[Nationwide survey on clinical treatment of coronavirus disease 2019 in 9 provinces and municipalities].

OBJECTIVE: To investigate the clinical treatment and assess the knowledge and use of the coronavirus disease 2019 (COVID-19) treatment plan issued by the nation. METHODS: A nationwide questionnaire survey on line was administered to medical staffs involved in COVID-19 treatment on February 28th, 2020. The questionnaire included drug treatment, respiratory support therapy, sedation and analgesia, continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO), etc. RESULTS: There were 1 103 respondents, of whom 699 (504 doctors and 195 nurses) participated in the treatment of COVID-19. Finally, 432 doctors and 170 nurses from 9 provinces submitted valid questionnaires. The results of the questionnaire surveys of doctors and nurses were basically the same. Considering that doctors dominated in the diagnosis and treatment of COVID-19, the results of the questionnaires of doctors were mainly analyzed. The doctors participating in the survey were mainly from Hubei (29.2%), followed by Henan (24.5%), Guizhou (22.7%), and Guangxi (14.6%), etc. 55.4% of the doctors came from tertiary three hospitals, and most of them have senior titles (56.4%). 232 doctors (53.7%) participated in the treatment of mild COVID-19, and 200 doctors (46.3%) participated in the treatment of severe and critically ill patients. More than 95% of the doctors expressed that they would carry out antiviral treatment for patients with COVID-19 regardless of disease severity. The main antiviral drugs included α-interferon (69.5%), lopinavir/ritonavir (65.0%), abidol (60.0%), and ribavirin (55.7%). The choice of antiviral drugs was highly consistent with the national treatment programs of COVID-19. At the same time, 95.5% of doctors would routinely prescribe antibiotics to severe and critically ill patients. 94.0% of doctors agreed to prescribe low-dose glucocorticoid therapy to severe and critically ill patients. About 2/3 of doctors would perform lung recruitment or prone position treatment for critical patients with invasive ventilation. 79.0% of doctors preferred to use deep sedation for patients with invasive ventilation. About 1/3 of doctors believed that CRRT should be initiated early, and nearly 1/3 of doctors suggested that ECMO should be used more aggressively in critically ill patients. CONCLUSIONS: Medical staffs are familiar with the national treatment plan of COVID-19 and willing to follow it. However, as a new disease, we have limited knowledge about COVID-19 and there are still many controversies. Further practical training is needed to make clinicians more aware of the disease, and more evidence-based evidence is needed to guide clinical treatment.

Solubility and Stability Advantages of a New Cocrystal of Berberine Chloride with Fumaric Acid.

BBC is a drug with a variety of activities but poor solubility. Cocrystal technology is an effective method to improve the solubility and stability of this type of compound. In this work, the cocrystal of BBC with fumaric acid was obtained at a stoichiometric ratio of 2:1. Studies on stabilities and solubilities were carried out using BBC dihydrate and tetrahydrate as reference materials. Results showed that this new cocrystal did not only significantly improve the dissolution rate of BBC but also highly improved the stability in high humidity and temperature. Given that the cocrystals formed by BBC as the host molecule were few, different techniques were applied for characterization and structural analyses. Moreover, theoretical calculations were performed on weak interactions, such as hydrogen bonding and π-π stacking interactions, which provided the research data for the study of this kind of cocrystal.

Development and validation of a micellar electrokinetic capillary chromatography method for the determination of goserelin and related substances.

An MEKC method for the analysis of goserelin and related substances has been developed using a combination of additives including CTAB, ß-CD, and sodium hexanesulfonate. For this assay, the running buffer (pH and additives) and separation conditions (voltage and temperature) were optimized. The optimized system was the following: 200 mM 6-aminocaproic acid buffer (pH 4.2) supplemented with 175 mM CTAB, 3.0% w/v ß-CD, and 20 mM sodium hexanesulfonate; the voltage was 10 kV in reverse polarity mode, the temperature was 20°C, and UV detection was measured at 220 nm. The method was qualified by evaluating the specificity, precision, linearity, accuracy, LOD, and LOQ. According to validation experiments, the optimized method was specific, accurate, and repeatable and satisfied the requirements for the analysis of goserelin and related substances. Compared with the RP-HPLC method, the MEKC method better solved the problem of overlapping impurity signals, and the migration time required was shorter. This method can be used for quality control and for the analysis of goserelin and its related substances.

Charge profiling and stability testing of biosimilar by capillary isoelectric focusing.

CIEF was developed for the rapid analysis of charge heterogeneity of trastuzumab biosimilar using commercially available fluorocarbon-coated capillary. The CIEF master mix was composed of 0.30% w/v methyl cellulose, 2.3 M urea, 56.8 mM l-arginine, 1.52 mM iminodiacetic acid, 4.5% v/v carrier ampholytes (broad-range pI 3-10 and narrow-range pI 8-10.5 with ratio of 3:1), and 0.45% v/v 10.0, 9.5, 7.0, 5.5, 4.1 pI markers. To get a robust method to analyze charge heterogeneity, some separation parameters, including focusing time and separation temperature, were investigated and optimized. The optimized method gave good precision in estimated pI values of charge variants with RSDs of not more than 0.16% intraday analysis (n = 6) and < 0.18% interday analysis (n = 9). In addition, the applications of this method including purity, stability, lot consistency, peptide N-glycosidase F digest, and C-terminal lysine variants characterization were also investigated.