Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Three dimensional organoids-based evaluation for hepatotoxicity of the susceptible compound in Polygonum multiflorum Thunb / 药学学报

In this study, the three dimensional(3D)organoid culture system was established by liquid overlay method, and applied as an effective model to evaluate the hepatic injury of susceptible compounds in Polygonum multiflorum Thunb. Compared with the ordinary two dimensional(2D)culture of liver cells, the albumin expression of L02 cells and HepG2 cells were increased by 2.5 and 6.7 times in the 3D organoid culture system, respectively. After the cultivation of 21 days, urea generation levels of 3D culture were increased by 8.3 and 15.5 times. More importantly, HepG2 cells were more suitable to development of organoids than L02 cells. The gene expressions of phase I and II drug metabolism enzymes of HepG2 cells cultured as 3D organoids were significantly increased than that in 2D culture, such as the fold changes of CYP2C9 was up to 381.9, CYP3A4 to 87.0, CYP2D6 to 312.6. In addition, drug transporter relative genes were also up-regulated. The results demonstrated that the liver synthesis and metabolic function of the 3D model were better than that of the 2D cultured hepatocytes. The results of hepatotoxicity evaluation showed this developed model can be used to assess the hepatotoxicity of acetaminophen and other positive control drugs, which were considered with defined hepatotoxicity. On the 3D culture model, the IC50 value of repeated drug dose administration was significantly lower than that of single dose administration. However, the IC50 of 2,3,5,4'-tetrahydroxy-cis-stilbene-2-O-β-glucoside(cis-SG), which is the susceptible compound in Polygonum multiflorum Thunb., could not be detected in 2D cultured model. With the treatment of a single dose administration in organ 3D culture model, the IC50 of cis-SG was 1.9 times than that of cyclosporine A, and the IC50 of 2,3,5,4'-tetrahydroxy-trans-stilbene-2-O-β-glucoside(trans-SG)was 4.1 times than cis-SG. The hepatotoxicity results of cis-SG and trans-SG on the 3D cultures were similar to in vivo toxicity results obtained in previous work. On organ 3D culture model, the IC50 of cis-SG with repeat of administration decreased compared with that with single dose administration, suggesting that long-term medication may increase the risk of liver injury. In summary, the 3D organoid culture system can be used for a long period to preserve the capacity of liver synthesis and metabolism. The organoids were a model suitable for evaluation of mechanism of the drugs with low toxicity.

[Variation and correlation analysis on phenotypic traits of Scutellaria baicalensis from different strains].

To research the differences and correlation between Scutellaria baicalensis about phenotypic traits of different strains, 10 aboveground traits and 6 root traits of S. baicalensis in two-year-transplanted plants from 14 different strains were compared respectively, and the SPSS 17.0 statistical software was used for data analysis. It showed that phenotypic traits variation of different S. baicalensis strains was rich and the F value ranged from 3.169 to 71.58. The difference was significant between each other and germplasm 15 performs the most outstanding characters. Correlation analysis showed that there existed a significant correlation between the characters except for lateral root number, root diameter and length. The correlation coefficient between the fresh weight of root and the reed head diameter was up to 0.877. Principal component analysis showed that the average of overall yield per plant and root diameter could be used as the comprehensive reference index for germplasm evaluation. The differences and correlations in phenotypic traits of different S. baicalensis strains, provide theoretical basis for distinguishing germplasm and breeding good varieties of S. baicalensis.