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Oxaliplatin (L‐OHP), a third‐generation platinum‐based anti‐tumor drug, finds widespread application in the first‐line treatment of metastatic colorectal cancer. Despite its efficacy, the drug's usage is curtailed by a litany of side effects, with L‐OHP‐induced peripheral neuropathy (OIPN) being the most debilitating. This condition can be classified into varying degrees of severity. Employing serum metabolomics, a high‐sensitivity, high‐throughput technique, holds promise as a method to identify biomarkers for clinical assessment and monitoring of OIPN patients across different severity levels. In our study, we analyzed serum metabolites in patients with different OIPN levels using ultra‐performance liquid chromatography‐high resolution mass spectrometry. By employing statistical analyses and pathway enrichment studies, we aimed to identify potential biomarkers and metabolic pathways. Our findings characterized the serum metabolic profiles of patients with varying OIPN levels. Notably, pathway analysis revealed a significant correlation with lipid metabolism, amino acid metabolism, and energy metabolism. Multivariate statistical analysis and receiver operator characteristic curve evaluation pointed to anhalamine and glycochenodeoxycholic acid as potential biomarkers for OIPN C and A, which suggest that serum metabolomics may serve as a potent tool for exploring the metabolic status of patients suffering from diverse diseases and for discovering novel biomarkers. [ABSTRACT FROM AUTHOR]

Background: Excellent blood glucose management is a key guarantee for successful progress of surgery. However, the impact of clinical pharmacists on blood glucose management of perioperative patients needs to be further investigated. To investigate the effectiveness regarding the participation of pharmacists in blood glucose management via the informatized glucose management system (iGMS) on perioperative patients with type 2 diabetes mellitus (T2DM). Methods: The working mode of clinical pharmacists participating in blood glucose management of perioperative patients with diabetes was constructed. A total of 300 patients with T2DM who underwent elective surgery were recruited and divided into a clinical pharmacist management group (intervention group) of 150 patients (94 men and 56 women; mean age: 44.38 ± 14.03 years) and a control group of 150 patients (101 men and 49 women; mean age: 47.85 ± 12.26 years) between September 2019 to April 2020. The outcomes of perioperative blood glucose management, and healthcare indicators such as preoperative waiting time, total hospitalization time, postoperative infection rate and other indicators were analyzed statistically between the two groups. Result: In the blood glucose management team of the whole hospital, the physicians, clinical pharmacists and nurses of blood glucose management in endocrinology department were the core members, and were responsible for perioperative blood glucose management of the participants in the intervention group. All subjects had lower blood glucose after 3 days of management compared to the time of admission, and blood glucose was significantly lower in the intervention group compared to the control group (P < 0.05). As compared with the control group, subjects in intervention group demonstrated significant differences in outcome measures. The relevant parameters included preoperative blood glucose compliance rate (60.67% vs. 35.33%, P<0.05), preoperative waiting time [(5.27 ± 3.34) vs. (7.45 ± 4.38), P<0.05], length of hospitalization [(11.11 ± 4.56) vs. (14.87 ± 5.39), P<0.05], incidence of hypoglycemia (8.67% vs. 18.00%, P<0.05), incidence of hyperglycemia (32.00% vs. 62.67%, P<0.05) and postoperative infection rate (18.00% vs. 24.67%, P > 0.05). Conclusion: The involvement of clinical pharmacists in blood glucose management utilizing the iGMS can control the blood glucose level of patients with T2DM in the perioperative period more stably and effectively, thereby leading to an improvement in the quality of healthcare. [ABSTRACT FROM AUTHOR]

Recently, biomimetic nanoparticles for tumor−targeted therapy have attracted intensifying interest. Although exosomes are an excellent biomimetic material, numerous challenges are still hindering its clinical applications, such as low yield, insufficient targeting efficiency, and high cost. In this work, urinary exosomes (UEs) with high expression of CD9 and CD47 were extracted from breast cancer patients by a non−invasive method. Here, a nanotechnology approach is reported for tumor homologous targeting via CD9 and phagocytosis escape via CD47 through UE−coated poly (2−ethyl−2−oxazoline)−poly (D, L−lactide) (PEOz−PLA) nanoparticles (UEPP NPs). The cytotoxic agent doxorubicin (DOX)−loaded UEPP (UEPP−D) NPs with an initial particle size of 61.5 nm showed a burst release under acidic condition mimicking the tumor microenvironment. In vitro experiments revealed that UEPP−D NPs exhibited significantly improved cellular uptake, cytotoxicity, and apoptosis in MCF−7 cell lines as compared to DOX−loaded PEOz−PLA nanoparticles (PP−D NPs) and free DOX. More importantly, anti−phagocytosis and pharmacokinetic studies confirmed that UEPP−D NPs had superior immune escape ability and significantly prolonged the drug's bloodstream circulation in vivo. Finally, UEPP−D NPs showed a markedly higher antitumor efficacy and lower side−toxicity in MCF−7 tumor bearing nude mice model. Thus, this versatile nano−system with immune escape, homologous targeting, and rapid response release characteristics could be a promising tool for breast cancer treatment. [ABSTRACT FROM AUTHOR]

The traditional Chinese herb Rubus chingii Hu (R. chingii) is widely used in clinical practice due to its beneficial effects. Flavonoids are the important class of pharmacological substances in R. chingii , however, the molecular mechanism underlying the differences in active flavonoid contents in R. chingii at different developmental stages remain poorly understood. In this experiment, we selected four developmental stages (GG, GY, YR, RR) of R. chingii as the research material. We studied the untargeted and targeted metabolic profiles of flavonoids in different periods of R. chingii , combining full-length and comparative transcriptome analyses. Functional analyses were conducted on genes implicated in flavonoid differences. GG and RR displayed relatively higher and lower contents of flavonols, flavones, flavanols, flavanones, and isoflavonoid, respectively. RNA-seq analyses showed structural genes such as RcPAL, RcC4H, Rc4CL, RcCHS, RcCHI, RcF3H, RcF3′H, and RcFLS in flavonoid biosynthesis pathway were upregulated in GG, which were essential for the accumulation flavanones, flavones, and flavonols (effective components). qRT-PCR analyses investigated that six structural genes RcCHI, RcF3H, 2 RcCHS, and 2 Rc4CL, two TFs RcMYB308 and RcMYB123 had a consistent expression pattern with which in transcriptome. Also, an interaction network showed that the RcMYB308 could positively regulate Ka3R, Qu, Qu3G, AS, Hy, Ti through RcF3H. Furthermore, Subcellular localization analysis revealed that RcMYB308 was localization to the nucleus. In tobacco, RcMYB308 was overexpressed, resulting in higher flavonoids, RcF3H, RcF3′H, RcCHI, and RcFLS. RcMYB308 upregulated RcF3H in dual-luciferase assays. These results provide new insights for further understanding the molecular mechanism regulating flavonol biosynthesis in R. chingii fruit, and also provide a potential MYB regulator for molecular breeding of R. chingii. • Metabolic profiles with transcriptome analyses were performed in R. chingii. • GG and RR displayed relatively higher and lower contents of flavonoids. • Important structural genes in flavonoid biosynthesis were upregulated in GG. • RcMYB308 led to increased flavonols, RcF3H, RcF3′H, RcCHI, and RcFLS. • Dual-luciferase assays confirmed that RcMYB308 upregulated RcF3H. [ABSTRACT FROM AUTHOR]