The incidence of systemic fungal infections have increased dramatically, moreover, drug resistance including either primary (intrinsic) or secondary (acquired) resistance, becomes one of the main reasons accounting for the failure of treating invasive fungal infections in the past decades. Nowadays, clinically available antifungal drugs are limited and their combination in antifungal therapy was not effective. It is expected to be a new strategy to synergistically sensitize antifungal drugs against drug-resistant fungi by using new small molecules. Based on the study in our research group and the reported work of others, we reviewed the research of the natural products which have synergistic effect with the antifungal agents against drug-resistant fungi. This review focused on the resource, structure, pharmacological activity, and action mechanism of the compounds, as well as somewhat in common, and would provide theoretical base for seeking new drug against drug-resistance fungi.

Objective To explore the importance of diabetic education and hypoglycemia nursing for population with high risk of hypoglycemia through analysis of the personal factors influencing incidence of hypoglycemia of type 2 diabetic patients during initial use of insulin.Methods There were 257 cases of T2DM hospitalized patients during initial use of insulin,among whom 80 experienced hypoglycemia.They were divided into two groups,one was the hypoglycemia group,another was the non-hypoglycemia group.Firstly,we compared the different characteristics of the two groups such as gender,BMI and HbAlc,and so on.And then,the possible risk factors of hypoglycemia were analyzed by a Logistic regression model.Finally,the most significant factors were analyzed with the ROC curve.Results These two groups were obviously different in seven elements such as BMI,Scr,HbAlc and TG,and so on.BMI and HbAlc were the most primary causes for prevention of hypoglycemia.When patients got HbAlc＜8.65％ or BMI＜26.3 kg/m2,they had more opportunity to occur hypoglycemia.Conclusions BMI and HbAlc of patients are primary causes for hypoglycemia.It is of great significance for nurses to enhance diabetes education to the patients with HbAlc＜8.65％ or BMI＜26.3 kg/m2 to alleviate the incidence of hypoglycemia.

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.