During the electroporation cell membrane conductivity increases dramatically, so the analytical model for calculating the transmembrane voltage (TMV) induced on an unpermeabilized cell membrane in suspensions can not be used in this case. An analytical model for the TMV induced on a permeabilized cell membrane in suspensions exposed to a high voltage DC pulse field was built. First, a permeabilized cell was replaced by a sphere cell having the equivalent conductivity. Then the average field inside the permeabilized cell suspensions was calculated according to the effective medium theory. Finally, based on the analytical solution for the TMV on a single unpermeabilized cell, an analytical model for the TMV on a permeabilized cell in suspensions was derived. The model shows that the TMV depends on parameters such as the external electric field, critical angle of electroporation, cell radium, conductivity of the cytoplasm, membrane and external medium, cell arrangement and cell volume fraction.
Cell Membrane Permeability ; Electric Conductivity ; Electromagnetic Fields ; Electrophysiology ; Electroporation ; Humans ; Membrane Potentials ; Models, Biological ; Pulse

Objective The purpose of this study was to develop the mechanism of vacuolar H+-ATPase regulation of vaginal microenvironment.Methods In this research,53 women were divided into three groups.Their age,serum estradiol (E2),serum follicle stimulating hormone (FSH),vaginal pH value,and mRNA expression of vacuolar H +-ATPase (VHA) on the ectocervical-vaginal epithelial cells were analyzed.Results (1) As serum E2 levels decreased,the vaginal pH values increased and VHA mRNA declined (P ＜ 0.01).(2) Immunohistochemistry scores decreased in the three groups.VHA expression decreased in human ectocervical-vaginal epithelial tissues except basal cells.(3) The expression of VHA was positive correlated with estradiol,while negative correlated with age and vaginal pH value (P ＜ 0.01).Conclusions Estradiol could regulate the genetic transcription and synthetic of VHA protein under vaginal microenvironment.

In the present study, total membrane proteins from tumor cell lines including HepG2, Hep3B2, H226, Ovcar3 and N87 were extracted and digested with LysC and trypsin. The resulting peptide lysate were pre-fractionated and subjected to untargeted quantitative proteomics analysis using a high resolution mass spectrometer. The mass spectra were processed by the MaxQuant and the protein abundances were estimated using total peak area (TPA) method. A total of 6037 proteins were identified, and the analysis resulted in the identification of 2647 membrane proteins. Of those, tumor antigens and absorption, metabolism, disposition and elimination (ADME) proteins including UDP-glucuronosyltransferase, cytochrome P450, solute carriers and ATP-binding cassette transporters were detected and disclosed significant variations among the cell lines. The principal component analysis was performed for the cluster of cell lines. The results demonstrated that H226 is closely related with N87, while Hep3B2 aligned with HepG2. The protein cluster of Ovcar3 was apart from that of other cell lines investigated. By providing for the first time quantitative untargeted proteomics analysis, the results delineated the expression profiles of membrane proteins. These findings provided a useful resource for selecting targets of choice for anticancer therapy through advancing data obtained from preclinical tumor cell line models to clinical outcomes.

Objective:To assess the prognosis of sinonasal adenoid cystic carcinoma with hard palatine invasion treated by transnasal endoscopic total maxillectomy. Methods:Clinical data of twenty-six patients with sinonasal adenoid cystic carcinoma invading hard palatine treated by transnasal endoscopic total maxillectomy between May 2014 and December 2020 was analyzed retrospectively. Survival rate, local recurrence and distant metastasis were analyzed using Kaplan-Meier method. Cox regression was used to investigate the prognosis factors. Masticatory function after maxillectomy has also been assessed using the questionnaire of patients' satisfaction about masticatory function. Results:Margins in 8 patients（30%） were positive. The median time of follow-up was 38 months（6 to 85 months）. Twenty-five patients recurred. Four patients died of distant metastasis. The 5-year overall survival rate and relapse-free survival rate was 79.5% and 89.1%, respectively. Independent predictors of outcome on multivariate analysis were positive margin（P=0.018）, recurrence（P=0.006） and distant metastasis（P=0.04）. Conclusion:Transnasal endoscopic total maxillectomy could be performed for the treatment of the sinonasal adenoid cystic carcinoma with hard palatine invasion. Positive margin, local recurrence and distant metastasis were important predictors for patients' prognosis.
Humans ; Carcinoma, Adenoid Cystic/pathology* ; Paranasal Sinus Neoplasms/pathology* ; Retrospective Studies ; Neoplasm Recurrence, Local/pathology* ; Prognosis

Drug metabolism and pharmacokinetics (DMPK) is an important branch of pharmaceutical sciences. The nature of ADME (absorption, distribution, metabolism, excretion) and PK (pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems. Tremendous progress has been made in the past decade, not only in the characterization of physiochemical properties of drugs that influence their ADME, target organ exposure, and toxicity, but also in the identification of design principles that can minimize drug-drug interaction (DDI) potentials and reduce the attritions. The importance of membrane transporters in drug disposition, efficacy, and safety, as well as the interplay with metabolic processes, has been increasingly recognized. Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs, such as peptides, oligonucleotides, and antibody-drug conjugates, necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties. In this review, we highlight some of the most notable advances in the last decade, and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.