Efficacy and safety of a combination of miglitol, metformin and insulin aspart in the treatment of type 2 diabetes

Purpose: To study the clinical effect of combining insulin aspart with different drugs in the treatment oftype 2 diabetes mellitus (T2DM).Methods: Two hundred and thirty-seven T2DM patients admitted to the Endocrinology Department of the Second Affiliated Hospital of Kunming Medical University from March to September 2018 were selected as subjects in this study. Miglitol and metformin were used in combination with insulin aspart in the treatment of T2DM. In addition, data on the effectiveness and safety of different treatment options,such as patient’s weight, waist circumference, blood glucose indicators, indices of heart, liver and kidney functions, and incidence of complications were recorded and compared between the two groups.Results: The use of a combination of miglitol and insulin aspart produced an excellent hypoglycaemic effect, and it significantly reduced the incidence of sensory neuropathy in the eyes and distal limbs (p < 0.05). The use of combination of metformin and insulin aspart effectively protected the heart and kidney, and prevented hypoglycaemia (p < 0.05).Conclusion: These results suggest that treatment with a combination of miglitol and insulin aspart is suitable for patients with T2DM whose blood sugar levels are out of control, while combined treatment with metformin and insulin aspart is more suited for patients who desire to reduce blood sugar and blood lipids through weight loss, and patients with cardiac and renal insufficiency

Endometrium metabolomic profiling reveals potential biomarkers for diagnosis of endometriosis at minimal-mild stages

Abstract Background The sensitivity and specificity of non-invasive diagnostic methods for endometriosis, especially at early stages, are not optimal. The clinical diagnostic indicator cancer antigen 125 (CA125) performs poorly in the diagnosis of minimal endometriosis, with a sensitivity of 24%. Therefore, it is urgent to explore novel diagnostic biomarkers. We evaluated the metabolomic profile variation of the eutopic endometrium between minimal-mild endometriosis patients and healthy women by ultra-high-performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS). Methods Our study comprised 29 patients with laparoscopically confirmed endometriosis at stages I-II and 37 infertile women who underwent diagnostic laparoscopy combined with hysteroscopy from January 2014 to January 2015. Eutopic endometrium samples were collected by pipelle endometrial biopsy. The metabolites were quantified by UHPLC-ESI-HRMS. The best combination of biomarkers was then selected by performing step-wise logistic regression analysis with backward elimination. Results Twelve metabolites were identified as endometriosis-associated biomarkers. The eutopic endometrium metabolomic profile of the endometriosis patients was characterized by a significant increase in the concentration of hypoxanthine, L-arginine, L-tyrosine, leucine, lysine, inosine, omega-3 arachidonic acid, guanosine, xanthosine, lysophosphatidylethanolamine and asparagine. In contrast, the concentration of uric acid was decreased. Metabolites were filtered by step-wise logistic regression with backward elimination, and a model containing uric acid, hypoxanthine, and lysophosphatidylethanolamine was constructed. Receiver-operating characteristic (ROC) analysis confirmed the prognostic value of these parameters for the diagnosis of minimal/mild endometriosis with a sensitivity of 66.7% and a specificity of 90.0%. Conclusions Metabolomics analysis of the eutopic endometrium in endometriosis was effectively characterized by UHPLC-ESI-HRMS-based metabolomics. Our study supports the importance of purine and amino acid metabolites in the pathophysiology of endometriosis and provides potential biomarkers for semi-invasive diagnosis of early-stage endometriosis

Table1_Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/β-catenin pathway.XLSX

Feiyanning Formula (FYN), a Chinese herbal formula derived from summarized clinical experience, is proven to have anti-tumor effects in lung cancer patients. Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), can improve progression-free survival and overall survival of patients but drug resistance is inevitable. The current study evaluated the effects of FYN in osimertinib-resistant HCC827OR and PC9OR cells. FYN preferentially inhibited the proliferation and migration of HCC827OR and PC9OR cells. Moreover, FYN and osimertinib exhibited synergistic inhibitory effects on proliferation and migration. Real-time qPCR (RT-qPCR) and western blotting results indicated that FYN downregulated gene and protein levels of GSK3β and SRFS1, which are enriched in the Wnt/β-catenin pathway. Besides, FYN inhibited tumor growth and exhibited synergistic effects with osimertinib in vivo. Collectively, the results suggested that FYN exerted an anti-osimertinib resistance effect via the Wnt/β-catenin pathway.</p

Image1_Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/β-catenin pathway.TIF

Feiyanning Formula (FYN), a Chinese herbal formula derived from summarized clinical experience, is proven to have anti-tumor effects in lung cancer patients. Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), can improve progression-free survival and overall survival of patients but drug resistance is inevitable. The current study evaluated the effects of FYN in osimertinib-resistant HCC827OR and PC9OR cells. FYN preferentially inhibited the proliferation and migration of HCC827OR and PC9OR cells. Moreover, FYN and osimertinib exhibited synergistic inhibitory effects on proliferation and migration. Real-time qPCR (RT-qPCR) and western blotting results indicated that FYN downregulated gene and protein levels of GSK3β and SRFS1, which are enriched in the Wnt/β-catenin pathway. Besides, FYN inhibited tumor growth and exhibited synergistic effects with osimertinib in vivo. Collectively, the results suggested that FYN exerted an anti-osimertinib resistance effect via the Wnt/β-catenin pathway.</p

Table2_Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/β-catenin pathway.XLSX

Feiyanning Formula (FYN), a Chinese herbal formula derived from summarized clinical experience, is proven to have anti-tumor effects in lung cancer patients. Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), can improve progression-free survival and overall survival of patients but drug resistance is inevitable. The current study evaluated the effects of FYN in osimertinib-resistant HCC827OR and PC9OR cells. FYN preferentially inhibited the proliferation and migration of HCC827OR and PC9OR cells. Moreover, FYN and osimertinib exhibited synergistic inhibitory effects on proliferation and migration. Real-time qPCR (RT-qPCR) and western blotting results indicated that FYN downregulated gene and protein levels of GSK3β and SRFS1, which are enriched in the Wnt/β-catenin pathway. Besides, FYN inhibited tumor growth and exhibited synergistic effects with osimertinib in vivo. Collectively, the results suggested that FYN exerted an anti-osimertinib resistance effect via the Wnt/β-catenin pathway.</p

Discovery of Phosphatidic Acid, Phosphatidylcholine, and Phosphatidylserine as Biomarkers for Early Diagnosis of Endometriosis

The sensitivity and specificity of clinical diagnostic indicators and non-invasive diagnostic methods for endometriosis at early stage is not optimal. Previous studies demonstrated that abnormal lipid metabolism was involved in the pathological development of endometriosis. Our cross-sectional study included 21 patients with laparoscopically confirmed endometriosis at stage I–II and 20 infertile women who underwent diagnostic laparoscopy combined with hysteroscopy from January 2014 to January 2015. Eutopic endometrium was collected by pipelle endometrial biopsy. Lipid metabolites were quantified by ultra-high performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS). Lipid profiles of endometriosis patients at early stage (I–II) was characterized by a decreased concentration of phosphatidylcholine (18:1/22:6), (20:1/14:1), (20:3/20:4), and phosphatidylserine (20:3/23:1) and an increased concentration of phosphatidic acid (25:5/22:6) compared with control. The synthesized predicting strategy with 5 biomarkers has a specificity of 75.0% and a sensitivity of 90.5%. Lipid profile of eutopic endometrium in endometriosis was effectively characterized by UHPLC-ESI-HRMS-based metabolomics. Our study demonstrated the alteration of phosphatidic acid, phosphatidylcholine, phosphatidylserine metabolites in endometriosis and provided potential biomarkers for semi-invasive diagnose of endometriosis at early stage