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).

DESIGNING PROGRAMMABLE FERROMAGNETIC SOFT METASTRUCTURES FOR MINIMALLY INVASIVE ENDOVASCULAR THERAPY.

Minimally invasive endovascular therapy (MIET) is an innovative technique that utilizes percutaneous access and transcatheter implantation of medical devices to treat vascular diseases. However, conventional devices often face limitations such as incomplete or suboptimal treatment, leading to issues like recanalization in brain aneurysms, endoleaks in aortic aneurysms, and paravalvular leaks in cardiac valves. In this study, we introduce a new metastructure design for MIET employing re-entrant honeycomb structures with negative Poisson's ratio (NPR), which are initially designed through topology optimization and subsequently mapped onto a cylindrical surface. Using ferromagnetic soft materials, we developed structures with adjustable mechanical properties called magnetically activated structures (MAS). These magnetically activated structures can change shape under noninvasive magnetic fields, letting them fit against blood vessel walls to fix leaks or movement issues. The soft ferromagnetic materials allow the stent design to be remotely controlled, changed, and rearranged using external magnetic fields. This offers accurate control over stent placement and positioning inside blood vessels. We performed magneto-mechanical simulations to evaluate the proposed design's performance. Experimental tests were conducted on prototype beams to assess their bending and torsional responses to external magnetic fields. The simulation results were compared with experimental data to determine the accuracy of the magneto-mechanical simulation model for ferromagnetic soft materials. After validating the model, it was used to analyze the deformation behavior of the plane matrix and cylindrical structure designs of the Negative Poisson's Ratio (NPR) metamaterial. The results indicate that the plane matrix NPR metamaterial design exhibits concurrent vertical and horizontal expansion when subjected to an external magnetic field. In contrast, the cylindrical structure demonstrates simultaneous axial and radial expansion under the same conditions. The preliminary findings demonstrate the considerable potential and practicality of the proposed methodology in the development of magnetically activated MIET devices, which offer biocompatibility, a diminished risk of adverse reactions, and enhanced therapeutic outcomes. Integrating ferromagnetic soft materials into mechanical metastructures unlocks promising opportunities for designing stents with adjustable mechanical properties, propelling the field towards more sophisticated minimally invasive vascular interventions.

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.