Azvudine versus paxlovid for oral treatment of COVID-19 in Chinese patients.

PURPOSE: To explore the effect of azvudine as compared to paxlovid for oral treatment of hospitalized patients with SARS-CoV-2 infection. METHODS: We analyzed data from a cohort of patients with SARS-CoV-2 infection in Shandong provincial hospital between February 15 and March 15, 2023. The primary outcome was time to sustained clinical recovery through Day 28 and secondary outcomes included the percentage of participants who died from any cause by Day 28, the average hospitilization time and expenses, the changes in liver and kidney function and adverse events. The Kaplan-Meier method and Cox regression model was used for statistical analysis. RESULTS: There was no significant difference between azvudine and paxlovid in terms of time to sustained clinical recovery (p = 0.429) and death rates (p = 0.687). As for hospitalization time and fee, no significant differences were observed between azvudine group and paxlovid group (Hospitalization time: p = 0.633; Hospitalization fee: p = 0.820). In addition, there were no significant differences in the effects of the two drugs on liver and kidney function (p > 0.05). CONCLUSION: Among adults who were hospitalised with SARS-CoV-2 infection, azvudine was noninferior to paxlovid in terms of time to sustained clinical recovery, death rates, hospitalization time and cost, with few safety concerns. TRIAL REGISTRATION: ChiCTR2300071309; Registered 11 May 2023. LEVEL OF EVIDENCE: Level III; Retrospective cohort study.

Resolvin D2 Relieving Radicular Pain is Associated with Regulation of Inflammatory Mediators, Akt/GSK-3ß Signal Pathway and GPR18.

Neuroinflammation induced by protruded nucleus pulposus (NP) has been shown to play a significant role in facilitation of radicular pain. Resolvin D2 (RvD2), a novel member of resolvin family, exhibits potent anti-inflammatory, pro-resolving and antinociceptive effects. But the effect of RvD2 in radicular pain remains unknown. The radicular pain rat models were induced by application of NP to L5 dorsal root ganglion. Each animal received intrathecal injections of vehicle or RvD2 (10 ng µl-1 or 100 ng µl-1). Mechanical thresholds were determined by measuring the paw withdrawal threshold for 7 days. The expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor-ß1 (TGF-ß1) in ipsilateral lumbar segment of rat spinal dorsal horns were measured by using ELISA and real time-PCR. Western blot was used to measure the expressions of phosphorylated Akt (p-Akt) and phosphorylated glycogen synthase kinase 3 beta (p-GSK-3ß). The expressions and distributions of RvD2 receptor, G-protein-coupled receptor 18 (GPR18), were also explored in the spinal cord of rats by using double-label immunofluorescence. RvD2 treatment caused significant reductions in the intensity of mechanical hypersensitivity and spinal expressions of TNF-α and IL-6. Meanwhile, RvD2 increased the expressions of TGF-ß1 and regulated Akt/GSK-3ß signaling. Furthermore, immunofluorescence showed that GPR18 colocalized with neurons and astrocytes in spinal cord. The results suggested that RvD2 might attenuate mechanical allodynia via regulating the expressions of inflammatory mediators and activation of Akt/GSK-3ß signal pathway. RvD2 might offer a hopeful method for radicular pain therapy.

Intrathecal Injection of Resveratrol Attenuates Burn Injury Pain by Activating Spinal Sirtuin 1.

OBJECTIVE: The present study sought to detect spinal sirtuin 1 (SIRT1) and acetylation of histone H3 (Ac-H3) expression in rats with burn injury pain (BIP model). PROCEDURES AND RESULTS: A BIP model was first established. BIP rats showed lower paw withdrawal threshold (PWT) from day 1, which persisted for 21 days following the burn injury. Spinal SIRT1/Ac-H3 expression increased following burn injury. The intrathecal use of resveratrol increased PWT and SIRT1 expression but induced down-regulation of Ac-H3 expression. We first demonstrated that the inhibition of SIRT1 significantly induced mechanical allodynia in naïve rats. The preinjection of SIRT1 inhibitor partly antagonized the analgesic effects of resveratrol in BIP rats. CONCLUSION: Inhibition of SIRT1 produces pain facilitation in the naïve rats. The expression of spinal SIRT1 increased after burn injury in the BIP model. The activation of spinal SIRT1 might mediate the resveratrol-induced analgesic effects. SUMMARY: Burn injury resulted in pain facilitationResveratrol attenuates pain facilitation induced by burn injuryIntrathecal injection of resveratrol attenuates burn injury pain by increasing spinal sirtuin 1 (SIRT1) expressionInhibition of SIRT1 by selisistat, an SIRT1 inhibitor attenuated analgesic effects of resveratrol Abbreviations used: SIRT1: Sirtuin 1, Ac-H3: Acetylation of histone H3, SD: Sprague-Dawley, EX527: Selisistat, an SIRT1 inhibitor, BIP: Burn injury pain, DMSO: Dimethyl sulfoxide, PWTs: Paw withdrawal thresholds.

Resolvin D1 Inhibits Mechanical Hypersensitivity in Sciatica by Modulating the Expression of Nuclear Factor-κB, Phospho-extracellular Signal-regulated Kinase, and Pro- and Antiinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion.

BACKGROUND: Accumulating evidence indicates that spinal inflammatory and immune responses play an important role in the process of radicular pain caused by intervertebral disk herniation. Resolvin D1 (RvD1) has been shown to have potent antiinflammatory and antinociceptive effects. The current study was undertaken to investigate the analgesic effect of RvD1 and its underlying mechanism in rat models of noncompressive lumbar disk herniation. METHODS: Rat models of noncompressive lumber disk herniation were established, and mechanical thresholds were evaluated using the von Frey test during an observation period of 21 days (n = 8/group). Intrathecal injection of vehicle or RvD1 (10 or 100 ng) was performed for three successive postoperative days. On day 7, the ipsilateral spinal dorsal horns and L5 dorsal root ganglions (DRGs) were removed to assess the expressions of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-10, and transforming growth factor-ß1 (TGF-ß1) and the activation of nuclear factor-κB (NF-κB)/p65 and phospho-extracellular signal-regulated kinase (p-ERK) signaling (n = 30/group). RESULTS: The application of nucleus pulposus to L5 DRG induced prolonged mechanical allodynia, inhibited the production of IL-10 and TGF-ß1, and up-regulated the expression of TNF-α, IL-1ß, NF-κB/p65, and p-ERK in the spinal dorsal horns and DRGs. Intrathecal injection of RvD1 showed a potent analgesic effect, inhibited the up-regulation of TNF-α and IL-1ß, increased the release of IL-10 and TGF-ß1, and attenuated the expression of NF-κB/p65 and p-ERK in a dose-dependent manner. CONCLUSIONS: The current study showed that RvD1 might alleviate neuropathic pain via regulating inflammatory mediators and NF-κB/p65 and p-ERK pathways. Its antiinflammatory and proresolution properties may offer novel therapeutic approaches for the management of neuropathic pain.