Case report: Oxaliplatin-induced idiopathic non-cirrhotic portal hypertension: a case report and literature review

Oxaliplatin has become a widely used agent in neoadjuvant chemotherapy for gastrointestinal tract tumors and is an integral part of the therapeutic approach for managing colorectal cancer recurrences and metastases, resulting in a more favorable prognosis for patients. Nevertheless, oxaliplatin can give rise to idiopathic non-cirrhotic portal hypertension (INCPH). The emergence of INCPH can disrupt tumor chemotherapy and incite persistent adverse reactions in later stages, significantly complicating clinical management. Consequently, we have presented a case report of INCPH induced by oxaliplatin chemotherapy with the aim of advancing the diagnosis and treatment of this condition, with a particular focus on the clinical manifestations. This study has ascertained that the condition is primarily attributed to complications related to portal hypertension, such as gastrointestinal bleeding, splenomegaly, and hypersplenism. The pathological features primarily involve hepatic sinus dilation and congestion, portal obstruction, absence, stenosis, shunting, localized venous and perisinusoidal fibrosis, as well as hepatocellular atrophy. Treatment primarily concentrates on strategies typically employed for cirrhosis. Endoscopic ligation, sclerotherapy, and non-selective beta-blockers (NSBBs) can be selected to prevent and treat variceal hemorrhage. Transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation can also be chosen for severe cases. Notably, despite the timely discontinuation of oxaliplatin, most patients continue to experience disease progression, ultimately resulting in a poor prognosis due to either tumor advancement or the ongoing progression of portal hypertension. This emphasizes the importance for physicians to be aware of and consider the risk of INCPH when prescribing oxaliplatin

DEFEM Method and Its Application in Pebble Flows

Based on the concept of embedded discrete elements (EDEs), the discrete element-embedded finite element model (DEFEM) is extended in this work. The new method can be used to calculate the motion and stress variation of particles. This work discusses its application in granular flow simulation for particle motions with small deformations. The updated Lagrangian finite element method is used to obtain the coupling solution of the internal stress and the overall motion of particles in the DEFEM. The computation of deformation displacement is based on the concepts of displacement decomposition (translational and rotational motions and deformation displacement). The deformation displacement is the difference between particles and template particles [rigid body, using the discrete element method (DEM) to calculate translational and rotational displacements]. It is used to calculate the dynamic stress distribution of particles and the internal force of the node. Therefore, it has a wide scope of application (for example, it can be extended to non-spherical particles). The software validation proves the accuracy of this method. The application of the DEFEM in the accumulation process of particles is given. The motion characteristics and deformation of particles are discussed, and the stress distribution and force chain structure in particle accumulation are obtained

SOX9-PDK1 axis is essential for glioma stem cell self-renewal and temozolomide resistance

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with limited therapeutic options. Glioma stem cell (GSC) is thought to be greatly responsible for glioma tumor progression and drug resistance. But the molecular mechanisms of GSC deriving recurrence and drug resistance are still unclear. SOX9 (sex-determining region Y (SRY)-box9 protein), a transcription factor expressed in most solid tumors, is reported as a key regulator involved in maintaining cancer hallmarks including the GSCs state. Previously, we have observed that silencing of SOX9 suppressed glioma cells proliferation both in vitro and in vivo. Here, we found that SOX9 was essential for GSC self-renewal. Silencing of SOX9 down-regulated a broad range of stem cell markers and inhibited glioma cell colony and sphere formation. We identified pyruvate dehydrogenase kinase 1 (PDK1) as a target gene of SOX9 using microarray analyses. PDK1 inactivation greatly inhibited glioma cell colony and sphere formation and sensitized glioma spheres to temozolomide (TMZ) toxicity. In addition, SOX9-shRNA and PDK1 inhibitor could greatly sensitize GSC to TMZ in vivo. Taken together, our data reveals that SOX9-PDK1 axis is a key regulator of GSC self-renewal and GSC temozolomide resistance. These findings may provide help for future human GBM therapy

Hexokinase 2 (HK2), the tumor promoter in glioma, is downregulated by miR-218/Bmi1 pathway

In cancer, glycolysis driving enzymes and their regulating microRNAs are one of the key focus of oncology research lately. The glycolytic enzyme hexokinase 2 (HK2) is crucial for the Warburg effect in human glioma, the most common malignant brain tumor. In the present study, we studied the tumorigenic role of HK2 in glioma, and clarified the mechanism of miR-218 induced HK2 regulation in glioma development. The HK2 expression in patient derived glioma and non neoplastic brain tissue was quantified. The HK2 silenced U87 and U251 cell lines were assessed for their proliferation, migration and invasive potential in vitro, while the tumor forming potential of U87 cells was evaluated in vivo. The untreated cell lines served as control. The HK2 expression in (a) lentivirus-infected, miR-218 overexpressing and (b) shRNA mediated Bmi1 silenced U87 and U251 glioma cell lines were quantified. Luciferase reporter assay, qRT-PCR analysis and WB were employed as required. The HK2 expression was significantly increased in glioma tissues comparing with the non neoplastic brain tissues and was positively correlated with the glioma grade. Silencing HK2 in glioma cell lines significantly decreased their proliferation, migration, invasion and tumorigenic abilities. Although, overexpression of miR-218 significantly downregulated the HK2 expression, luciferase reporter assay failed to show HK2 as the direct target of miR-218. A direct correlation, however, was observed between HK2 and Bmi-1, the direct target of miR-218. Taken together, our findings confirmed the tumorigenic activity of HK2 in glioma, and the involvement of the miR218/Bmi1 pathway in the regulation of its expression

CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription

Epigenetic alterations have been functionally linked to ovarian cancer development and occurrence. The CXXC zinc finger protein 1 (CFP1) is an epigenetic regulator involved in DNA methylation and histone modification in mammalian cells. However, its role in ovarian cancer cells is unknown. Here, we show that CFP1 protein is highly expressed in human ovarian cancer tissues. Loss of CFP1 inhibited the growth of human ovarian cancer cells, promoted apoptosis, and increased senescence. CFP1 knockdown resulted in reduced levels of SETD1 (a CFP1 partner) and histone H3 trimethylation at the fourth lysine residue (H3K4me3). RNA-sequencing revealed that deletion of CFP1 resulted in mRNA reduction of bone marrow stromal cell antigen 2 (BST2). Bioinformatics analysis and chromatin immunoprecipitation showed that CFP1 binds to the promoter of BST2 and regulates its transcription directly. Overexpression of BST2 rescued the growth inhibitory effect of CFP1 loss. Furthermore, depletion of cullin-RING ubiquitin ligases 4 (CRL4) components ROC1 or CUL4A had significantly inhibited the expression of CFP1 and BST2 similar to MLN4924 treatment that blocked cullin neddylation and inactivated CRL4s. In conclusion, CFP1 promotes ovarian cancer cell proliferation and apoptosis by regulating the transcription of BST2, and the expression of CFP1 was affected by CRL4 ubiquitin ligase complex

Contextualizing the Revised Patient Perception of Patient-Centeredness (Pppc-R) Scale in Primary Healthcare Settings: a Validity and Reliability Evaluation Study

BACKGROUND: An English version of the Patient Perception of Patient-Centeredness (PPPC) scale was recently revised, and it is necessary to test this instrument in different primary care populations. AIM: This study aimed to assess the validity and reliability of a Chinese version of the PPPC scale. DESIGN: A mixed method was used in this study. The Delphi method was used to collect qualitative and quantitative data to address the content validity of the PPPC scale by calculating the Content Validity Index, Content Validity Ratio, the adjusted Kappa, and the Item Impact Score. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were used to assess the construct validity of the PPPC scale through a cross-sectional survey. The internal consistency was also assessed. SETTING/PARTICIPANTS: In the Delphi consultation, seven experts were consulted through a questionnaire sent by email. The cross-sectional survey interviewed 188 outpatients in Guangzhou city and 108 outpatients in Hohhot City from community health service centers or stations face-to-face. RESULTS: The 21 items in the scale were relevant to their component. The Item-level Content Validity Index for each item was higher than 0.79, and the average Scale-level content validity index was 0.97 in each evaluation round. The initial proposed 4-factor CFA model did not fit adequately. Still, we found a 3-factor solution based on our EFA model and the validation via the CFA model (model fit: [Formula: see text], P \u3c 0.001, RMSEA = 0.044, CFI = 0.981; factor loadings: 0.553 to 0.888). Cronbach\u27s α also indicated good internal consistency reliability: The overall Cronbach\u27s α was 0.922, and the Cronbach\u27s α for each factor was 0.851, 0.872, and 0.717, respectively. CONCLUSIONS: The Chinese version of the PPPC scale provides a valuable tool for evaluating patient-centered medical service quality

Unveiling the Mechanism of Plasma-Catalytic Low-Temperature Water–Gas Shift Reaction over Cu/γ-Al₂O₃ Catalysts

The water-gas shift (WGS) reaction is a crucial process for hydrogen production. Unfortunately, achieving high reaction rates and yields for the WGS reaction at low temperatures remains a challenge due to kinetic limitations. Here, nonthermal plasma coupled to Cu/γ-Al2O3 catalysts was employed to enable the WGS reaction at considerably lower temperatures (up to 140 °C). For comparison, thermal-catalytic WGS reactions using the same catalysts were conducted at 140-300 °C. The best performance (72.1% CO conversion and 67.4% H2 yield) was achieved using an 8 wt % Cu/γ-Al2O3 catalyst in plasma catalysis at ∼140 °C, with 8.74 MJ mol-1 energy consumption and 8.5% H2 fuel production efficiency. Notably, conventional thermal catalysis proved to be ineffective at such low temperatures. Density functional theory calculations, coupled with in situ diffuse reflectance infrared Fourier transform spectroscopy, revealed that the plasma-generated OH radicals significantly enhanced the WGS reaction by influencing both the redox and carboxyl reaction pathways

A novel “holey-LFP / graphene / holey-LFP” sandwich nanostructure with significantly improved rate capability for lithium storage

The development of high-performance and new-structure electrode materials is vital for the wide application of rechargeable lithium batteries in electric vehicles. In this work, we design a special composite electrode structure with the macroporous three-dimensional graphene areogel framework supporting mesoporous LiFePO4 nanoplate. It is realized using a simple sol-gel deposition method. The highly conductivity graphene nanosheets assemble into an interconnected three-dimensional macroporous areogel framework, while LiFePO4 grows along the graphene nanosheets and generates a mesoporous nanoplate structure. In comparison with LiFePO4, this unique sandwich nanostructure offers a greatly increased electronic conductivity thanks to the framework of graphene nanosheets. Also, the bimodal porous structure of the composite remarkably increases the interface between the electrode/electrolyte and facilitates the transport of Li+ throughout the electrode, enabling the superior specific capacity, rate characteristic and cyclic retention