Phase I study, and dosing regimen selection for a pivotal COVID-19 trial of GST-HG171.

This study is aimed to evaluate the safety, tolerability, and pharmacokinetics (PK), as well as to select an appropriate dosing regimen for the pivotal clinical trial of GST-HG171, an orally bioavailable, potent, and selective 3CL protease inhibitor by a randomized, double-blind, and placebo-controlled phase I trial in healthy subjects. We conducted a Ph1 study involving 78 healthy subjects to assess the safety, tolerability, and PK of single ascending doses (150-900 mg) as well as multiple ascending doses (MADs) (150 and 300 mg) of GST-HG171. Additionally, we examined the food effect and drug-drug interaction of GST-HG171 in combination with ritonavir through a MAD regimen of GST-HG171/ritonavir (BID or TID) for 5 days. Throughout the course of these studies, no serious AEs or deaths occurred, and no AEs necessitated study discontinuation. We observed that food had no significant impact on the exposure of GST-HG171. However, the presence of ritonavir substantially increased the exposure of GST-HG171, which facilitated the selection of the GST-HG171/ritonavir dose and regimen (150/100 mg BID) for subsequent phase II/III trials. The selected dose regimen was achieved through concentrations continuously at 6.2-9.9-fold above the levels required for protein-binding adjusted 50% inhibition (IC50) of viral replication in vitro. The combination of 150 mg GST-HG171/100 mg ritonavir demonstrated favorable safety and tolerability profiles. The PK data obtained from GST-HG171/ritonavir administration guided the selection of appropriate dose for a pivotal phase II/III trial currently in progress. (This study has been registered at ClinicalTrials.gov under identifier NCT05668897).

Highly enantioselective one-pot, three-component Mannich-type reaction catalyzed by an N,N'-dioxide-scandium(III) complex.

Mild-mannered Mannich reaction: Highly enantioselective one-pot, three-component Mannich-type reaction of aldehydes, 2-aminophenol, and ketene silyl acetal with 5 mol % of a C(2)-symmetric N,N'-dioxide-based scandium(III) triflate (2:1) complex as the catalyst was achieved under mild conditions (see scheme), which facilitated the asymmetric synthesis of biologically interesting beta-amino esters.

[Survey on the developing status of integrative Chinese and Western medicine].

In order to realize the current situation and existing problems of integrative medicine of Chinese and Western medicine (ICWM) in China, a survey with questionnaires was conducted, its contents including the viewpoint of patients, who received ICWM therapy, on ICWM and on doctors of ICWM; the condition of ICWM researches; the present development of ICWM hospital and the existing problem in these hospital, etc. by inquiry on medical workers showed that most of them considered the best approach for medical research is the modern medical or the modern scientific studying method, and more than 71.2% patients prefered ICWM therapy the treatment most willing to receive.

[Discussion on definition of "traditional Chinese medicine and western medicine integration" and "integrated traditional Chinese and western medicine"].

OBJECTIVE: To discuss the definition of "traditional Chinese medicine and western medicine integration" and "integrated traditional Chinese and western medicine". METHODS: Logic methods. RESULTS: It was found that there were a lot of problems on the definition of "traditional Chinese medicine and western medicine integration" and "integrated traditional Chinese and western medicine". CONCLUSION: The understanding of the concepts of "traditional Chinese medicine and western medicine integration" and "integrated traditional Chinese and western medicine" was improved after the extensive discussion.