Note On Certain Inequalities for Neuman Means

In this paper, we give the explicit formulas for the Neuman means $N_{AH}$, $N_{HA}$, $N_{AC}$ and $N_{CA}$, and present the best possible upper and lower bounds for theses means in terms of the combinations of harmonic mean $H$, arithmetic mean $A$ and contraharmonic mean $C$.Comment: 9 page

Coexistence of splenic marginal zone lymphoma with hepatocellular carcinoma: a case report

BACKGROUND: Coexistence of splenic marginal zone lymphoma with hepatocellular carcinoma is rare. Although some reports have suggested the possible pathogenic role of HBV, HCV, chronic and persistent antigenic stimulation in lymphoma, their role in causing lymphomas is still unclear. CASE PRESENTATION: We describe a hepatocellular carcinoma with concomitant splenic marginal zone lymphoma in a 64-year-old Chinese man with cirrhosis. Serum hepatitis B virus surface antigen was positive and antihepatitis C virus antibody was negative. The resected liver mass measuring 4 × 3 × 3 cm was grey and soft with a small area of bleeding, necrosis and intact capsule. Cut surface of the spleen was red-purple and had a diffuse reticulonodular appearance indicative of prominent white pulp. On histologic sections, the liver mass was well and moderately differentiated hepatocellular carcinoma, and the splenic tumor was a specific low-grade small B-cell lymphoma. Immunohistochemical staining and gene rearrangement studies supported that the splenic tumor represents a clonal B-cell lymphoma. Therefore, the diagnosis of SMZL was made from the splenic specimen. CONCLUSION: To our knowledge, this is the second case report describing coexistence of hepatocellular carcinoma and splenic marginal zone lymphoma in the course of chronic HBV infection. However, we cannot assert at present that hepatitis B virus is directly involved in splenic lymphomagenesis until more information is collected from more cases in the future

Development of Oral Fast-Disintegrating Levothyroxine Films for Management of Hypothyroidism in Pediatrics

Purpose: To develop fast disintegrating films of levothyroxine (LVX) using hydrophilic hydroxypropyl methylcellulose (HPMC), croscarmellose sodium (CCS) as superdisintegrant, and propylene glycol (PG) as a plasticizer.Methods: Fast-disintegrating films were formulated by solvent casting evaporation method using 3-factor, 2-level full factorial design. The films were evaluated for disintegration time, in vitro drug release, physical appearance, thickness, weight variation, folding endurance, drug content uniformity, The effect of concentration of dependent variables (HPMC, CCS and PG) on disintegration time and in vitro drug release was studied.Results: Suitable fast-disintegrating films were obtained using HPMC, CCS and PG. The minimum disintegration time (DT) was 15 s and maximum drug release (DR) in 1 h was 97.56 %. All independent variables selected for the study were statistically significant (p < 0.5). Increase in the concentrations of independent variables increased DR and DT.Conclusion: The findings of this study indicate that the developed fast-disintegrating film is suitable for levothyroxine in the management of hypothyroidism in pediatrics.Keywords: Hypothyroidism, Superdisintegrant, Fast-disintegrating, Levothyroxine, Oral films, Hydroxypropyl methylcellulose, Croscarmelose sodium, Propylene glyco

γ-Tocotrienol Induces Paraptosis-Like Cell Death in Human Colon Carcinoma SW620 Cells

Colorectal cancer is one of the most serious illnesses among diagnosed cancer. As a new type of anti-cancer composition from tocotrienol-rich fraction of palm oil, γ-tocotrienol is widely used in anti-cancer research. The objectives of this study were to investigate the effects of γ-tocotrienol on human colon cancer SW620 and HCT-8 cells. We showed that treatment with different concentrations of γ-tocotrienol resulted in a dose dependent inhibition of cell growth. Cell death induced by γ-tocotrienol was mediated by a paraptosis-like cell death in SW620 and HCT-8 cells. Real-time RT-PCR and western blot analyses showed that γ-tocotrienol inhibited the expression level of β-catenin, cyclin D1 and c-jun. These data suggest that a paraptosis-like cell death induced by γ-tocotrienol in SW620 cells is associated with the suppression of the Wnt signaling pathway, which offers a novel tool for treating apoptosis-resistance colon cancer

The pan-inhibitor of Aurora kinases danusertib induces apoptosis and autophagy and suppresses epithelial-to-mesenchymal transition in human breast cancer cells

Danusertib (Danu) is a pan-inhibitor of Aurora kinases and a third-generation breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (Bcr-Abl) tyrosine kinase inhibitor, but its antitumor effect and underlying mechanisms in the treatment of human breast cancer remain elusive. This study aimed to investigate the effects of Danu on the growth, apoptosis, autophagy, and epithelial-to-mesenchymal transition (EMT) and the molecular mechanisms in human breast cancer MCF7 and MDA-MB-231 cells. The results demonstrated that Danu remarkably inhibited cell proliferation, induced apoptosis and autophagy, and suppressed EMT in both breast cancer cell lines. Danu arrested MCF7 and MDA-MB-231 cells in G2/M phase, accompanied by the downregulation of cyclin-dependent kinase 1 and cyclin B1 and upregulation of p21 Waf1/Cip1, p27 Kip1, and p53. Danu significantly decreased the expression of B-cell lymphoma-extra-large (Bcl-xl) and B-cell lymphoma 2 (Bcl-2), but increased the expression of Bcl-2-associated X protein (Bax) and p53-upregulated modulator of apoptosis (PUMA), and promoted the cleavage of caspases 3 and 9. Furthermore, Danu significantly increased the expression levels of the membrane-bound microtubule-associated protein 1A/1B-light chain 3 (LC3-II) and beclin 1 in breast cancer cells, two markers for autophagy. Danu induced the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases 1 and 2 (Erk1/2) and inhibited the activation of protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways in breast cancer cells. Treatment with wortmannin (a phosphatidylinositol 3-kinase inhibitor) markedly inhibited Danu-induced activation of p38 MAPK and conversion of cytosolic LC3-I to membrane-bound LC3-II. Pharmacological inhibition and small interfering RNA-mediated knockdown of p38 MAPK suppressed Akt activation, resulting in LC3-II accumulation and enhanced autophagy. Pharmacological inhibition and small interfering RNA-mediated knockdown of Erk1/2 also remarkably increased the level of LC3-II in MCF7 cells. Moreover, Danu inhibited EMT in both MCF7 and MDA-MB-231 cells with upregulated E-cadherin and zona occludens protein 1 (ZO-1) but downregulated N-cadherin, zinc finger E-box-binding homeobox 1 (TCF8/ZEB1), snail, slug, vimentin, and β-catenin. Notably, Danu showed lower cytotoxicity toward normal breast epithelial MCF10A cells. These findings indicate that Danu promotes cellular apoptosis and autophagy but inhibits EMT in human breast cancer cells via modulation of p38 MAPK/Erk1/2/Akt/mTOR signaling pathways. Danu may represent a promising anticancer agent for breast cancer treatment. More studies are warranted to fully delineate the underlying mechanisms, efficacy, and safety of Danu in breast cancer therapy

Research on the data-driven inter-well fracture channeling identification method for shale gas reservoirs

The issue of inter-well fracture channeling in shale reservoirs is becoming increasingly prominent, significantly impacting the production of nearby wells. Therefore, it is crucial to accurately determine the location of fracture channeling in order to effectively design anti-channeling measures and optimize reservoir fracturing. In this paper, a data-driven fracture propagation model and fracture channeling identification method are established. In the model, the fracture morphology is fitted by the bottom-hole flowing pressure constraint. The bottom-hole flowing pressure (pwp) calculated by the construction pump pressure and the fluid wellbore flow is mainly considered as the real solution. The bottom-hole flowing pressure (pwf) calculated by the construction displacement and the fracture morphology is used as the constraint variable, and the fracture parameters are changed using the SPSA optimization algorithm to realize the dynamic fitting of the fracture morphology. In order to accurately describe the position of fracture channeling, the seepage radius of the fracture boundary is introduced to calculate the volume of fracture reconstruction. The volume coefficient of repeated reconstruction is used as the quantitative evaluation index of fracture channeling. This approach enables an accurate depiction of the position of fracture channeling. Finally, the model method is applied to the actual fracture channeling well. The study shows that the fracture length of the well inversion is greater than the well spacing, and there is a possibility of inter-well fracture channeling. The volume coefficient of repeated reconstruction is 8%, similar to the critical fracture channeling index. There are nine fracturing sections with fracture channeling, and the maximum fracture channeling coefficient is 14.2%. This paper successfully explains the reason for cross-well fracture channeling, and its conclusion aligns with the actual monitoring results. The proposed method in this paper effectively identifies the location of fracture channeling and offers guidance for optimizing channeling prevention in subsequent designs