Prediction and verifcation of the key ingredients and molecular targets of Guizhi Fuling capsule against tumour metastasis and resistance

Purpose:The well-known traditional Chinese formula Guizhi Fuling capsule(GFC)has been reported to reverse ovarian cancer drug resistance.Extrachromosomal DNA(ecDNA)plays an important role in tumour metastasis and resistance.The purpose of this study was to investigate the potential mechanisms by which GFC blocks tumour metastasis and reverses drug resistance by targeting ecDNA.Methods:CNKI and PubMed were used to obtain pharmacokinetic research data on GFC in rats,and the bioactive ingredients detected in rat serum or plasma were collected.Network databases were used to screen the abnormally expressed genes in ecDNA,tumour metastasis genes,resistance genes,and the active ingredient targets of GFC.The KOBAS3.0 database was used to enrich the KEGG pathways and GO functions;the STRING platform was used to construct the core protein interaction network;and the molecular docking online tool SwissDock was used to analyse the binding activity of the core targets and the active ingredients.RT-qPCR,Western blotting and laser confocal microscopy were used to verify the efect of the sera containing GFC on ecDNA,mRNA and protein expression of key targets.Results:Twenty-three bioactive ingredients of GFC were retrieved from PubMed and CNKI.Nine shared targets were simultaneously involved in abnormal genes in ecDNA,tumour metastasis and resistance and the active ingredient targets of GFC.GO functional analysis indicated that the cotargets involved cell proliferation,apoptotic regulation,nuclear functions,etc.The potential pathways involved in the reversal of tumour metastasis and drug resistance of GFC were the PI3K-Akt signalling,cancer,and platinum drug resistance pathways.Three shared proteins targeting ecDNA(AKT1,EGFR and MYC)stand out from the top 20 PPI targets,and all of the bioactive ingredients of GFC have strong binding afnity to the three proteins.The active ingredients can reduce the expression of MYC,EGFR and AKT1 mRNA and protein and the amount of ecDNA in drug-resistant OC cells.Conclusions:GFC targeting ecDNA to reverse tumour metastasis and drug resistance has the characteristics of multiple ingredients,multiple targets,and multiple pathways,which provides a new perspective for the development of new drugs targeting ecDNA to beneft tumour treatment.

Noninvasive treatment efficacy monitoring and dose control for high-intensity focused ultrasound therapy using relative electrical impedance variation

As an effective therapeutic modality, high-intensity focused ultrasound（HIFU） can destroy tumour tissues by thermocoagulation with less metastasis, but it is still limited by inaccurate non-invasive temperature monitoring and efficacy evaluation. A model of electrical impedance measurement during HIFU therapy was established using the temperatureimpedance relationship. Based on the simulations of acoustic pressure, temperature, and electrical conductivity, the impedance of the phantom was calculated and experimentally demonstrated for different values of acoustic power values and treatment time. We proved that the relative impedance variation（RIV） increases linearly with the increasing treatment time at a fixed acoustic power, and the relative impedance variation rate shows a linear relationship with the acoustic power.The RIV and treatment time required for HIFU treatment efficacy are inversely proportional to the acoustic power and the square of acoustic power, respectively. The favourable results suggest that RIV can be used as an efficient indicator for noninvasive temperature monitoring and efficacy evaluation and may provide new strategy for accurate dose control of HIFU therapy.

Thyroid follicular renal cell carcinoma excluding thyroid metastases:A case report

BACKGROUND Thyroid follicular renal cell carcinoma is a special type of renal cell carcinoma newly recognized in recent years.It has attracted attention because of its unique histology,immunophenotype,and clinical characteristics.It has a very low incidence,and the number of case reports available for review is limited.Moreover,a thyroid mass with type of tumour is rare.CASE SUMMARY We report a case of a renal mass with a bilateral thyroid mass that was accidentally discovered in a 60-year-old man during physical examination.B-mode ultrasound showed a hypoechoic mass in the middle and lower parenchyma of the right kidney,and computed tomography showed an iso-density shadow tumour in the right kidney.Contrast agents had a significant continuous enhancement effect on the tumour,and the enhancement was not uniform.After partial nephrectomy,pathological analysis was performed to rule out the possibility that the renal tumour was caused by thyroid tumour metastasis.Needle biopsy of the thyroid tumour confirmed that the renal cell carcinoma was not related to the thyroid tumour.The patient was alive at the last postoperative follow-up.CONCLUSION This is the third published case in which thyroid tumour biopsy was performed to confirm that thyroid follicular renal cell carcinoma is not thyroid related.