Objective:To understand the status quo and problems of insulin application at home in patients with diabetes mellitus.Methods:Pharmacists in many hospitals across the country were organized to conduct a questionnaire survey on status quo of insulin application in patients with diabetic mellitus, so as to understand their insulin use, insulin injection behavior, insulin treatment adherence, glucose monitoring adherence, insulin preservation behavior, rate of up to target blood glucose, and the incidence of adverse reactions such as hypoglycemia. The questionnaire contained 50 questions, the accuracy rate of 21 questions related to insulin application norms was calculated, and the effect of insulin application behavior of patients on the efficacy and safety of insulin therapy was investigated.Results:Clinical pharmacists from 31 hospitals across the country participated in the questionnaire distribution and survey, and 240 valid questionnaires were returned. Among the 240 patients, 106 (44.2%) were male and 134 (55.8%) were female, aged (58±15) years; 210 (87.5%) had type 2 diabetes mellitus, 25 (10.4%) had type 1 diabetes mellitus, and 5 (2.1%) had other types; 151 (62.9%) patients were treated with one kind of insulin, 89 (37.1%) were treated with 2 kinds of insulin, and a total of 13 kinds of insulin were involved; 97.9% (235/240) of the patients had at least one wrong or irregular insulin use behavior, 75.0% (180/240) had at least one problem related to insulin treatment adherence, 70.4% (169/240) had poor glucose monitoring adherence, and 68.8% (165/240) had at least one irregular insulin preservation behavior. The rate of up to target blood glucose was only 13.8% (33/240), and the incidence of hypoglycemia was 55.8% (134/240). The total correct rates of answers to insulin use behavior and treatment adherence in patients with up to target blood glucose were significantly higher than those in patients without up to target blood glucose [71.4% (57.1%, 81.0%) vs. 61.9% (52.4%, 71.4%), P=0.045; 77.8% (55.6%, 88.9%) vs. 66.7% (55.6%, 77.8%), P=0.023], and differences in the correct rate of answers to insulin use behavior and each behavior between the patients with and without hypoglycemia were not statistically significant (all P>0.05). Conclusions:Insulin has a wide variety and similar drug names, which are easily confused, leading to medication errors. The incidence of irregular insulin injection behavior, treatment adherence, and insulin preservation behavior in patients is high, which may affect the rate of up to target blood glucose.
视网膜母细胞瘤(retinpblastorua,RB)是婴幼儿最常见的眼内恶性肿瘤,严重威胁患儿的视功能及生命安全.化疗是RB临床治疗的重要手段,但产生化疗耐药性是造成RB治疗失败的重要原因.微小RNA(miRNA)是一类长约21~23个核苷酸的非编码小分子RNA,能在转录后水平调控靶基因的表达,目前已成为肿瘤研究的热点之一.miRNA在肿瘤中表达具有组织特异性,能够参与不同肿瘤的发生发展过程.近年来研究发现,多种miRNA在RB中异常表达,可通过细胞凋亡、药物转运、自噬和长链非编码RNA(lncRNA)等调控机制,参与RB化疗耐药过程.本文对miRNA调控RB耐药的最新研究进行综述,以期为解决RB化疗耐药问题找到新的生物标志物和治疗靶点.
13a-(S)-3-pivaloyloxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (CAT3) is a novel oral anti-glioma pro-drug with a potent anti-tumor effect against temozolomide-resistant glioma. 13a(S)-3-hydroxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (PF403) is the active in vivo lipase degradation metabolite of CAT3. Both CAT3 and PF403 can penetrate the blood–brain barrier to cause an anti-glioma effect. However, PF403, which is produced in the gastrointestinal tract and plasma, causes significant gastrointestinal side effects, limiting the clinical application of CAT3. The objective of this paper was to propose a metabolism modification for CAT3 using a self-microemulsifying drug delivery system (SMEDDS), in order to reduce the generation of PF403 in the gastrointestinal tract and plasma, as well as increase the bioavailability of CAT3 in vivo and the amount of anti-tumor substances in the brain. Thus, a CAT3-loaded self-microemulsifying drug delivery system (CAT3-SMEDDS) was prepared, and its physicochemical characterization was systematically carried out. Next, the pharmacokinetic parameters of CAT3 and its metabolite in the rats’ plasma and brain were measured. Furthermore, the in vivo anti-glioma effects and safety of CAT3-SMEDDS were evaluated. Finally, Caco-2 cell uptake, MDCK monolayer cellular transfer, and the intestinal lymphatic transport mechanisms of SMEDDS were investigated in vitro and in vivo. Results show that CAT3-SMEDDS was able to form nanoemulsion droplets in artificial gastrointestinal fluid within 1 min, displaying an ideal particle size (15–30 nm), positive charge (5–9 mV), and controlled release behavior. CAT3-SMEDDS increased the membrane permeability of CAT3 by 3.9-fold and promoted intestinal lymphatic transport. Hence, the bioavailability of CAT3 was increased 79% and the level of its metabolite, PF403, was decreased to 49%. Moreover, the concentrations of CAT3 and PF403 were increased 2–6-fold and 1.3–7.2-fold, respectively, in the brain. Therefore, the anti-glioma effect in the orthotopic models was improved with CAT3-SMEDDS compared with CAT3 in 21 days. Additionally, CAT3-SMEDDS reduced the gastrointestinal side effects of CAT3, such as severe diarrhea, necrosis, and edema, and observed less inflammatory cell infiltration in the gastrointestinal tract, compared with the bare CAT3. Our work reveals that, through the metabolism modification effect, SMEDDS can improve the bioavailability of CAT3 and reduce the generation of PF403 in the gastrointestinal tract and plasma. Therefore, it has the potential to increase the anti-glioma effect and reduce the gastrointestinal side effects of CAT3 simultaneously.