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ObjectiveThis study aimed to comprehensively investigate hypervirulent carbapenem-resistant Klebsiella pneumoniae (CR-hvKP) in the Ningbo region. Importantly, we sought to elucidate its molecular characteristics and pathogenic mechanisms. This information will provide evidence-based insights for preventing and controlling nosocomial infections and facilitate improved clinical diagnosis and treatment in this region. Methods96 carbapenem-resistant Klebsiella pneumoniae strains were collected from the Ningbo region between January 2021 and December 2022. Whole genome sequencing and bioinformatic methods were employed to identify and characterize CR-hvKP strains at the molecular level. The minimum inhibitory concentrations (MICs) of common clinical antibiotics were determined using the VITEK-2 Compact automatic microbiological analyzer. Plasmid conjugation experiments evaluated the transferability of resistance plasmids. Finally, mouse virulence assays were conducted to explore the pathogenic mechanisms.ResultsAmong the 96 strains, a single CR-hvKP strain, designated CR-hvKP57, was identified, with an isolation frequency of 1.04%. Whole-genome sequencing revealed the strain to be ST23 serotype with a K1 capsule. This strain harbored three plasmids. Plasmid 1, a pLVPK-like virulence plasmid, carried multiple virulence genes, including rmpA, rmpA2, iroB, iucA, and terB. Plasmid 2 contained transposable element sequences such as IS15 and IS26. Plasmid 3, classified as a resistance plasmid, harbored the blaKPC-3 carbapenem resistance gene. Mouse virulence assays demonstrated a high mortality rate associated with CR-hvKP57 infection. Additionally, there was a significant increase in IL-1β, IL-6, and TNF-α levels in response to CR-hvKP57 infection, indicating varying degrees of inflammatory response. Western blot experiments further suggested that the pathogenic mechanism involves activation of the NF-κB signaling pathway.ConclusionThis study confirms the emergence of hypervirulent CR-hvKP in the Ningbo region, which likely resulted from the acquisition of a pLVPK-like virulence plasmid and a blaKPC-3 resistance plasmid by the ST23-K1 type Klebsiella pneumoniae. Our findings highlight the urgent need for more judicious use of antibiotics to limit the emergence of resistance. Additionally, strengthening infection prevention and control measures is crucial to minimize the spread of virulence and resistance plasmids.

Melanoma is the deadliest skin tumor and is prone to distant metastases. The incidence of melanoma has increased rapidly in the past few decades, and current trends indicate that this growth is continuing. This study was aimed to explore the molecular mechanisms of melanoma pathogenesis and discover underlying pathways and genes associated with melanoma. We used high-throughput expression data to study differential expression profiles of related genes in melanoma. The differentially expressed genes (DEGs) of melanoma in GSE15605, GSE46517, GSE7553, and the Cancer Genome Atlas (TCGA) datasets were analyzed. Differentially expressed genes (DEGs) were identified by paired t-test. Then the DEGs were performed cluster and principal component analyses and protein–protein interaction (PPI) network construction. After that, we analyzed the differential genes through bioinformatics and got hub genes. Finally, the expression of hub genes was confirmed in the TCGA databases and collected patient tissue samples. Total 144 up-regulated DEGs and 16 down-regulated DEGs were identified. A total of 17 gene ontology analysis (GO) terms and 11 pathways were closely related to melanoma. Pathway of pathways in cancer was enriched in 8 DEGs, such as junction plakoglobin (JUP) and epidermal growth factor receptor (EGFR). In the PPI networks, 9 hub genes were obtained, such as loricrin (LOR), filaggrin (FLG), keratin 5 (KRT5), corneodesmosin (CDSN), desmoglein 1 (DSG1), desmoglein 3 (DSG3), keratin 1 (KRT1), involucrin (IVL), and EGFR. The pathway of pathways in cancer and its enriched DEGs may play important roles in the process of melanoma. The hub genes of DEGs may become promising melanoma candidate genes. Five key genes FLG, DSG1, DSG3, IVL, and EGFR were identified in the TCGA database and melanoma tissues. The results suggested that FLG, DSG1, DSG3, IVL, and EGFR might play important roles and potentially be valuable in the prognosis and treatment of melanoma. These hub genes might well have clinical significance as diagnostic markers.

Plasmacytoma variability translocation 1 (PVT1), an oncogene, has been reported to be highly expressed in many tumors, including human glioma, gastric cancer, and non-small cell lung cancer. Functionally, it could also regulate the development of tumor cells. However, its specific roles and pathogenesis in human gliomas are still not clear. This study investigated the function and mechanism of PVT1 knockdown in the proliferation and malignant transformation of human gliomas. We first examined the expression levels of PVT1 and miR- 424 in human glioma tissues and cell lines. We also used gene manipulation techniques to explore the effects of PVT1 knockdown on cell viability, migration, invasion, and miR-424. We found that PVT1 knockdown effectively inhibited cell viability, migration, and invasion of human glioma cells and increased miR-424 expression. Based on the negative correlation between PVT1 and miR-424, we then confirmed the direct interaction between PVT1 and miR-424 using RNA immunoprecipitation (RIP) and luciferase reporter assays. Further, we established a xenograft nude mouse model to determine the role and mechanism of PVT1 on tumor growth in vivo. In addition, PVT1 knockdown was shown to promote miR-424 in vivo. In summary, the present study demonstrated that PVT1 knockdown could negatively regulate miR-424 to inhibit human glioma cell activity, migration, and invasiveness. PVT1 knockdown could negatively regulate miR-424 to inhibit cellular activity, migration, and invasiveness in human gliomas, which explained the oncogenic mechanism of PVT1 in human gliomas. It also suggested that PVT1 might be a novel therapeutic target for human gliomas. [ABSTRACT FROM AUTHOR]

Abstract Increasing studies have pointed out that small nucleolar RNAs (snoRNAs) and their host genes (SNHGs) have multi-functional roles in cancer progression. Bioinformatics analysis revealed the importance of snoRNA host gene 25 (SNHG25) in neuroblastoma (NB). Hence, we further explored the function and molecular mechanism of SNHG25 in NB. Our study revealed that SNHG25 expression was upregulated in NB cells. Through loss-of-function assays, we discovered that silencing of SNHG25 suppressed NB cell proliferation, invasion, and migration. Moreover, we found that SNHG25 positively regulated snoRNA small nucleolar RNA, H/ACA box 50 C (SNORA50C) in NB cells, and SNORA50C depletion had the same function as SNHG25 silencing in NB cells. Moreover, we proved that SNHG25 recruited dyskerin pseudouridine synthase 1 (DKC1) to facilitate SNORA50C accumulation and associated small nucleolar ribonucleoprotein (snoRNP) assembly. In addition, it was manifested that SNHG25 relied on SNORA50C to inhibit ubiquitination of histone deacetylase 1 (HDAC1), thereby elevating HDAC1 expression in NB cells. Further, HDAC1 was proven to be a tumor-facilitator in NB, and SNORA50C contributed to NB cell growth and migration through the HDAC1-mediated pathway. In vivo xenograft experiments further supported that SNHG25 promoted NB progression through SNORA50C/HDAC1 pathway. Our study might provide a novel sight for NB treatment.

The objective of this study was to determine if genotypes with differing globulin subunit compositions affect the hypocholesterolemic effect (HCE) of soy protein isolates (SPIs). Six SPIs (300 mg/kg/day), which differed in the 11S/7S globulin subunit composition, and fenofibrate (FF) (30 mg/kg/day), a hypocholesterolemic drug, were administered by gavage for 28 days to hypercholesterolemic model rats (HMRs). Blood samples were collected to measure serum lipid parameters. Hepatic histopathologic and lipid biochemical data were collected, and the expression of cholesterol metabolism-related key genes was analyzed. Our results demonstrated that soybeans differing in genotype generate SPIs with marked different HCEs, and the mechanism underlying the various HCEs of SPIs is associated with differential expression of hepatic cholesterol metabolism-related key genes in HMRs. 7S(α′+α)-Null genotype provided a greater effect on increasing HDL-C level, and daily ingestion of SPI-2 (null α′, α) might significantly contribute to increase HDL-C level in HMRs.

Summary: Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children. We found that TTF1, TrkA, and miR-204 were lowly expressed, whereas TrkB was highly expressed in undifferentiated NB tissues. Meanwhile, TTF1 expression correlated positively with TrkA and miR-204 expression but negatively with TrkB expression. The TTF1 promoter was hypermethylated in undifferentiated NB tissues and SK-N-BE cells, leading to TTF1 downregulation. We also identified miR-204, which directly targets TrkB, as a transcriptional target of TTF1. Functionally, TTF1 suppressed proliferation, migration, and invasion of NB cells, whereas induced cell cycle arrest, apoptosis, and autophagy of NB cells by regulating TrkA and the miR-204-TrkB axis. Furthermore, TTF1 suppressed tumor growth and promoted neurogenic differentiation in a NB xenograft mouse model. Our study demonstrates that TTF1 reduces tumor growth and induces neurogenic differentiation in NB by directly targeting TrkA and the miR-204/TrkB axis.

Abstract Background To report the outcomes of hepatoblastoma resected in our institution. Methods We diagnosed 135 children with hepatoblastoma at our institution between January 2010 and December 2017. Patients who underwent liver resection were included for analysis. However, patients who abandoned treatment after diagnosis were excluded from analysis, but their clinical characteristics were provided in the supplementary material. Results Forty-two patients abandoned treatment, whereas 93 patients underwent liver resection and were included for statistical analysis. Thirty-six, 23, 3, and 31 patients had PRETEXT stages II, III, IV, and unspecified tumours, respectively. Seven patients had ruptured tumour; 9 had lung metastasis (one patient had portal vein thrombosis concurrently). Sixteen patients underwent primary liver resection; 22, 25, and 30 patients received cisplatin-based neoadjuvant chemotherapy and delayed surgery, preoperative transarterial chemoembolization (TACE) and delayed surgery, and a combination of cisplatin-based neoadjuvant chemotherapy, TACE, and delayed surgery, respectively. Forty patients had both PRETEXT and POST-TEXT information available for analysis. Twelve patients were down-staged after preoperative treatment, including 2, 8, and 2 patients from stages IV to III, III to II, and II to I, respectively. Ten patients with unspecified PRETEXT stage were confirmed to have POST-TEXT stages II (n = 8) and I (n = 2) tumours. Seven tumours were associated with positive surgical margins, and 12 patients had microvascular involvement. During a median follow-up period of 30.5 months, 84 patients survived without relapse, 9 experienced tumour recurrence, and 4 died. The 2-year event-free survival (EFS) and overall survival (OS) rates were 89.4 ± 3.4%, and 95.2 ± 2.4%, respectively; they were significantly better among patients without metastasis (no metastasis vs metastasis: EFS, 93.5 ± 3.7% vs 46.7 ± 19.0%, adjusted p = 0.002. OS, 97.6 ± 2.4% vs 61.0 ± 18.1%, adjusted p = 0.005), and similar among patients treated with different preoperative strategies (chemotherapy only vs TACE only vs Both: EFS, 94.7 ± 5.1% vs 91.7 ± 5.6% vs 85.6 ± 6.7%, p = 0.542. OS, 94.1 ± 5.7% vs 95.7 ± 4.3% vs 96.7 ± 3.3%, p = 0.845). Conclusion The OS for patients with hepatoblastoma who underwent liver resection was satisfactory. Neoadjuvant chemotherapy and TACE seemed to have a similar effect on OS. However, the abandonment of treatment by patients with hepatoblastoma was common, and may have biased our results.

PurposeIndocyanine green (ICG) fluorescence imaging is becoming increasingly popular in adult oncologic surgery, but remains relatively uncommon in pediatric oncologic surgery. Herein, we report our experience with the use of ICG fluorescence imaging in the resection of hepatoblastoma (HB).Patients and MethodsHepatoblastoma patients who underwent liver resection with ICG fluorescence imaging between January 2020 and March 2021 were included in this study. Patients’ demographic data, clinical information, and detailed information of the use of ICG fluorescence imaging were retrospectively reviewed.ResultsSixteen HB patients underwent ICG fluorescence imaging-guided liver resection. There were 11 males and 5 females, age ranged from 8 to 134 months. The initial alpha-fetoprotein ranged from 436 to 528,390 ng/ml. There were one pre-treatment extent of tumor stage I, nine stage II, four stage III, and two stage IV. Three patients underwent up-front hepatectomy, 13 patients received 2–8 cycles of platinum-based neoadjuvant chemotherapy and underwent delayed hepatectomy. ICG (0.5 mg/kg) was given intravenously 48–72 h prior to surgery. The operative time ranged from 180 to 400 min. All patients achieved negative surgical margins. In two patients, ICG identify additional lesions which were not detected in preoperative imaging.ConclusionICG fluorescence imaging is useful in the resection of HB and may detect small lesions not shown in preoperative imaging.

Abstract Background Hepatoblastoma is the most common hepatic malignancy in children, accounting for approximately 80% of all childhood liver tumors. KRAS and NRAS, members of the RAS gene family, are closely linked to tumorigenesis, and are frequently mutated in a variety of malignancies. They may thus play critical roles in tumorigenesis. However, there are few studies on the association between the RAS gene polymorphisms and risk of hepatoblastoma. Methods We investigated whether the polymorphisms at these genes are associated with hepatoblastoma susceptibility in a hospital-based study of 213 affected Chinese children and 958 cancer-free controls. Genotypes were determined by TaqMan assay, and association with hepatoblastoma risk was assessed based on odds ratios and 95% confidence intervals. Results No significant differences were observed between patients and controls in terms of age and gender frequency. All NRAS and KRAS genotypes are in Hardy–Weinberg equilibrium in the entire study population. We did not observe any significant association between hepatoblastoma risk and polymorphisms at NRAS and KRAS. The association between selected polymorphisms and hepatoblastoma risk was assessed after stratification by age, gender, and clinical stage. However, no significant association was observed even after stratification by age, gender, and clinical stage. Conclusions The data suggest that NRAS and KRAS polymorphisms are irrelevant to hepatoblastoma susceptibility among Chinese population.

Neuroblastoma is the most common extracranial solid tumor in childhood. However, ganglioneuroma (GN) and ganglioneuroblastoma intermixed (GNBI), are considerably rare. Herein, we reported a rare case of bilateral thoracic and adrenal GN and GNBI in a 5-year-old boy. A three-stage operation was performed and all tumors were completely resected. The patient received no further treatment and no recurrence was found during a 2-year follow-up.

An Ni-CeO2 catalyst with high Ni loading (50 wt.%) prepared by a salt-assisted solution combustion method was characterized by different methods and used for CO2 methanation. The specific surface area of the Ni-CeO2 catalyst prepared by salt-assisted solution combustion is 7 times that of the catalyst prepared by conventional solution combustion. The Ni-CeO2 catalyst prepared by salt-assisted solution combustion has smaller particle sizes of Ni and exhibits excellent activity at low temperatures. The high Ni loading and small Ni particle size can provide more metal Ni site and Ni-CeO2 interface, which help to improve the CO2 methanation performance.

Developing low-temperature nickel-based catalysts with good resistance to coking and sintering for dry reforming of methane (DRM) is of great significance. In this work, Ni (5 wt%) and CeO2 (5 wt%) were supported on SBA-15 porous material by glycine-assisted impregnation method to obtain Ni-CeO2/SBA-15-G catalyst. XRD and TEM results showed that the addition of glycine can effectively promote the dispersion of NiO and CeO2 in the pores of SBA-15. H2-TPR and XPS results confirmed the formation of stronger metal-support interaction. In addition, after the addition of glycine, the NixCe1−xOy solid solution content was increased significantly, meanwhile, the Ce3+ concentration was increased from 31% to 49%, accompanied by more oxygen vacancies and generation of active oxygen species. For the above reasons, Ni-CeO2/SBA-15-G had better catalytic performance in the low-temperature DRM test (20 h, 600 °C) with high GHSV (600,000 mL/gcat/h), its CH4 conversion after reaction of 20 h was 2 times that of Ni-CeO2/SBA-15-C catalyst prepared by a conventional impregnation method. TGA-DTA test also proved that Ni-CeO2/SBA-15-G almost completely eliminated carbon deposition. The above advantages of the Ni-CeO2/SBA-15-G catalyst may have originated from the complexation of glycine with metal cations and can prevent them from gathering.

Abstract Background The rs2147578 C > G polymorphism in the long non-coding RNA gene Lnc-LAMC2–1:1 is associated with increased susceptibility to a few types of cancers. However, its role in neuroblastoma has not been evaluated yet. Methods We investigated the association between the lnc-LAMC2–1:1 rs2147578 C > G polymorphism and neuroblastoma susceptibility in Chinese Han populations. A total of 393 neuroblastoma cases and 812 healthy individuals from the Henan and Guangdong provinces were enrolled and subjected to genotyping. Odds ratio (OR) and 95% confidence interval (CI) were used to determine the strength of the association of interest. Results Combined analysis revealed that the lnc-LAMC2–1:1 rs2147578 C > G polymorphism was associated with increased neuroblastoma susceptibility (CG vs. CC: adjusted OR = 1.33, 95% CI = 1.01–1.75, P = 0.045; CG/GG vs. CC: adjusted OR = 1.34, 95% CI = 1.03–1.74, P = 0.028). In stratification analysis, children under 18 months with rs2147578 CG/GG genotypes had an increased neuroblastoma risk (adjusted OR = 1.70, 95% CI = 1.08–2.67, P = 0.022). Females with rs2147578 CG/GG genotypes also had increased neuroblastoma susceptibility (adjusted OR = 2.08, 95% CI = 1.37–3.18, P = 0.0007). In addition, children with lnc-LAMC2–1:1 rs2147578 CG/GG genotypes were prone to develop earlier stages of neuroblastoma (adjusted OR = 1.46, 95% CI = 1.01–2.12, P = 0.046). Conclusions The Lnc-LAMC2–1:1 rs2147578 C > G polymorphism may contribute to increased neuroblastoma susceptibility in children of Henan province.

BackgroundHepatoblastoma (HB) is the most common hepatic malignancy in children, accounting for approximately 80% of all childhood liver tumors. Previous genome-wide association studies (GWASs) have found that the LINC00673 rs11655237 C>T polymorphism is associated with the risk of several different adult cancers. However, the association between this polymorphism and HB susceptibility remains unclear.MethodsWe analyzed the association between the LINC00673 rs11655237 C>T polymorphism and HB susceptibility in a hospital-based study of Chinese children. We enrolled 213 HB patients and 958 healthy controls with genotypes determined by TaqMan, and the strength of the association of interest was determined by calculating odds ratios (ORs) and 95% confidence intervals (CIs).FindingsWe found a significant association between the LINC00673 rs11655237 C>T polymorphism and HB risk (CT/TT compared with CC: adjusted OR = 1.40, 95% CI = 1.04–1.88, p = 0.029). Furthermore, stratified analysis indicated that rs11655237 T allele carriers in the following subgroups were more likely to develop HB: children older than 17 months, males, and those with tumors of clinical stages III + IV.InterpretationIn conclusion, we confirmed that the LINC00673 rs11655237 C>T polymorphism may be associated with HB susceptibility. Prospective studies with larger sample sizes and patients of different ethnicities are needed to validate our findings.

Objective To investigate the impact of using a three-dimensional (3D) printed liver model for patient education. Methods Children with hepatic tumours who were scheduled for hepatectomy were enrolled, and patient-specific 3D liver models were printed with photosensitive resin, based on computed tomography (CT) images. Before surgery, their parents received information regarding liver anatomy, physiology, tumour characteristics, planned surgery, and surgical risks using these CT images. Then, parents completed questionnaires regarding this information. Thereafter, 3D printed models of each patient were presented along with an explanation of the general printing process, and the same questionnaire was completed. The median number of correct responses in each category before and after the 3D printed model presentation was compared. Results Seven children and their 14 parents were enrolled in the study. After the presentation of 3D printed models, parental understanding of basic liver anatomy and physiology, tumour characteristics, the planned surgical procedure, and surgical risks significantly improved. Parents demonstrated improvements in their understanding of basic liver anatomy by 26.4%, basic liver physiology by 23.6%, tumour characteristics by 21.4%, the planned surgical procedure by 31.4%, and surgical risks by 27.9%. Conclusions Using 3D printed liver models improved parental education regarding the understanding of liver anatomy and physiology, tumour characteristics, surgical procedure, and associated surgical risks.