Case report: A case of anti-glycine receptor encephalomyelitis triggered by post-transplant or COVID-19 infection?

Even though long-term immunosuppressant drugs (ISD) are employed to inhibit immune system activity, enhancing graft functionality and patient survival in solid organ transplantation (SOT), these transplants often lead to immune complications, with post-transplant autoimmune diseases of the central nervous system (CNS) being uncommon. Here, we detail the case of a 66-year-old woman who underwent a renal transplantation 8 months prior, who was admitted with subacute onset of encephalomyelitis, accompanied by headaches, paraplegia, weakness, vomiting, and abdominal pain, with a positive COVID-19 nasopharyngeal swab test 1 month before admission. MRI scans of the brain revealed multiple lesions in the white matter of the bilateral deep frontal lobe, the left temporal lobe and insula lobe. Additionally, there were multiple short segment lesions in the spinal cord and subdural hematoma at T1, T6-T7 posterior. The serum revealed a positive result for GlyR-IgG. Following the administration of corticosteroid and intravenous immunoglobulin, there was a significant improvement in the patient's symptoms within 2 weeks, and her brain MRI showed a reduction in the lesion. Despite its rarity, we believe this to be the inaugural documentation of anti-GlyR encephalomyelitis occurring during renal transplantation. A full panel of antibodies for autoimmune encephalomyelitis is the key leading to the diagnosis.

Radical footprinting and regularity revealing during the pyrolysis of technical lignins.

Revealing radical-mediated reactions is conducive to illustrate lignin pyrolysis and achieve subsequent regulation. Three technical lignins (hot-water-extracted lignin, kraft lignin, and soda lignin) were selected in this study and pyrolyzed from 400 °C to 700 °C, and their pyrolysis radicals in both chars and bio-oils were monitored with the electron paramagnetic resonance spectrometer. Results showed that spin concentrations of char radicals had a volcanic trend against the pyrolysis temperature, and reached the maximum values at 550-600 °C. However, the contents of bio-oil radicals were low during pyrolysis at low and medium temperature, but their spin concentrations exploded abruptly over 600-650 °C. Meanwhile, the bio-oil yields were found to drop after 550-600 °C, and the three inflection temperatures for char radicals, bio-oil radicals, and bio-oil yields were perfectly matched. These findings systematically elucidated the radical regularity in technical lignin pyrolysis and fundamentally contributed to the development of radical-mediated lignin pyrolysis mechanisms.

Elucidating radical-mediated pyrolysis behaviors of preoxidized lignins.

Effect of lignin preoxidation on subsequent radical-mediated pyrolysis was discussed in this study. Technical hot-water-extracted lignin was preoxidized by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in diverse degrees and pyrolyzed under different temperatures. Characterizations indicated that preoxidation increased lignin oxygen contents and converted α-hydroxyls to α-carbonyls. These structural modifications caused by preoxidation reduced the thermal stability and pyrolysis reactivity of lignin, shifting lignin thermal decomposition to the low temperature region and inhibiting lignin pyrolysis into bio-oil fractions. However, recognition of species and yields of specific compounds via analytical pyrolysis declared that although preoxidation reduced product yields, it did not alter the reaction pathways. The fixed bed experiments proved the above findings and gave the gas compositions, mainly CO2 derived through decarbonylation. Both radicals in chars and bio-oils were monitored, and char radical concentrations were proportional to the preoxidation degrees. This work sorted out the performances of lignin pyrolysis after preoxidation and determined their negative effects.

Unmasking radical-mediated lignin pyrolysis after benzyl hydroxyl shielding.

Whether lignin benzyl hydroxyl shielding could promote its pyrolysis to phenolic compounds was investigated in this paper. Lignin benzyl hydroxyl was first preoxidized by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and stabilized by propionaldehyde respectively, then pyrolysis was conducted with milled wood lignin as a control. Organic stable radicals in pyrolytic chars were further detected to reveal lignin pyrolysis chemistry. Results showed that benzyl hydroxyl shielding process weakened lignin thermal stability, and decreased liquid yields regardless of the frequency of lignin ß-O-4 linkages. In addition, char yield grew after benzyl hydroxyl shielding. Radical concentration was inversely proportional to ß-O-4 content which indicated the non-negligible impact of shielded benzyl hydroxyl on lignin pyrolysis. Furthermore, gases from propionaldehyde stabilized lignin quenched its radicals. This work confirmed that lignin ß-O-4 linkages and shielded benzyl hydroxyl both played the great role in radical-mediated pyrolysis, but the enhancement of liquid products could not be achieved via benzyl hydroxyl shielding.

Genetic Creutzfeldt-Jakob disease shows fatal family insomnia phenotype.

We report a case of genetic Creutzfeldt-Jakob disease (gCJD), which has a clinical phenotype that is highly similar to Fatal Family Insomnia (FFI) and has a triad of Wernicke-Korsakoff syndrome (WKs) at the developmental stage of the disease. The 51-year-old male complained of sleep disorder and imbalance who had visited five different hospitals before diagnosed. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk, and memory disturbances. The disturbances increased during the course of the disease, which led to the death of the patient 18 months after the appearance of the signs. Although the patient show negative in brain magnetic resonance imaging (MRI) and 14-3-3 protein of cerebrospinal fluid (CSF), he was finally diagnosed with gCJD disease by the human prion protein (PRNP) gene mutations.

The adenosine A2A receptor antagonist SCH58261 reduces macrophage/microglia activation and protects against experimental autoimmune encephalomyelitis in mice.

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS) affecting more than 2.5 million individuals worldwide. In the present study, myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) mice were treated with adenosine receptor A2A antagonist SCH58261 at different periods of EAE development. The administration of SCH58261 at 11-28 days post-immunization (d.p.i.) with MOG improved the neurological deficits. This time window corresponds to the therapeutic time window for MS treatment. SCH58261 significantly reduced the CNS neuroinflammation including reduced local infiltration of inflammatory cells, demyelination, and the numbers of macrophage/microglia in the spinal cord. Importantly, SCH58261 ameliorated the EAE-induced neurobehavioral deficits. By contrast, the SCH58261 treatment was ineffective when administered at the beginning of the onset of EAE (i.e., 1-10 d.p.i). The identification of the effective therapeutic window of A2A receptor antagonist provide insight into the role of A2A receptor signaling in EAE, and support SCH58261 as a candidate for the treatment of MS in human.

[CEMENTLESS TOTAL HIP ARTHROPLASTY FOR TREATMENT OF Crowe TYPE â ¢ DEVELOPMENTAL DYSPLASIA OF HIP IN ADULTS].

OBJECTIVE: To investigate the value of cementless total hip arthroplasty (THA) for the treatment of Crowe type Ⅲ developmental dysplasia of hip (DDH) in adults. METHODS: Between September 2013 and September 2015, 50 patients (51 hips) with Crowe type Ⅲ DDH were treated. There were 20 males (20 hips) and 30 females (31 hips), with the average age of 39 years (range, 19-55 years). The left side was involved in 34 cases, the right side in 15 cases, and both sides in 1 case. All patients had the symptoms of limp walking and hip pain. The disease duration was 10-47 months (mean, 26 months). The sign of "4" number test and Trendenleburg sign were positive; the Harris score was 38.9±7.1. The bilateral lower extremities discrepancy was 2.5-4.0 cm (mean, 3.3 cm) before operation. All the patients underwent cementless THA, and acetabulum by structural femoral head autograft was performed in 28 cases (28 hips). RESULTS: After operation, the incision healed by first intention. Only 2 patients (2 hips) had femoral nerve palsy, and 7 patients (7 hips) had leg swelling, which were cured after symptomatic treatment. All the patients were followed up 6-18 months (mean, 10 months). The sign of limp walking was improved after operation, hip pain was relieved in 46 patients (46 hips) and only 4 patients (5 hips) still had mild pain. The X-ray films showed bony healing at 3-6 months (mean, 5 months) after operation. At last follow-up, the patients had equal limb length with the discrepancy less than 1 cm (mean, 0.4 cm). At last follow-up, the Harris score was significantly increased to 91.2±2.8 (t=-79.77, P=0.00). CONCLUSIONS: The cementless THA is an effective method to treat Crowe type Ⅲ DDH in adults.

2-BFI ameliorates EAE-induced mouse spinal cord damage: effective therapeutic time window and possible mechanisms.

Our previous studies showed that ligands to type 2 imidazoline receptors (I2R), including 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) and Idazoxan, were effective in reducing spinal cord inflammation caused by experimental autoimmune encephalomyelitis (EAE). In the present study, we determined the effective therapeutic time window of 2-BFI and found that administration of 2-BFI in mice before the appearance of ascending flaccid paralysis (1-10 days post immunization), but not during the period when neurological deficits occurred (11-20 days post immunization), significantly ameliorated EAE-induced neurobehavioral deficits, reduced the infiltration of inflammatory cells into the spinal cord, and reduced the level of demyelination. More interestingly, giving 2-BFI during 1-10 days post immunization selectively suppressed IL-17 levels in the peripheral blood, which strongly suggests that IL-17 may be a good early marker to indicate EAE progression and that 2-BFI may target CD4⁺ T lymphocytes, especially Th17 cells to reduce IL-17 expression. Collectively, these studies led us to envisage that 2-BFI can be a useful drug to treat multiple sclerosis (MS) when used in combination with an early indicator of MS progression, such as IL-17.