Vortioxetine for depression in adults: A systematic review and dose-response meta-analysis of randomized controlled trials.

AIM: Major depressive disorder (MDD) is a prevalent psychiatric condition and vortioxetine offers promising antidepressant effects due to its unique pharmacological profile. However, the dose-response relationships of vortioxetine for MDD is not well established. We aimed to conduct dose-response meta-analyses to fill this gap. METHODS: We systematically searched multiple electronic databases for randomized controlled trials of vortioxetine for MDD, with the last search conducted on 08 February, 2024. The dose-response relationship was evaluated using a one-stage random-effects dose-response meta-analysis with restricted cubic spline model. The primary outcome was efficacy (mean change in depression scale score), with secondary outcomes including response, dropout for any reasons (acceptability), dropout for adverse events (tolerability), and any adverse events (safety). RESULTS: The dose-response meta-analysis comprised 16 studies, with 4,294 participants allocated to the vortioxetine group and 2,299 participants allocated to the placebo group. The estimated 50% effective dose was 4.37 mg/day, and the near-maximal effective dose (95% effective dose) was 17.93 mg/day. Visual inspection of the dose-efficacy curve suggests that a plateau possibly had not been reached yet at 20 mg/day. Acceptability, tolerability and safety decreased as the dose increased. Subgroup analysis indicated that no significant differences were observed in acceptability, tolerability and safety among the dosage groups. CONCLUSIONS: Vortioxetine may potentially provide additional therapeutic benefits when exceeding the current licensed dosage without significantly impacting safety. Conducting clinical trials exceeding the current approved dosage appears necessary to fully comprehend its efficacy and risk.

Serum metabolomics analyses reveal biomarkers of osteoporosis and the mechanism of Quanduzhong capsules.

With the aging of the population, the prevalence of osteoporosis (OP) is rising rapidly, making it an important public health concern. Early screening and effective treatment of OP are the primary challenges facing the management of OP today. Quanduzhong capsule (QDZ) is a single preparation composed of Eucommia ulmoides Oliv., which is included in the Pharmacopoeia of the People's Republic of China. It is used to treat OP in clinical practice, but its mechanisms are unclear. This study involved 30 patients with OP, 30 healthy controls (HC), and 28 OP patients treated with QDZ to identify potential biomarkers for the early diagnosis of OP and to investigate the potential mechanism of QDZ in treating OP. The serum samples were analyzed using targeted amino acid metabolomics. Significant differences in amino acid metabolism were identified between the OP cohort and the HC group, as well as between OP patients before and after QDZ treatment. Compared with HC, the serum levels of 14 amino acids in OP patients changed significantly. Kynurenine, arginine, citrulline, methionine, and their combinations are expected to be potential biomarkers for OP diagnosis. Notably, QDZ reversed the changes in levels of 10 amino acids in the serum of OP patients and significantly impacted numerous metabolic pathways during the treatment of OP. This study focuses on screening potential biomarkers for the early detection of OP, which offers a new insight into the mechanism study of QDZ in treating OP.

Targeted arginine metabolomics combined with metagenomics revealed the potential mechanism of Pueraria lobata extract in treating myocardial infarction.

The extraction methods for traditional Chinese medicine (TCM) may have varying therapeutic effects on diseases. Currently, Pueraria lobata (PL) is mostly extracted with ethanol, but decoction, as a TCM extraction method, is not widely adopted. In this study, we present a strategy that integrates targeted metabolomics, 16 s rDNA sequencing technology and metagenomics for exploring the potential mechanism of the water extract of PL (PLE) in treating myocardial infarction (MI). Using advanced analytical techniques like ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we comprehensively characterized PLE's chemical composition. Further, we tested its efficacy in a rat model of MI induced by ligation of the left anterior descending branch of the coronary artery (LAD). We assessed cardiac enzyme levels and conducted echocardiograms. UPLC-MS/MS was used to compare amino acid differences in serum. Furthermore, we investigated fecal samples using 16S rDNA sequencing and metagenomic sequencing to study intestinal flora diversity and function. This study demonstrated PLE's effectiveness in reducing cardiac injury in LAD-ligated rats. Amino acid metabolomics revealed significant improvements in serum levels of arginine, citrulline, proline, ornithine, creatine, creatinine, and sarcosine in MI rats, which are key compounds in the arginine metabolism pathway. Enzyme-linked immunosorbent assay (ELISA) results showed that PLE significantly improved arginase (Arg), nitric oxide synthase (NOS), and creatine kinase (CK) contents in the liver tissue of MI rats. 16 s rDNA and metagenome sequencing revealed that PLE significantly improved intestinal flora imbalance in MI rats, particularly in taxa such as Tuzzerella, Desulfovibrio, Fournierella, Oscillibater, Harryflintia, and Holdemania. PLE also improved the arginine metabolic pathway in the intestinal microorganisms of MI rats. The findings indicate that PLE effectively modulates MI-induced arginine levels and restores intestinal flora balance. This study, the first to explore the mechanism of action of PLE in MI treatment considering amino acid metabolism and intestinal flora, expands our understanding of the potential of PL in MI treatment. It offers fresh insights into the mechanisms of PL, guiding further research and development of PL-based medicines.

Microfracture Lateral to the Greater Tuberosity of the Humerus Enhances Tendon-to-Bone Healing in a Rat Rotator Cuff Model.

BACKGROUND: Microfracture at the rotator cuff insertion is an established surgical marrow-stimulation technique for enhancing rotator cuff healing. However, the effect of lateralized or medialized microfracture on the insertion is unknown. PURPOSE: To compare the biomechanical and histologic effects of microfracture at 3 different regions for rotator cuff repair in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 72 Sprague-Dawley rats with bilateral supraspinatus tendon insertion detachment were allocated into 4 groups with 4 different interventions: no microfracture at the humeral head as a control group (Con), traditional microfracture at the footprint area (MFA), and medialized microfracture to the footprint area (MMFA) on the articular surface of the humerus or lateralized microfracture to the footprint area at the greater tuberosity (LMFA). All underwent immediate repair. Tendon-to-bone healing was assessed by biomechanical and histologic tests 4 and 8 weeks postoperation. RESULTS: At 4 weeks, the LMFA group showed a significantly superior failure load compared with the other groups (all P < .05). The LMFA and MFA groups showed significantly superior stiffness compared with the Con and MMFA groups (all P < .01). At 8 weeks, superior failure load and stiffness were observed in the LMFA group compared with the control group (all P < .05). Histologic examination revealed that the LMFA group had superior collagen composition and tendon-to-bone maturation at the interface at 4 and 8 weeks compared with the Con group (all P < .05). CONCLUSION: Lateralized microfracture at the greater tuberosity improved the histologic quality of repair tissue and biomechanical strength at the tendon-to-bone insertion after rotator cuff repair in a rat model. CLINICAL RELEVANCE: Microfracture lateral to the footprint area might be a better way to enhance rotator cuff healing clinically.

Synthesis of α-Difluoromethylene Ethers via Photoredox-Induced Hyperconjugative Ring Opening of gem-Difluorocyclopropanes.

Fluorinated compounds have found widespread applications in pharmaceuticals, agrochemicals, and materials science. Precise construction of α-difluoromethylene ether (CF2-O) moiety in organic molecules is of high demand. Herein, a visible light-promoted reaction protocol for the synthesis of α-difluoromethylene ether from gem-difluorocyclopropane is described. The key ring-opening step is induced by hyperconjugative interaction of cyclopropane with photo-oxidized aromatic rings. This reaction is easy scale-up, and the products bearing a synthetic handle enable their further manipulation.

Escape from self: Stress increase consumers' preference for experiences over material possessions.

Introduction: Considering the theory of self-escape, this research systematically investigates the effect of stress on consumers' preference for experiences vs. material possessions. Methods: We conducted one survey and two experiments to demonstrate the effect of stress on individuals' relative preference for experiential vs. material consumption and its psychological mechanism. Results: The findings of the three studies revealed that stress increases consumers' preference for experiences over material possessions. Additionally, self-escape motivation plays a mediating role between stress and preference for experiential consumption (vs. material consumption). Stress as a self-threat triggers individuals' motivation to escape from negative self-concept, and experiences can help individuals temporarily escape from negative self-recognition and provide more leisure value than material possessions. Therefore, individuals increase their consumption preference for experiences. Furthermore, we observed that the type of experiences plays a moderating role between stress and preference for experiential consumption (vs. material consumption). Specifically, compared with low cognitive resource demanding experiences, the effect of stress on experiential consumption disappears when experiences have a high demand for cognitive resources. Discussion: These findings extend the research on stress, experiential consumption and material consumption and provide significant advice for public mental health.

Save for Safe: Effect of COVID-19 Pandemic on Consumers' Saving and Spending Behavior in China.

In public health emergencies, people are more willing to save money rather than spending it, which is not conductive to economic development and recovery. Due to the absence of relevant research, the internal logic of this phenomenon is not clear. In the context of the COVID-19 pandemic, this study systematically explored whether and why public health emergencies stimulate consumers' preference for saving (vs. spending). We conducted two online surveys and used methods including stepwise regression analysis and bootstrapping to test the hypotheses. The first survey, with 1,511 participants from China in February 2020, indicates that the severity of emergencies has a significant positive impact on the populations' willingness to save (vs. spend). Risk perception plays a mediating role between the severity of emergencies and consumers' saving (vs. spending) willingness. Materialism plays a moderating role between risk perception and an individual's saving (vs. spending) willingness, individuals who are more materialistic have a lower saving (vs. spending) willingness when they perceive the risks of the pandemic. To verify the duration of the above effects, we conducted a follow-up survey consisted of 466 instances in August 2020. It is noteworthy that the above effects are not significant during the post-pandemic period. Thus, spending behavior in public health emergencies can be motived by reducing risk perception and increasing materialism. These findings can provide a valuable inspiration for public health, crisis management, and economic recovery during public health emergencies.

Copper-catalyzed aerobic decarboxylative sulfonylation of cinnamic acids with sodium sulfinates: stereospecific synthesis of (E)-alkenyl sulfones.

A copper-catalyzed aerobic decarboxylative sulfonylation of alkenyl carboxylic acids with sodium sulfinates is developed. This study offers a new and expedient strategy for stereoselective synthesis of (E)-alkenyl sulfones that are widely present in biologically active natural products and therapeutic agents. Moreover, the transformation is proposed to proceed via a radical process and exhibits a broad substrate scope and good functional group tolerance.