Extracellular vesicles (EVs) are nanosized particles released by numerous kinds of cells, which are now increasingly considered as essential vehicles of cell-to-cell communication and biomarkers in disease diagnosis and treatment. They contain a variety of biomolecular components, including lipids, proteins and nucleic acids. These functional molecules can be transmitted between tumor cells and other stromal cells such as endothelial cells, fibroblasts and immune cells utilizing EVs. As a result, tumor-derived EVs can deliver molecules to remodel the tumor microenvironment, thereby influencing cancer progression. On the one hand, tumor-derived EVs reprogram functions of endothelial cells, promote cancer-associated fibroblasts transformation, induce resistance to therapy and inhibit the immune response to form a pro-tumorigenic environment. On the other hand, tumor-derived EVs stimulate the immune response to create an anti-tumoral environment. This article focuses on presenting a comprehensive and critical overview of the potential role of tumor-derived EVs-mediated communication in the tumor microenvironment.

Gushuling (GSL), a well-known hospital preparation composed of traditional Chinese medicine (TCM), has been widely used in the clinical treatment of osteoporosis (OP) for decades due to its remarkable therapeutic effect. However, the chemical constituents of GSL are still unclear so far, which limits the in-depth study of its pharmacodynamic material basis and further restricts its clinical application. In this study, we developed a strategy for qualitative analysis of the chemical constituents of GSL in vitro and in vivo. Based on the results of ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) and the UNIFI informatics platform, the chemical constituents of GSL can be determined quickly and effectively. By comparing the retention time, accurate mass, and fragmentation spectrum of the compounds in GSL, a total of 93 compounds were identified or preliminarily identified, including flavonoids, terpenoids, phenylpropanoids, steroids, etc. Among them, nine compounds have been confirmed by standard substances, namely epimedin A, epimedin B, epimedin C, icariin, ecdysterone, calycosin, calycosin-7-glucoside, ononin, and ginsenoside Ro. Fragment patterns and characteristic ions of representative compounds with different chemical structure types were analyzed. At the same time, 20 prototype compounds and 42 metabolites were detected in rat serum. Oxidation, hydration, reduction, dehydration, glutathione S-conjugation, and acetylcysteine conjugation were the main transformation reactions of GSL in rat serum. In this research, the rapid method to characterize the in vitro and in vivo chemical constituents of GSL can not only be used for the standardization and quality control of GSL but also be helpful for further research on its pharmacodynamic material basis.

BackgroundCefepime is a fourth generation cephalosporin antimicrobial. Its extended antimicrobial activity and infrequent tendency to engender resistance make it popular for the treatment of infections. However, proper use of cefepime has not been studied adequately. In this study, we used a retrospective cohort and a prospective cohort to evaluate the usage pattern, adverse effects and cost-effectiveness of cefepime by conducting a drug use evaluation (DUE) program in the First Affiliated Hospital of Bengbu Medical College, Anhui, China.MethodsThe DUE criteria for cefepime were established by applying literature review and expert consultation, an effective method to promote interventions that will improve patient outcomes and the cost-effectiveness of drug therapy. According to the criteria, we performed a cross-sectional retrospective (cycle A) study on 96 hospitalized patients who received cefepime treatment and a prospective (cycle B) study on 111 hospitalized patients with cefepime treatment intervention. After identifying problems with usage and completing a cefepime use evaluation for cycle A, 2 months of educational intervention among professionals were given and a more effective and rational system of cefepime use was set up. During the 2 months, the lectures were arranged and attendance of prescribers was required.ResultsThe data from cycle A showed that the biggest problem was irrational prescription of cefepime; bacterial culture and drug sensitivity tests for cefepime were also not carried out. Following 2 months of educational intervention among professionals, the results for cycle B showed that the correct indication rate was 94.59%, compared with 84.38% in cycle A. Use of bacterial culture and sensitivity tests also improved, by 88.29% in cycle B compared with 65.22% in cycle A. Compared with cycle A, the significantly improved items (P < 0.05) in cycle B were blood examination, liver function monitoring, renal function monitoring, dose and duration, dosing frequency and correct medication combinations.ConclusionsCefepime can be used appropriately for the right indications and in a cost-effective way for the majority of patients through educational intervention, including the special precautions that must be followed for appropriate dosing frequency and duration. DUE programs will become one model of hospital pharmacy care and part of the plan for continuous improvements to the quality of health care in China.