Fertility-Sparing Surgery and Adjuvant Chemotherapy with Trastuzumab Result in Complete Remission in a Young Woman with Rare Primary Mucinous Ovarian Cancer due to ERBB2 Co-amplification with CDK12 and Chromosome 11q13.3 Amplicon: A Case Report and Literature Review.

Primary mucinous ovarian carcinoma (PMOC) is a rare tumor, accounting for approximately 3% of all epithelial ovarian cancers (EOCs), with clinical risk factors and biologic features distinct from that of EOC. The prognosis for women with recurrent and high-grade PMOC remains poor, likely related to a poor response to conventional chemotherapy for EOC. A 27-year-old Chinese woman sought medical attention in January 2021 for abdominal distention from a large pelvic mass. After extensive investigations and workup, she was diagnosed with PMOC of the right ovary. Following multidisciplinary team (MDT) discussions, the patient underwent fertility-sparing surgery (FSS) (abdominal left adnexectomy, right partial oophorectomy, pelvic lymph node dissection, para-aortic lymph node dissection, omentectomy) as she yearned to preserve her fertility and the contralateral ovary appeared normal. Deep genetic analyses revealed ERBB2 co-amplification with CDK12 and chromosome 11q13.3 amplicon. Treatment with fertility-sparing surgery and adjuvant chemotherapy with trastuzumab results in complete remission. This novel strategy utilizing precise diagnostics and characterization of the histo-type of rare tumors allowed personalized targeting with optimum drug response for women who yearn fertility preservation and remission from the disease, especially when there is very limited clinical experience on management of such rare ovarian tumors.

Malignant Struma Ovarii (Papillary Carcinoma) with Hyperthyroidism: A Case Report and Literature Review.

Malignant struma ovarii (MSO) is an extremely rare monodermal ovarian teratoma. Preoperative diagnosis and intraoperative freezing diagnosis are exceedingly difficult due to the rarity of the disease and its clinically noncharacteristic manifestations with less than 200 reports in the current literature. In this paper, a case of MSO (papillary carcinoma) with hyperthyroidism was discussed in terms of its epidemiology, clinicopathology, molecular features, treatment, and prognosis.

Gut microbiota as predictors of the occurrence of high on-treatment platelet reactivity in acute ischemic stroke patients.

Introduction: In this study, we aimed to investigate the association between gut microbiota and high on-treatment platelet reactivity (HTPR) in patients with acute ischemic stroke (AIS). Methods: We enrolled a total of 48 AIS patients, including 19 HTPR patients and 29 non-high on-treatment platelet reactivity (NHTPR) patients, along with 10 healthy controls. Clinical and laboratory data, as well as stool samples, were collected from all participants. The composition and function of gut microbiota were assessed using 16S rRNA sequencing. Differences in the gut microbiota between the two groups were analyzed, and a diagnostic model based on the gut microbiota was established using random forest model. Results: HTPR patients exhibited a decreased microbial richness compared to NHTPR patients. Additionally, the relative abundance of unidentified_Clostridia and Ralstonia was lower in HTPR patients. Significant differences in biological functions, such as toxoplasmosis, were observed between the two groups. The combination of Ralstonia, unidentified-Clostridia, Mailhella, Anaerofustis, and Aggregatibacter showed excellent predictive ability for HTPR occurrence (AUC=0.896). When comparing AIS patients with healthy controls, alterations in the microbiota structure were observed in AIS patients, with imbalances in short-chain fatty acid-producing bacteria and pathogenic bacteria. Significant differences in biological functions, such as oxidative phosphorylation, were noted between the two groups. The combination of Alloprevotella, Terrisporobacter, Streptococcus, Proteus, and unidentified_Bacteria exhibited strong predictive power for AIS occurrence (AUC=0.994). Conclusions: This study is the first to uncover the microbial characteristics of HTPR in AIS patients and demonstrate the predictive potential of specific bacterial combinations for HTPR occurrence.

Scutellarin acts on the AR-NOX axis to remediate oxidative stress injury in a mouse model of cerebral ischemia/reperfusion injury.

BACKGROUND: Oxidative stress plays an important role in the pathology of ischemic stroke. Studies have confirmedthat scutellarin has antioxidant effects against ischemic injury, and we also reported that the involvement of Aldose reductase (AR) in oxidative stress and cerebral ischemic injury, in this study we furtherly explicit whether the antioxidant effect of scutellarin on cerebral ischemia injury is related to AR gene regulation and its specific mechanism. METHODS: C57BL/6N mice (Wild-type, WT) and AR knockout (AR-/-) mice suffered from transient middle cerebral artery occlusion (tMCAO) injury (1 h occlusion followed by 3 days reperfusion), and scutellarin was administered from 2 h before surgery to 3 days after surgery. Subsequently, neurological function was assessed by the modified Longa score method, the histopathological morphology observed with 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (Elisa) was used to detect the levels of ROS, 4-hydroxynonenal (4-HNE), 8-hydroxydeoxyguanosine (8-OHDG), Neurotrophin-3 (NT-3), poly ADP-ribose polymerase-1 (PARP1) and 3-nitrotyrosine (3-NT) in the ischemic penumbra regions. Quantitative proteomics profiling using quantitative nano-HPLC-MS/MS were performed to compare the protein expression difference between AR-/- and WT mice with or without tMCAO injury. The expression of AR, nicotinamide adenine dinucleotide phosphate oxidases (NOX1, NOX2 and NOX4) in the ipsilateral side of ischemic brain were detected by qRT-PCR, Western blot and immunofluorescence co-staining with NeuN. RESULTS: Scutellarin treatment alleviated brain damage in tMCAO stroke model such as improved neurological function deficit, brain infarct area and neuronal injury and reduced the expression of oxidation-related products, moreover, also down-regulated tMCAO induced AR mRNA and protein expression. In addition, the therapeutic effect of scutellarin on the reduction of cerebral infarction area and neurological function deficits abolished in AR-/- mice under ischemia cerebral injury, which indicated that the effect of scutellarin treatment on tMCAO injury is through regulating AR gene. Proteomic analysis of AR-/- and WT mice indicated AR knockout would affect oxidation reaction even as NADPH related process and activity in mice under cerebral ischemia conditions. Moreover, NOX isoforms (NOX1, NOX2 and NOX4) mRNA and protein expression were significant decreased in neurons of penumbra region in AR-/- mice compared with that in WT mice at 3d after tMCAO injury, which indicated that AR should be the upstream protein regulating NOX after cerebral ischemia. CONCLUSIONS: We first reported that AR directly regulates NOX subtypes (not only NOX2 but also NOX1 and NOX4) after cerebral ischaemic injury. Scutellarin specifically targets the AR-NOX axis and has antioxidant effects in mice with cerebral ischaemic injury, providing a theoretical basis and accurate molecular targets for the clinical application of scutellarin.

Clinical Impact of 11q13.3 Amplification on Immune Cell Infiltration and Prognosis in Breast Cancer.

Introduction: Amplification of the 11q13.3 locus has been observed in various tumors. This study sought to determine the correlation of gene amplification at the 11q13.3 locus with the immune status and survival of breast cancer. Methods: Amplification of the 11q13.3 locus was characterized by analyzing a publicly available database from the cBioPortal platform (TCGA). The correlation of amplified genes with immune cell infiltration in breast cancer was further analyzed using the TIMER2.0 platform. Immunohistochemical staining was used to determine the expression levels of Cyclin D1 (CCND1), Fas-associated death domain (FADD) and P53 in 156 clinical breast cancer samples. Results: This study revealed that amplification of the 11q13.3 amplicon in breast cancer is likely more frequently detected in luminal B breast cancer. Moreover, high expression or amplification of CCND1, fibroblast growth factor 3 (FGF3), fibroblast growth factor 4 (FGF4), fibroblast growth factor 19 (FGF19) and FADD was inversely correlated with the abundance of CD4+ T cells and dendritic cell infiltration in breast cancer (P < 0.05). Data analysis also demonstrated that high expression of CCND1, FGF4 and FADD mRNA levels was closely correlated with shorter recurrence-free survival (RFS) in patients with breast cancer (P < 0.05). The results of immunohistochemical staining from clinical samples further confirmed that high expression of CCND1 and FADD was frequently detected in luminal B and high-grade breast cancer with shorter metastasis-free survival times (P < 0.05). Conclusion: This study demonstrated that coamplification of genes located on the 11q13.3 amplicon is frequently detected in luminal B subtype breast cancer and is closely associated with worse survival in patients with breast cancer. Moreover, coamplification of the CCND1-FGF locus might decrease antitumor immune activity in breast cancer, indicating that coamplification of the 11q13.3 amplicon is likely to be a key determinant of therapeutic resistance and accelerate the aggressive evolution of breast cancer.

Dynamic changes in Beclin-1, LC3B and p62 at various time points in mice with temporary middle cerebral artery occlusion and reperfusion (tMCAO).

Ischaemic stroke is attributable to cerebrovascular disease and is associated with high morbidity, disability, mortality and recurrence. Autophagy is a critical mediator and plays dual roles in ischaemic stroke. Autophagy can protect against ischaemic brain injury during the early stage of ischaemic stroke, while excessive autophagy can induce apoptosis and exacerbate brain injury. However, the time-dependent variations in autophagy in ischaemic stroke are unknown. C57BL/6 mice were used to establish a model of temporary middle cerebral artery occlusion and reperfusion (tMCAO). The neurological functional scores and infarct volumes were determined at 1 d, 3 d, 5 d, and 7 d after modelling. The levels of Beclin-1, LC3B, p62, GFAP, TNF-α, IL-6, IL-10, ROS, 4-HNE and 8-OHDG were measured by ELISA, RT-PCR, immunofluorescence analysis and western blotting. The morphology of autophagosomes of ischaemic penumbra was observed by transmission electron microscopy (TEM). Beclin-1, LC3B, ROS, 4-HNE, 8-OHDG, GFAP, TNF-α and IL-6 levels increased (P < 0.01), while p62 and IL-10 levels decreased (P < 0.01) after tMCAO compared to those in the sham group. Beclin-1, LC3B, ROS, 4-HNE, 8-OHDG, GFAP, TNF-α and IL-6 levels were reduced in tMCAO mice at 3 d, 5 d and 7 d (P<0.05), and p62 and IL-10 levels were enhanced (P < 0.05) compared to those at 1 d. In addition, Beclin-1 positively correlated with LC3B, GFAP, TNF-α, IL-6, ROS, 4-HNE and 8-OHDG (P < 0.05), and Beclin-1 negatively correlated with p62 and IL-10 (P < 0.05). The number of autophagosomes was consistent with the expression of autophagy marker proteins, both showing a steady decrease. In summary, autophagy was activated within 7 d of tMCAO induction, and it strengthened at 1 d and then weakened steadily from 3 to 7 d. In addition, this study verified that autophagy positively correlated with the inflammatory response and oxidative stress at 7 d after tMCAO.

Effect of Hydrotalcites Interlayer Water on Pt-Catalyzed Aqueous-Phase Selective Hydrogenation of Cinnamaldehyde.

The heterogeneous hydrogenation of α,ß-unsaturated compounds requires understanding of the structure-activity relationship of metallic catalysts in consideration of solvent-mediated processes. In this work, a CoAl hydrotalcites (CoAl-HTs)-supported Pt nanoparticle catalyst is employed to study the effect of solvent water and HTs interlayer water on the aqueous-phase selective hydrogenation of cinnamaldehyde (CALD). Pt/Co2Al1-HTs catalyst displays 5075 h-1 of specific reaction rate and 89% of C═O hydrogenation selectivity at 80 °C under 20 bar of H2. Combined results of isotope-labeling experiments and theoretical DFT calculations demonstrate that the water-mediated hydrogen-exchange pathway exists in the reaction with a relatively lower-energy barrier in comparison to the direct H2-dissociated hydrogenation pathway. The results also reveal that the interlayer water species of HTs support participate in the hydrogen-exchange reaction. Based on the H2-D2 exchange results, these HTs interlayer water species can promote H2 activation and dissociation processes and thus accelerate the CALD hydrogenation reaction even under solvent-free conditions.

Roles of microRNA-206 in osteosarcoma pathogenesis and progression.

BACKGROUND AND AIMS: MicroRNA-206 has proven to be down-regulated in many human malignancies in correlation with tumour progression. Our study aimed to characterize miR-206 contributions to initiation and malignant progression of human osteosarcoma. METHODS: MiR-206 expression was detected in human osteosarcoma cell line MG63, human normal osteoblastic cell line hFOB 1.19, and paired osteosarcoma and normal adjacent tissues from 65 patients using quantitative RT-PCR. Relationships of miR-206 levels to clinicopathological characteristics were also investigated. Moreover, miR-206 mimics and negative control siRNA were transfected into MG63 cells to observe effects on cell viability, apoptosis, invasion and migration. RESULTS: We found that miR-206 was down-regulated in the osteosarcoma cell line MG63 and primary tumor samples, and decreased miR-206 expression was significantly associated with advanced clinical stage, T classification, metastasis and poor histological differentiation. Additionally, transfection of miR-206 mimics could reduce MG- 63 cell viability, promote cell apoptosis, and inhibit cell invasion and migration. CONCLUSIONS: These findings indicate that miR-206 may have a key role in osteosarcoma pathogenesis and development. It could serve as a useful biomarker for prediction of osteosarcoma progression, and provide a potential target for gene therapy.