Role of peritumoral tissue analysis in predicting characteristics of hepatocellular carcinoma using ultrasound-based radiomics.

Predicting the biological characteristics of hepatocellular carcinoma (HCC) is essential for personalized treatment. This study explored the role of ultrasound-based radiomics of peritumoral tissues for predicting HCC features, focusing on differentiation, cytokeratin 7 (CK7) and Ki67 expression, and p53 mutation status. A cohort of 153 patients with HCC underwent ultrasound examinations and radiomics features were extracted from peritumoral tissues. Subgroups were formed based on HCC characteristics. Predictive modeling was carried out using the XGBOOST algorithm in the differentiation subgroup, logistic regression in the CK7 and Ki67 expression subgroups, and support vector machine learning in the p53 mutation status subgroups. The predictive models demonstrated robust performance, with areas under the curves of 0.815 (0.683-0.948) in the differentiation subgroup, 0.922 (0.785-1) in the CK7 subgroup, 0.762 (0.618-0.906) in the Ki67 subgroup, and 0.849 (0.667-1) in the p53 mutation status subgroup. Confusion matrices and waterfall plots highlighted the good performance of the models. Comprehensive evaluation was carried out using SHapley Additive exPlanations plots, which revealed notable contributions from wavelet filter features. This study highlights the potential of ultrasound-based radiomics, specifically the importance of peritumoral tissue analysis, for predicting HCC characteristics. The results warrant further validation of peritumoral tissue radiomics in larger, multicenter studies.

A multicenter clinical AI system study for detection and diagnosis of focal liver lesions.

Early and accurate diagnosis of focal liver lesions is crucial for effective treatment and prognosis. We developed and validated a fully automated diagnostic system named Liver Artificial Intelligence Diagnosis System (LiAIDS) based on a diverse sample of 12,610 patients from 18 hospitals, both retrospectively and prospectively. In this study, LiAIDS achieved an F1-score of 0.940 for benign and 0.692 for malignant lesions, outperforming junior radiologists (benign: 0.830-0.890, malignant: 0.230-0.360) and being on par with senior radiologists (benign: 0.920-0.950, malignant: 0.550-0.650). Furthermore, with the assistance of LiAIDS, the diagnostic accuracy of all radiologists improved. For benign and malignant lesions, junior radiologists' F1-scores improved to 0.936-0.946 and 0.667-0.680 respectively, while seniors improved to 0.950-0.961 and 0.679-0.753. Additionally, in a triage study of 13,192 consecutive patients, LiAIDS automatically classified 76.46% of patients as low risk with a high NPV of 99.0%. The evidence suggests that LiAIDS can serve as a routine diagnostic tool and enhance the diagnostic capabilities of radiologists for liver lesions.

Primary hepatic mucosa-associated lymphoid tissue lymphoma complicated with atrial fibrillation: A case report and literature review.

RATIONALE: Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is a rare malignant primary hepatic lymphoma. The sensible choice of treatment for patients with primary lymphoma combined with atrial fibrillation (AF) is controversial and challenging. PATIENT CONCERNS: The patient presented with both primary hepatic MALT lymphoma and AF, which was difficult to manage. DIAGNOSES: Pathological and immunohistochemical examination are helpful for definitive diagnosis. INTERVENTIONS: Surgical resection and subsequent anticoagulant therapy are main treatment methods, and adjuvant therapy depends on the situation. OUTCOMES: Primary hepatic MALT lymphoma is easy to misdiagnosis due to a lack of typical symptoms and imaging signs. LESSONS: This case highlights for patients with primary hepatic MALT lymphoma combined with AF, toxicity caused by adjuvant chemotherapy should be fully considered, and careful selection should be made based on the general conditions and complications of patients.

The relationship between sex hormone-binding protein and non-alcoholic fatty liver disease using Mendelian randomisation.

BACKGROUND: The incidence of non-alcohol fatty liver disease (NAFLD) has been increasing annually with the improvement of living standards. Numerous epidemiological observations have linked sex hormone-binding protein (SHBG) levels to NAFLD. However, evidence of the causal role of SHBG in the development and progression of NAFLD is still absent. Therefore, a systematic assessment of the causal relationship is needed. METHOD: A two-sample Mendelian randomisation (MR) analysis was conducted. Genome-wide association study (GWAS) data for SHBG were obtained online from the IEU database (ebi-a-GCST90012111) as exposure. GWAS data from the NAFLD of the Finngen consortium were used for preliminary analysis, while NAFLD data from another GWAS involving 8434 participants were used for replication and meta-analyses. Causal effects were investigated with inverse variance weighted (IVW), weighted median and MR-Egger regression. Sensitivity analyses including Cochran's Q test, leave-one-out analysis and MR-Egger intercept analysis were simultaneously conducted to assess heterogeneity and pleiotropy. RESULTS: After rigorous selection, 179 single-nucleotide polymorphisms (SNPs) were identified as strongly correlated instrumental variables. Preliminary analysis suggested a significant causal relationship between genetically determined serum SHBG levels and NAFLD [odds ratio (OR) IVW = .54, 95% confidence interval (CI) = .30-.98, p = .043], supported by the results of the replication analysis (ORIVW = .61, 95% CI = .46-.81, p = .0006) and further meta-analysis (OR = .59, 95% CI = .46-.77, p < .0001). CONCLUSION: The genetic tendency to high levels of SHBG was causally correlated with a reduced risk of NAFLD, indicating that circulating high levels of SHBG was a protective factor for NAFLD.

LncRNA34977 promotes the proliferation, migration, and invasion and inhibits the apoptosis of canine mammary tumors by regulating the expression of miR-8881/ELAVL4.

Long-stranded noncoding RNAs (lncRNAs) play different roles in various diseases. lncRNA34977 has been shown to play a relevant role the development of canine mammary tumors (CMTs). However, the mechanism of lncRNA34977 in canine mammary tumors has not been fully investigated. The aim of this study was to investigate the effects of lncRNA34977 on the proliferation, migration, invasion, and apoptosis of canine mammary tumor (CMT) cells through the regulation of miR-8881/ELAVL4 expression. The apoptosis was detected by an in situ fluorescence assay and flow cytometry. The expression levels were analyzed by RT-qPCR. CCK-8, colony formation, wound healing, and Transwell assays were used to assess the proliferation, migration, and invasion. The expression of protein was detected by western blot. The siRNA-induced silencing of lncRNA34977 promoted the apoptosis of CHMp cells, and in overexpression of lncRNA34977, the result is the opposite. LncRNA34977 has a direct targeting relationship with miR-8881 and that miR-8881 is correlated with ELAVL4. Transfection of miR-8881 mimics inhibited the proliferation, migration, invasion, and promoted the apoptosis of CHMp cells of CHMp cells. In the transfection with miR-8881 inhibitors, the result is the opposite. Co-transfected with lncRNA34977, miR-8881, or ELAVL4, we found that lncRNA34977 could regulate the expression of miR-8881 or ELAVL4. Our study shows that lncRNA34977 promotes the proliferation, migration, and invasion and suppresses the apoptosis of CMT cells by regulating the expression of miR-8881/ELAVL4.

Topically applied bacteriophage to control multi-drug resistant Pseudomonas aeruginosa-infected wounds in a New Zealand rabbit model.

Pseudomonas aeruginosa (P. aeruginosa) is a widespread, gram-negative, pathogenic bacterium that causes serious internal and external infections in humans and other animals. The increasing antibiotic resistance has complicated bacterial infection treatment, and current antibiotic therapies cannot cure all infections. Owing to this, bacteriophages (phages) have regained attention as potential therapeutics for bacterial infections. In this study, the phage "PaVOA" was isolated from hospital sewage and characterized. Next, a New Zealand rabbit skin infection model was used to determine the therapeutic efficacy of PaVOA as compared to a phage cocktail or the cephalosporin antibiotic ceftriaxone. Characterization results demonstrated that phage PaVOA belongs to the Myoviridae family, has a double-stranded DNA genome, is resistant to low temperatures (-20°C), is most optimal at 40°C, has good acid-base tolerance, and remains stable for 30 min under 20 W ultraviolet (UV) intensity. The optimal multiplicity of infection of PaVOA was 0.1, and a one-step growth curve showed a short latency period (10 min), thus demonstrating its ability to rapidly kill bacteria. Furthermore, the addition of calcium (Ca) and magnesium (Mg) ions significantly increased the PaVOA titer. An in vivo phage kinetic curve showed that PaVOA was rapidly inactivated within the blood of New Zealand rabbits (undetectable after 12 h), and no animals died due to phage treatment. Wound healing studies showed that the phage cocktail induced a high healing rate and an acceleration of the skin remodeling process, and was more efficacious than ceftriaxone. Therefore, phage cocktail therapy represents a novel therapeutic approach in the treatment of traumatic skin infections caused by multi-drug resistant P. aeruginosa.

Clinical and pathological features of undifferentiated pancreatic carcinoma with osteoclastic giant cells

Introduction: undifferentiated pancreatic carcinoma with osteoclastic giant cells (UOC) is a rare pancreatic malignancy composed of three unique cell types. Currently, the histopathologic origin of UOCs remains unclear. Some studies considered that it was differentiated from epithelial tissues, while others favored a mesenchymal derivation.Methods: we present the case of a 59-year-old UOC patient with a tumor (3.0 cm × 3.0 cm × 2.5 cm) in the pancreatic neck. He underwent an en bloc resection of the distal pancreas associated with the spleen.Results: light microscopic examination revealed two typical types of UOC cells, with one type absent. The immunohistochemical staining was positive for pancytokeratin, epithelial membrane antigen, vimentin and cluster of differentiation 68, which indicated different derivations for these two kinds of cells.Discussion: UOC is a rare condition with unique imaging and pathological features. Endoscopic ultrasonography and fine needle aspiration are dispensable preoperatively. Radical resection should be tried for UOC treatments. In our opinion, osteoclastic giant cells are reactive cells derived from histocytes. The case presented here will be of interest to the whole UOC cohort. (AU)

Confusing delayed hematemesis, unusual arterial hemorrhage after pancreaticoduodenectomy: a case report.

Pancreaticoduodenectomy (PD) is one of the most complex surgeries and is associated with a high rate of complications, including bleeding, delayed gastric emptying (DGE), and pancreatic fistula. Although the frequency of postoperative hemorrhage is not high, this complication results in severe adverse outcomes. A 67-year-old man was diagnosed with pancreatic cancer and underwent PD. On the tenth day after surgery, he developed hypovolemic shock with hematemesis. Urgent digital subtraction angiography identified the bleeding artery as the jejunal mesenteric artery at the afferent loop, and the bleeding artery was embolized with two coils. After digital subtraction angiography, the patient had an uneventful recovery with no further complications. Therefore, we concluded that it is possible that bleeding may occur in the afferent loop when hemorrhage occurs after PD.

CircRNA Expression Profiles in Canine Mammary Tumours.

Numerous studies have shown that the occurrence and development of tumours are associated with the expression of circular RNAs (circRNAs). However, the expression profile and clinical significance of circRNAs in canine mammary tumours remain unclear. In this paper, we collected tissue samples from three dogs with canine mammary tumours and analysed the expression profiles of circRNAs in these samples using high-throughput sequencing technology. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses revealed 14 biological processes associated with these genes, and 11 of these genes were selected for qRT-PCR to verify their authenticity. CircRNAs have sponge adsorption to miRNAs, so we constructed a circRNA-miRNA network map using Cytoscape software. As a result, we identified a total of 14,851 circRNAs in canine mammary tumours and its adjacent normal tissues. Of these, 106 were differentially expressed (fold change ≥ 2, p ≤ 0.05), and 64 were upregulated and 42 were downregulated. The GO analysis revealed that the biological processes involved were mainly in the regulation of the secretory pathway, the regulation of neurotransmitter secretion and the positive regulation of phagocytosis. Most of these biological pathways were associated with the cGMP-PKG (cyclic guanosine monophosphate) signalling pathway, the cAMP (cyclic adenosine monophosphate) signalling pathway and the oxytocin signalling pathway. After screening, source genes closely associated with canine mammary tumours were found to include RYR2, PDE4D, ROCK2, CREB3L2 and UBA3, and associated circRNAs included chr27:26618544-26687235-, chr26:8194880-8201833+ and chr17:7960861-7967766-. In conclusion, we reveals the expression profile of circRNAs in canine mammary tumours. In addition, some circRNAs might be used as potential biomarkers for molecular diagnosis.

Fangchinoline induces gallbladder cancer cell apoptosis by suppressing PI3K/Akt/XIAP axis.

Gallbladder cancer (GBC) is the most common biliary tract malignancy with a dismal prognosis. The development of new drugs may help to improve prognosis. This study found that fangchinoline, a bisbenzylisoquinoline alkaloids, inhibited the proliferation and clone formation of GBC cells in a dose-dependent manner. Moreover, Hoechst staining, TUNEL assays, and flow cytometry demonstrated that fangchinoline effectively induced apoptosis in GBC cells. Further studies found that an anti-apoptotic pathway, the PI3K/Akt/XIAP axis, was significantly inhibited in GBC cells after treating with fangchinoline. Finally, we confirmed that fangchinoline restrained xenograft tumor growth in vivo. Our findings indicate that fangchinoline can be considered a potential drug for GBC treatment.

LncRNA Expression Profiles in Canine Mammary Tumors Identify lnc34977 as a Promoter of Proliferation, Migration and Invasion of Canine Mammary Tumor Cells.

Canine mammary tumor (CMT) is the most common tumor in canines after skin tumors. Long noncoding RNAs (lncRNAs) have crucial roles in human breast tumor initiation and progression, but the role of lncRNAs in canine mammary tumors is unclear. We analyzed the expression profiles of canine mammary tumors and their adjacent non-neoplastic tissue to explore abnormally expressed lncRNAs. LncRNA expression was detected by qRT-PCR. After overexpression of lnc40589 and knockdown of lnc34977 in CMT cells, CCK-8, colony formation, wound healing and Transwell assays were used to assess the proliferation, migration and invasive ability of canine mammary tumor cells. We also established a mammary tumor-bearing nude mouse model. GO analysis and KEGG pathway analysis demonstrated that the differentially expressed lncRNAs were closely related to the mammary tumor. lnc40589 was significantly upregulated and lnc34977 was significantly downregulated in CMTs. In addition, lnc40589 inhibits cell proliferation, migration and invasion, while lnc34977 promotes cell proliferation, migration and invasion. In addition, lnc34977 promotes the development of mammary tumors in animals. Taken together, our study results reveal the lncRNA expression profiles in CMTs and indicate that lnc34977 promotes the development of CMT both in cell culture and in vivo.

Clinical and pathological features of undifferentiated pancreatic carcinoma with osteoclastic giant cells: a rare case.

INTRODUCTION: undifferentiated pancreatic carcinoma with osteoclastic giant cells (UOC) is a rare pancreatic malignancy composed of three unique cell types. Currently, the histopathologic origin of UOCs remains unclear. Some studies considered that it was differentiated from epithelial tissues, while others favored a mesenchymal derivation. METHODS: we present the case of a 59-year-old UOC patient with a tumor (3.0 cm × 3.0 cm × 2.5 cm) in the pancreatic neck. He underwent an en bloc resection of the distal pancreas associated with the spleen. RESULTS: light microscopic examination revealed two typical types of UOC cells, with one type absent. The immunohistochemical staining was positive for pancytokeratin, epithelial membrane antigen, vimentin and cluster of differentiation 68, which indicated different derivations for these two kinds of cells. DISCUSSION: UOC is a rare condition with unique imaging and pathological features. Endoscopic ultrasonography and fine needle aspiration are dispensable preoperatively. Radical resection should be tried for UOC treatments. In our opinion, osteoclastic giant cells are reactive cells derived from histocytes. The case presented here will be of interest to the whole UOC cohort.

Huge mucinous cystic neoplasms with adhesion to the left colon: A case report and literature review.

Mucinous cystic neoplasms (MCN) are rare premalignant neoplasms of the pancreas typically found as single lesions in the pancreatic body and tail of women in the fifth and sixth decade of life, constituting 2-5% of pancreatic neoplasms. We present a 50-year-old female patient with a large tail mass of the pancreatic body (size of 15 cm × 12 cm) with elevated tumor indicators. Computed tomography and magnetic resonance imaging revealed a large cystic lesion with septa and wall nodules. During the operation, the tumor capsule wall adhered to the left half colon and mesentery and could not be detached. Splenectomy and left hemicolectomy were performed. The postoperative pathological examination of the specimens confirmed a premalignant pancreatic mucous cystic tumor with moderate heterocytosis. The preoperative diagnosis of pancreatic MCN and MCN with invasive carcinoma is discussed, considering the characteristics of this case. Age, tumor size, texture, tumor marker elevation, and cystic wall condition are important characteristics of malignant MCN. Nevertheless, it is still very difficult to determine accurately whether an MCN is malignant or not before an actual pathological examination of the resected specimen.

Intrahepatic Cholangiocarcinoma Cells Promote Epithelial-mesenchymal Transition of Hepatocellular Carcinoma Cells by Secreting LAMC2.

Hepatocellular carcinoma and intrahepatic cholangiocarcinoma cells are common primary hepatic tumor cells in the liver. Combined hepatocellular cholangiocarcinoma (CHC) contains both hepatocellular carcinoma cells and intrahepatic cholangiocarcinoma cells in one tumor lesion and these tumors show poor prognosis. Here we examined the potential interaction between hepatocellular carcinoma cells and intrahepatic cholangiocarcinoma cells using cell culture studies. The results showed that culture supernatant from intrahepatic cholangiocarcinoma cells induced endothelial-mesenchymal transition and facilitated the migration and invasion of hepatocellular carcinoma cells, although it did not accelerate the proliferation of hepatocellular carcinoma cells. Furthermore, culture supernatant from intrahepatic cholangiocarcinoma cells increased the chemoresistance of hepatocellular carcinoma cells. Laminin subunit gamma 2 (LAMC2) was detected in the culture supernatant of intrahepatic cholangiocarcinoma cells but not in that of hepatocellular carcinoma cells. Using established LAMC2 knockout intrahepatic cholangiocarcinoma cells, our results demonstrated that intrahepatic cholangiocarcinoma cells promoted the epithelial-mesenchymal transition of hepatocellular carcinoma cells through secreting LAMC2. Our results have revealed a novel mechanism of interaction between intrahepatic cholangiocarcinoma cells and hepatocellular carcinoma cells, which may provide new insight into developing effective treatments for CHC.

Pterostilbene inhibits gallbladder cancer progression by suppressing the PI3K/Akt pathway.

Gallbladder cancer is the most common malignant tumor of the biliary system and is characterized by difficulty to diagnose in early stages, a high degree of malignancy, and poor prognosis. Finding new drugs may improve the prognosis for this dismal cancer. Herein, we investigated the potential application of pterostilbene (PTS) against gallbladder cancer in vivo and in vitro. PTS potently inhibited cell proliferation, migration and invasion of gallbladder cancer cells. Moreover, PTS also had a function of inducing apoptosis in vitro. Meanwhile, PTS reversed EMT with a correlated inhibition of PI3K/Akt activation. Tumor xenograft models showed that PTS inhibited tumor growth and had low toxicity in vivo, which were consistent with the in vitro data. These findings indicate that PTS arrests cell growth through inhibition of PI3K/AKT signaling and is a potential drug for the therapy of gallbladder cancer.

Inhibition of heat shock protein 90 alleviates cholestatic liver injury by decreasing IL-1ß and IL-18 expression.

Severe cholestatic liver injury diseases, such as obstructive jaundice and the subsequent acute obstructive cholangitis, are induced by biliary tract occlusion. Heat shock protein 90 (HSP90) inhibitors have been demonstrated to be protective for various organs. The potential of HSP90 inhibitors in the treatment of cholestatic liver injury, however, remains unclear. In the present study, rat models of bile duct ligation (BDL) were established, the HSP90 inhibitor 17-dimethylamino-ethylamino-17-demethoxygeldanamycin (17-DMAG) was administered, and its ability to ameliorate the cholestasis-induced liver injuries was evaluated. In the BDL rat models and clinical samples, increased HSP90 expression was observed to be associated with cholestatic liver injury. Furthermore, 17-DMAG alleviated cholestasis-induced liver injury in the rat models, as revealed by the assessment of pathological changes and liver function. In addition, 17-DMAG protected hepatocytes against cholestatic injury in vitro. Further assays indicated that 17-DMAG administration prevented cholestasis-induced liver injury in the rats by decreasing the expression of interleukin (IL)-1ß and IL-18. Moreover, 17-DMAG also decreased the cholestasis-induced upregulation of IL-1ß and IL-18 in liver sinusoidal endothelial cells in vitro. In conclusion, the HSP90 inhibitor 17-DMAG is able to prevent liver injury in rats with biliary obstruction, and this phenomenon is associated with the reduction of IL-1ß and IL-18 expression.

Development and multicenter validation of a nomogram for preoperative prediction of lymph node positivity in pancreatic cancer (NeoPangram).

BACKGROUND: Neoadjuvant therapy is associated with nodal downstaging and improved oncological outcomes in patients with lymph node (LN)-positive pancreatic cancer. This study aimed to develop and validate a nomogram to preoperatively predict LN-positive disease. METHODS: A total of 558 patients with resected pancreatic cancer were randomly and equally divided into development and internal validation cohorts. Multivariate logistic regression analysis was used to construct the nomogram. Model performance was evaluated by discrimination, calibration, and clinical usefulness. An independent multicenter cohort consisting of 250 patients was used for external validation. RESULTS: A four-marker signature was built consisting of carbohydrate antigen 19-9 (CA19-9), CA125, CA50, and CA242. A nomogram was constructed to predict LN metastasis using three predictors identified by multivariate analysis: risk score of the four-marker signature, computed tomography-reported LN status, and clinical tumor stage. The prediction model exhibited good discrimination ability, with C-indexes of 0.806, 0.742 and 0.763 for the development, internal validation, and external validation cohorts, respectively. The model also showed good calibration and clinical usefulness. A cut-off value (0.72) for the probability of LN metastasis was determined to separate low-risk and high-risk patients. Kaplan-Meier survival analysis revealed a good agreement of the survival curves between the nomogram-predicted status and the true LN status. CONCLUSIONS: This nomogram enables the identification of pancreatic cancer patients at high risk for LN positivity who may have more advanced disease and thus could potentially benefit from neoadjuvant therapy.