Background Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were mainly based on information from adult populations. Limited data are available for children with COVID-19, especially for infected infants. Methods We report a 55-day-old case with COVID-19 confirmed in China and describe the identification, diagnosis, clinical course, and treatment of the patient, including the disease progression from day 7 to day 11 of illness. Results This case highlights that children with COVID-19 can also present with multiple organ damage and rapid disease changes. Conclusions When managing such infant patients with COVID-19, frequent and careful clinical monitoring is essential.

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Calcineurin inhibitors, such as tacrolimus (FK506) and cyclosporine, are widely used as standard immunosuppressants in organ transplantation recipients. However, these drugs can cause severe pain in patients, commonly referred to as calcineurin inhibitor-induced pain syndrome (CIPS). Although calcineurin inhibition increases NMDAR activity in the spinal cord, the underlying mechanism remains enigmatic. Using an animal model of CIPS, we found that systemic administration of FK506 in male and female mice significantly increased the amount of a2d-1-GluN1 complexes in the spinal cord and the level of a2d-1-bound GluN1 proteins in spinal synaptosomes. Treatment with FK506 significantly increased the frequency of mEPSCs and the amplitudes of monosynaptic EPSCs evoked from the dorsal root and puff NMDAR currents in spinal dorsal horn neurons. Inhibiting a2d-1 with gabapentin or disrupting the a2d-1-NMDAR interaction with a2d-1Tat peptide completely reversed the effects of FK506. In a2d-1 gene KO mice, treatment with FK506 failed to increase the frequency of NMDARmediated mEPSCs and the amplitudes of evoked EPSCs and puff NMDAR currents in spinal dorsal horn neurons. Furthermore, systemic administration of gabapentin or intrathecal injection of a2d-1Tat peptide reversed thermal and mechanical hypersensitivity in FK506-treated mice. In addition, genetically deleting GluN1 in dorsal root ganglion neurons or a2d-1 genetic KO similarly attenuated FK506-induced thermal and mechanical hypersensitivity. Together, our findings indicate that a2d-1-bound NMDARs mediate calcineurin inhibitor-induced tonic activation of presynaptic and postsynaptic NMDARs at the spinal cord level and that presynaptic NMDARs play a prominent role in the development of CIPS.

We sought to evaluate whether preoperative anemia was an important determinant of survival in gastric cancer (GC). A single institution cohort of 2163 GC patients who underwent curative resection were retrospectively analyzed. Anemia was defined as a preoperative hemoglobin level <120 g/L in males and <110 g/L in females. Overall survival (OS) was analyzed using the Kaplan–Meier method, and a multivariate Cox proportional hazards model was performed to identify the independent prognostic factor. Anemic patients had a poorer OS compared with nonanemic patients after resection for tumor–nodes–metastasis (TNM) stage III tumors (5‐year OS rate: 32.2% vs. 45.7%, P < 0.001) but not stage I (P  =  0.480) or stage II (P  =  0.917) tumors. Multivariate analysis revealed that preoperative anemia was an independent prognostic factor in TNM stage III (hazard ratio [HR], 1.771; 95% CI, 1.040–3.015; P = 0.035). In a stage‐stratified analysis, preoperative anemia was still independently associated with OS in TNM stages IIIa through IIIc (P < 0.001, P = 0.075, and P = 0.012, respectively), though the association was only marginal in stage IIIb. Of note, preoperative mild anemia had a similar prognostic value in TNM stage III GC. Furthermore, preoperative anemia was significantly associated with more perioperative transfusions, postoperative complications and several nutritional‐based indices, including the prognostic nutritional index (PNI), preoperative weight loss and performance status (all P < 0.05). Preoperative anemia, even mild anemia, was an important predictor of postoperative survival for TNM stage III GC.

N-methyl-D-aspartate receptors (NMDARs) are important for synaptic plasticity associated with many physiological functions and neurologic disorders. Protein kinase C (PKC) activation increases the phosphorylation and activity of NMDARs, and a2d-1 is a critical NMDAR-interacting protein and controls synaptic trafficking of NMDARs. In this study, we determined the relative roles of PKC and a2d-1 in the control of NMDAR activity. We found that a2d-1 coexpression significantly increased NMDAR activity in HEK293 cells transfected with GluN1/GluN2A or GluN1/GluN2B. PKC activation with phorbol 12-myristate 13-acetate (PMA) increased receptor activity only in cells coexpressing GluN1/GluN2A and a2d-1. Remarkably, PKC inhibition with Gӧ6983 abolished a2d-1-coexpression-induced potentiation of NMDAR activity in cells transfected with GluN1/ GluN2A or GluN1/GluN2B. Treatment with PMA increased the a2d-1-GluN1 interaction and promoted a2d-1 and GluN1 cell surface trafficking. PMA also significantly increased NMDAR activity of spinal dorsal horn neurons and the amount of a2d-1-bound GluN1 protein complexes in spinal cord synaptosomes in wild-type mice, but not in a2d-1 knockout mice. Furthermore, inhibiting a2d-1 with pregabalin or disrupting the a2d-1-NMDAR interaction with the a2d-1 C-terminus peptide abolished the potentiating effect of PMA on NMDAR activity. Additionally, using quantitative phosphoproteomics and mutagenesis analyses, we identified S929 on GluN2A and S1413 (S1415 in humans) on GluN2B as the phosphorylation sites responsible for NMDAR potentiation by PKC and a2d-1. Together, our findings demonstrate the interdependence of a2d-1 and PKC phosphorylation in regulating NMDAR trafficking and activity. The phosphorylation-dependent, dynamic a2d-1-NMDAR interaction constitutes an important molecular mechanism of synaptic plasticity.