AIM:To investigate the effect of protopanaxatriol(PPT)on the drug resistance of paclitaxel(PTX)-resistant human breast cancer MDA-MB-231 cells(MB231-PR cells).METHODS:The MB231-PR cells were constructed as cell models.They were treated with PPT,and incubated for a certain period of time according to the experi-mental settings.CellTiter-Glo was used to determine the viability of MB231-PR cells and MDA-MB-231 parental cells(MB231-PT cells).The change of sub-G1 phase was detected by flow cytometry.Western blot was used to evaluate the apoptosis-related proteins,such as cleaved caspase-3,cleaved poly(ADP-ribose)polymerase(PARP),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and survivin.The activity of nuclear factor-κB(NF-κB)was detected by lu-ciferase reporter assay and immunofluorescence assay.The mRNA expression levels of interleukin-6(IL-6),IL-8,chemo-kine CXC motif ligand 1(CXCL1),chemokine CC motif ligand 2(CCL2),CD44,NANOG,octamer-binding transcrip-tion factor 4(OCT4),sex-determining region Y-box 2(SOX2)and aldehyde dehydrogenase 1(ALDH1)were detected by qPCR.The protein levels of IL-6 and IL-8 were measured by ELISA.Tumor sphere formation assay was used to evaluate the characteristics of stem cells.RESULTS:(1)The viability of MB231-PR cells was suppressed by PPT treatment in a dose-dependent manner compared with MB231-PT cells(P<0.01).Besides,the viability of MB231-PR cells was de-creased after combined treatment with PPT and PTX(P<0.01),the accumulation of sub-G1 phase was induced(P<0.01),the ratio of Bax/Bcl-2 was elevated(P<0.01),and the protein levels of survivin,cleaved PARP and cleaved cas-pase-3 were increased(P<0.05).(2)After PPT treatment combined with PTX,the mRNA expression of inflammatory cy-tokines(IL-6,IL-8,CXCL1 and CCL2)and cancer stem cell-related markers(OCT4,SOX2,NANOG,ALDH1 and CD44)was reduced(P<0.05),and the protein levels of IL-6 and IL-8 were decreased(P<0.01).The activity of NF-κB in MB231-PR cells was suppressed(P<0.05),and the growth of tumor spheres from MB231-PR cells was damaged(P<0.05).(3)Immunofluorescence assay showed that PTX induced nuclear p-p65 expression,but this effect was attenuated by PPT.CONCLUSION:Combined treatment with PPT and PTX could attenuate PTX resistance of MB231-PR cells by inhibiting inflammatory cytokines and cancer stem cells.

Arteriovenous malformations(AVMs)are a kind of high-flow vascular malformation.AVMs can be classified in many ways,including histo-embryological classification,hemodynamic classification,etc.At present,the two mainstream classification systems used to guide the embolization treatment of peripheral AVMs are proposed by Cho and Yakes respectively based on the angiographic morphology of the lesions.Interventional embolization is the first-line treatment for AVMs.Among the many embolization agents,absolute ethanol is a permanent liquid embolization agent.Absolute ethanol can directly destroy the vascular endothelial cells to achieve a good curative efficacy,therefore,it has been wildly used in the treatment of peripheral AVMs.Yakes classification combines the angiographic classification with absolute ethanol embolization therapy.During absolute ethanol treatment,close attention should be paid to the occurrence of complications such as elevated pulmonary artery pressure.Although there are challenges remaining in the treatment of AVMs,the rapid development of molecular genetics has made targeted drug adjunctive treatment for AVMs possible.Perhaps,the novel therapeutic mode of combination use of traditional therapy targeted drug may be able to make a breakthrough in the treatment of AVMs.

Severe insulin resistance syndrome associated with mutations in the insulin receptor(INSR) gene is rare in clinical practice. We report a 13-year-old female patient with insulin resistance, acanthosis nigricans, and Class Ⅱ malocclusion, whose family history included hyperinsulinemia in both her mother and grandmother. Whole-exome sequencing and PCR-Sanger validation identified a novel INSR mutation, c. 637delA(p.S213Vfs*69), resulting in a pathogenic variant that substitutes serine at position 213 with valine. This case highlights a clinical phenotype that is challenging to differentiate between Rabson-Mendenhall syndrome and A-type insulin resistance syndrome. Long-term follow-up is crucial to assess disease progression and prognosis.

Severe insulin resistance syndrome associated with mutations in the insulin receptor(INSR) gene is rare in clinical practice. We report a 13-year-old female patient with insulin resistance, acanthosis nigricans, and Class Ⅱ malocclusion, whose family history included hyperinsulinemia in both her mother and grandmother. Whole-exome sequencing and PCR-Sanger validation identified a novel INSR mutation, c. 637delA(p.S213Vfs*69), resulting in a pathogenic variant that substitutes serine at position 213 with valine. This case highlights a clinical phenotype that is challenging to differentiate between Rabson-Mendenhall syndrome and A-type insulin resistance syndrome. Long-term follow-up is crucial to assess disease progression and prognosis.