Due to the limited self‐repairing capacity after peripheral nerve injuries (PNI), artificial nerve conduits are widely applied to facilitate neural regeneration. Exogenous electrical stimulation (ES) that is carried out by the conductive conduit regulates the biological behavior of Schwann cells (SCs). Meanwhile, a longitudinal surface structure counts to guide axonal growth to accelerate the end‐to‐end connection. Currently, there are no conduits equipped with both electrical conduction and axon‐guiding surface structure. Herein, a biodegradable, conductive poly(l‐lactide‐co‐caprolactone)/graphene (PLCL/GN) composite conduit is designed. The conduit with 20.96 ± 1.26 MPa tensile strength has a micropatterned surface of 20 µm groove fabricated by microimprint technology and self‐assembled polydopamine (PDA). In vitro evaluation shows that the conduits with ES effectively stimulate the directional cell migration, adhesion, and elongation, and enhance neuronal expression of SCs. The rat sciatic nerve crush model demonstrates that the conductive micropatterned conduit with ES promotes the growth of myelin sheath, faster nerve regeneration, and 20‐fold functional recovery in vivo. These discoveries prove that the PLCL(G)/PDA/GN composite conduit is a promising tool for PNI treatment by providing the functional integration of physical guidance, biomimetic biological regulation, and bioelectrical stimulation, which inspires a novel therapeutic approach for nerve regeneration in the future.

Introduction Elderly patients are the most affected and vulnerable to COVID-19 and effective therapeutic interventions are urgently required. We clarified the safety and efficacy of Paxlovid in the treatment of elderly patients with coronavirus disease 2019 (COVID-19). Methods Patients aged over 60 years and with mild to moderate COVID-19 were admitted to the Zhongshan Hospital MinHang MeiLong Branch, Fudan University and received either Paxlovid treatment or only conventional therapy, between April 1 and May 31, 2022. Viral shedding time, duration of hospital stay, disease progression, and adverse events were analyzed, and multivariate Cox regression analysis was performed to detect the independent high-risk factors for COVID-19 progression in the patients. Results A total of 163 (82 and 81 in the treatment and control groups, respectively) patients had a median age of 82 (71–89) years, and 89.0% had at least one concomitant disease. The duration of hospitalization reduced from 15 to 13 days, and viral shedding time reduced from 20 to 16.5 days after Paxlovid treatment. The differences of these two variables between the groups were significant ( p < 0.01). Moreover, no serious adverse events or obvious changes in laboratory test results were observed in patients treated with Paxlovid. One patient (1.2%) treated with Paxlovid experienced rebound 56 days after negative measurement. Multivariate analysis showed that Paxlovid therapy, age, hemoglobin, and nucleic acid Ct values at admission were independent risk factors for hospitalization within 14 days, and the differences were significant ( p < 0.01). Conclusion The use of Paxlovid in elderly patients may promote recovery from COVID-19 and reduce the viral load without adverse events. Clinical trial registration www.ClinicalTrials.gov , ID: ChiCTR2200066990. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-023-00760-x.

Background. Peripheral nerve injury (PNI) is one of the most debilitating injuries, but therapies for PNI are still far from satisfactory. Pyroptosis, a recently identified form of cell death, has been demonstrated to participate in different diseases. However, the role of pyroptosis of Schwann cells in PNI remains unclear. Methods. We established a rat PNI model, and western blotting, transmission electron microscopy, and immunofluorescence staining were used to confirm pyroptosis of Schwann cells in PNI in vivo. In vitro, pyroptosis of Schwann cells was induced by lipopolysaccharides (LPS)+adenosine triphosphate disodium (ATP). An irreversible inhibitor of pyroptosis, acetyl (Ac)-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-cmk), was used to attenuate Schwann cell pyroptosis. Moreover, the influence of pyroptotic Schwann cells on the function of dorsal root ganglion neurons (DRGns) was analyzed by a coculture system. Finally, the rat PNI model was intraperitoneally treated with Ac-YVAD-cmk to observe the effect of pyroptosis on nerve regeneration and motor function. Results. Schwann cell pyroptosis was notably observed in the injured sciatic nerve. LPS+ATP treatment effectively induced Schwann cell pyroptosis, which was largely attenuated by Ac-YVAD-cmk. Additionally, pyroptotic Schwann cells inhibited the function of DRGns by secreting inflammatory factors. A decrease in pyroptosis in Schwann cells promoted regeneration of the sciatic nerve and recovery of motor function in rats. Conclusion. Given the role of Schwann cell pyroptosis in PNI progression, inhibition of Schwann cell pyroptosis might be a potential therapeutic strategy for PNI in the future.