Synthesis of Fully Substituted Difluoromethylpyrazoles by Cyclization of Difluoroacetohydrazonoyl Bromides with 2-Acylacetonitriles or Malononitrile.

A concise and efficient method for the construction of fully substituted difluoromethylpyrazoles is achieved by a cyclization reaction between difluoroacetohydrazonoyl bromides and 2-acylacetonitrile or malononitrile. The method features advantages such as mild reaction conditions, broad substrate scope, good product yields, and high regioselectivity.

Preferences of patients with diabetes mellitus for primary healthcare institutions: a discrete choice experiment in China.

OBJECTIVES: To quantify the preference of patients with diabetes mellitus (DM) for primary healthcare (PHC) institutions in China to redirect the patient flow and improve health outcomes. DESIGN: Cross-sectional study. Discrete choice experiment (DCE) surveys asked patients with DM to choose between hypothetical institutions that differed in the medical service capacity, out-of-pocket (OOP) medical costs per month, travel time, the attitude of medical staff and the availability of diabetes drugs. SETTING: Shandong province, China. PARTICIPANTS: The participants were 887 patients with DM from 36 urban communities and 36 rural villages in Shandong province. One participant did not provide any DCE answers and a further 57 patients failed the internal consistency test. 829 fully completed surveys were included in the final data analysis. MAIN OUTCOMES AND MEASURES: A mixed logit model was used to calculate the willingness to pay and predict choice probabilities for PHC institution attributes. Preference heterogeneity was also investigated. RESULTS: All five attributes were associated with the preferences of patients with DM. The OOP medical costs and the medical service capacity were the most influential attributes. Improvements simultaneously in the attitude of medical staff, drug availability and travel time increased the likelihood of a patient's PHC institution choice. Preferences differed by region, annual household income and duration of diabetes. CONCLUSIONS: Our patient preference data may help policymakers improve health services and increase acceptance of choosing PHC institutions. The OOP medical costs and medical service capacity should be regarded as a priority in decision-making.

Preferences for Patients with Type 2 Diabetes Mellitus for Medications in Shandong Province, China: A Discrete Choice Experiment.

Purpose: To evaluate preferences for medications among patients with type 2 diabetes mellitus (T2DM) from urban community health stations or rural village clinics in Shandong province, China. Methods: We use a discrete choice experiment (DCE) to measure the medication preferences. Each patient completed six DCE choice sets. The attributes for the DCE questionnaire include mode of administration, out-of-pocket medication cost per month, fasting blood glucose control effect and frequency of hypoglycemia events. The conditional logit model (Clogit) and mixed logit model (MXL) were used to evaluate choice data. Results: A total of 887 patients with T2DM completed the survey. The mean age of participants was 64 years, 36.42% experienced complications, and the mean duration of diabetes was about 8 years. Overall, patients' ideal medication would not have hypoglycemia events, provide normal fasting glucose levels, have oral medication three times a day and lower monthly medication cost. Patients prioritized the frequency of hypoglycemia events (ß=15.055, P < 0.01) and were willing to spend CNY 393.10 per month to avoid hypoglycemia events. For patients with higher educational levels and with longer diagnosis time, the effect of fasting blood glucose was more relevant than all other outcomes. Conclusion: This study provides information on T2DM patients' preference for medications. Our results suggest that clinical doctors should present patients with a variety of pharmaceutical characteristics and include their preference into medication decision, which will improve patient adherence and health outcomes.

RGS1 serves as an antitumor target to inhibit proliferation of NICN87-DR cells and tumor growth in the gastric cancer mouse model.

Gastric cancer is becoming the 4th leading cause of cancer-associated death worldwide. The purpose of this study was to investigate the role of RGS1 in gastric cancer in vitro and in vivo. Proliferation, migration, invasion, and colony formation of NCIN87 cells and drug-resistant NCIN87 cells (NCIN87-DR) were determined. Cell apoptosis and cell cycle were examined using a flow cytometry assay. RGS1 gene knock-down vector (pLVshshRGS1) and Xenograft tumor mouse model was generated. RGS1 and epithelial-mesenchymal transition (EMT) associated markers, including E-cadherin (E-cad), N-cadherin (N-cad), Slug, and Vimentin were detected using a western blotting assay. Tumor size of Xenograft tumor mouse was measured and Ki67 expression was detected using the immunohistochemical assay. NCIN87-DR cells demonstrated significantly lower proliferation, migration, and invasion compared to those of NCIN87 cells (p < 0.05). NCIN87-DR cells showed obvious early apoptosis and displayed obvious alterations for the cell cycle. NCIN87-DR cells exhibited predominantly higher RGS1 expression than that in NCIN87 cells (p < 0.01). E-cad expression was markedly decreased (p < 0.01) and N-cad (p < 0.05), Slug (p < 0.01), Vimentin (p < 0.05) expressions were significantly increased in NCIN87-DR cells than those in NCIN87 cells. RGS1 gene silence remarkably reduced NCIN87-DR proliferation compared to that in NCIN87-DR cells without treatment (p < 0.01). RGS1 gene-silenced NCIN87-DR cell immunization predominantly inhibited tumor growth in Xenograft tumor mouse than that without RGS1 silence (p < 0.05). RGS1 gene-silenced NCIN87-DR cell immunization significantly downregulated Ki67 expression in tumor tissues compared with that without RGS1 silence. In conclusion, RGS1 gene silence reduced the proliferation of NCIN87-DR cells in vitro and inhibited tumor growth in vivo. Therefore, RGS1 served as an antitumor target for the gastric cancer treatment.