sex, pyrexia, and serum gamma-glutamyl transferase (GGT) levels in the patient cohort. High-amylase bile-induced DNA damage and genetic differences in the transcript levels of the gallbladder mucosa and facilitated the proliferation and migration of bile duct cancer cells (HUCCT1 and QBC939 cells). The concentration of many cytokines increased in high-amylase bile. IL-8 is secreted primarily by macrophages via the mitogen-activated protein kinase pathway and partially by bile duct epithelial cells. IL-8 promotes the progression of HUCCT1 and QBC939 cells by regulating the expression of epithelial-mesenchymal transition-associated proteins and activating the phosphatidylinositol 3-kinase/nuclear factor kappa-B pathway. Conclusions: PBR is one of the primary causes of biliary disease. IL-8 secreted by macrophages or bile duct epithelial cells stimulated by high-amylase bile promotes cholangiocarcinoma progression

SPINAL GOUT: A REPORT OF THREE CASES AND LITERATURE REVIEW

Objective To investigate the features of patients with spinal gout, and to improve diagnostic accuracy among clinicians. Methods Related clinical data were collected from three patients with spinal gout who were admitted to our hospital, and a literature review was performed. Results All three patients had previously been diagnosed with gout and received surgical treatment for the symptoms of cervical or lumbar nerve involvement. Patient 1 had a normal level of serum uric acid (sUA), while patients 2 and 3 had an increase in the level of sUA. For patients 1 and 3, preoperative spinal magnetic resonance showed decreased T2WI signal, and patient 1 had a high possibility of inflammation of the cervical vertebrae C3-7, while patient 3 had circular high-density shadow and clear sclerotic edge in the cervical vertebrae C4-6. Postoperative pathological examination showed gouty granuloma in patients 1 and 2, and patient 3 was found to have chronic inflammation with hyaline change, granulomatous hyperplasia, and multinucleated giant cell reaction in fibrovascular tissue. All three patients achieved varying degrees of relief of nerve compression symptoms after surgery. Conclusion The possibility of spinal gout should be considered if patients with gout have nerve compression symptoms and the features of typical bone damage in gout found by radiological examination, and it is necessary to complete the examination of sUA and urate crystal deposition in time, confirm the diagnosis of spinal gout before surgery, and make adequate preparation before surgery