F qNMR based pharmacokinetics, metabolism and mass balance studies of SARS-CoV-2-3CL protease inhibitor simnotrelvir (SIM0417) in humans.

Simnotrelvir (SIM0417), an inhibitor of the 3CL protease of SARS-CoV-2, has been identified as a CYP3A sensitive substrate. This study investigated the pharmacokinetics, metabolism, and mass balance of simnotrelvir following a single oral dose of 750 mg in six healthy Chinese male subjects, co-administered with four doses of 100 mg ritonavir. Analysis using F qNMR combined with LC-MS/MS showed that the parent drug M0 constituted over 90% of the drug-related components in plasma.

Drug-drug interactions of simnotrelvir/ritonavir: an open-label, fixed-sequence, two-period clinical trial.

Objectives: Simnotrelvir is a small-molecule highly specific 3C-like protease inhibitor for anti-SARS-CoV-2 and was approved as a combination drug with ritonavir (simnotrelvir/ritonavir) in China. Simnotrelvir is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), and a weak inhibitor of CYP3A. Ritonavir is a substrate and inhibitor of CYP3A and an inhibitor of P-gp.

Trismus caused by migration of orthodontic archwire into the infratemporal fossa: a case report.

Introduction: Soft tissue injuries are known complications of orthodontic treatment. Most of the injuries are mild, but severe complications can arise from deeper penetration or dislodgement of brackets and other foreign bodies into the surrounding tissues of the oropharynx and infratemporal fossa.

Patient Concerns: The patient, accompanied by his parents, presented to the Children's Emergency Department with the concern of gradual limitation of mouth opening and eventual trismus, which occurred over a span of 2 weeks.

A randomized, double-blind, placebo-controlled phase II study to evaluate the efficacy and safety of ivarmacitinib (SHR0302) in adult patients with moderate-to-severe alopecia areata.

Background: Alopecia areata (AA) is a CD8+ T cell-mediated autoimmune disease characterized by nonscarring hair loss. Ivarmacitinib, which is a selective oral Janus kinase 1 inhibitor, may interrupt certain cytokine signaling implicated in the pathogenesis of AA.

Objective: To evaluate the efficacy and safety of ivarmacitinib in adult patients with AA who have ≥25% scalp hair loss.

A Phase I Study to Evaluate the Safety and Pharmacokinetics of SHR0302 Base Ointment in Healthy Adult Volunteers.

Introduction: SHR0302 is a highly selective JAK1 inhibitor. This study aimed to investigate the safety, tolerability, and pharmacokinetics of single and multiple-dose topical skin application of SHR0302 base ointment in healthy adult subjects.

Methods: This phase I clinical trial (registration number: CTR20192188) consisted of two parts.

Cleft Nasal Stent Production Using Three-Dimensional Scanning and Printing Technology.

In most cleft centers worldwide, nasal stents are routinely used in the postoperative period to prevent collapse of the lower lateral cartilage and maintain the shape of the nostrils as well as nasal alar. Prefabricated nasal stents are expensive and do not offer options for customization. In this paper, we introduce a cost-effective technique for manufacturing nasal stents using three-dimensional scanning and printing technology.

Efficacy and Safety of SHR0302, a Highly Selective Janus Kinase 1 Inhibitor, in Patients with Moderate to Severe Atopic Dermatitis: A Phase II Randomized Clinical Trial.

Background: Atopic dermatitis is a chronic, inflammatory condition causing a substantial burden to patients and caregivers. SHR0302 is an oral, highly selective, Janus kinase 1 inhibitor under investigation for inflammatory skin diseases.

Objective: The aim of this study was to investigate the efficacy and safety of SHR0302 in Chinese patients with moderate to severe atopic dermatitis.

Synthesis and biological evaluation of heteroaryl styryl sulfone derivatives as anticancer agents.

Herein we disclose a series of novel heteroaryl styryl sulfone derivatives as potential anticancer agents. Structure-activity relationships of these newly synthesised compounds were explored with respect to the significance of the position and number of nitrogen atom of the heteroaryl ring for anti-proliferative activity in human cancer cell lines. A lead compound 14f was tested against a panel of cancerous and untransformed cell lines, and found to be highly potent against cancer cells with minimal toxicity in the untransformed cells.

Efficacy and safety of once-daily inhaled umeclidinium/vilanterol in Asian patients with COPD: results from a randomized, placebo-controlled study.

Background: Combination of the inhaled long-acting muscarinic antagonist umeclidinium (UMEC; GSK573719) with the long-acting β2-agonist vilanterol (VI) is an approved maintenance treatment for COPD in the US and EU. We compared the efficacy and safety of UMEC/VI with placebo in patients with COPD of Asian ancestry.

Patients And Methods: In this 24-week, Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients were randomized 1:1:1 to UMEC/VI 125/25 μg, UMEC/VI 62.

Effects of a combination of umeclidinium/vilanterol on exercise endurance in patients with chronic obstructive pulmonary disease: two randomized, double-blind clinical trials.

Objective: Exercise intolerance is a hallmark of chronic obstructive pulmonary disease (COPD).

Methods: Patients with COPD were randomized in two multicentre, double-blind, incomplete block crossover studies. Patients received two of six treatments in sequence (12 weeks each): placebo, umeclidinium (UMEC)/vilanterol (VI) (125/25 mcg or 62.

Discovery of (E)-3-((styrylsulfonyl)methyl)pyridine and (E)-2-((styrylsulfonyl)methyl)pyridine derivatives as anticancer agents: synthesis, structure-activity relationships, and biological activities.

ON01910.Na is a highly effective anticancer agent that induces mitotic arrest and apoptosis. Clinical studies with ON01910 in cancer patients have shown efficacy along with an impressive safety profile.

Wireless transmission of neuronal recordings using a portable real-time discrimination/compression algorithm.

A design challenge of portable wireless neural recording systems is the tradeoff between bandwidth and power consumption. This paper investigates the compression of neuronal recordings in real-time using a novel discriminating Linde-Buzo-Gray algorithm (DLBG) that preserves spike shapes while filtering background noise. The technique is implemented in a low power digital signal processor (DSP) which is capable of wirelessly transmitting raw neuronal recordings.