Autoimmune glial fibrillary acidic protein astrocytopathy mimicking acute disseminated encephalomyelitis: A case report

Introduction:Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an increasingly recognized type of steroid-responsive autoimmune disease of the nervous system. Defined in 2016, it is associated with the presence of anti-GFAP immunoglobulinG in the serum or cerebrospinal fluid (CSF) of affected patients.Patient characteristics:Herein, we report a case of acute neurological symptoms, including headache, fever, confusion, and paralysis of the lower extremities. CSF analysis revealed lymphocytic pleocytosis and elevated protein levels, indicating acute disseminated encephalomyelitis, and the patient was given immunotherapy. Cranial magnetic resonance imaging showed multifocal T2/fluid-attenuated inversion recovery hyperintense signal changes in the periventricular white matter, and electromyography testing showed changes consistent with severe sensorimotor neuropathy, indicating the involvement of the brain and peripheral nerves.Diagnoses:Finally, a diagnosis of autoimmune GFAP astrocytopathy was confirmed due to the presence of GFAP-immunoglobulinG in the patient''s CSF.Interventions:The patient was treated with one course of intravenous immunoglobulin therapy, then followed with intravenous methylprednisolone (1.0 g/d for 3 days) and oral prednisolone.Outcomes:At 1 week after intravenous immunoglobulin therapy, his level of consciousness improved. However, flaccid paralysis persisted without substantial improvement.Conclusion:In conclusion, the provision of an accurate early diagnosis and appropriate treatment are crucial for improving the prognosis of patients with autoimmune GFAP astrocytopathy. Further, this case highlights the importance of recognizing the role of peripheral nerve involvement in GFAP autoimmunity.     

Fluoxetine Regulates Neurogenesis In Vitro Through Modulation of GSK-3β/β-Catenin Signaling

Background:

It is generally accepted that chronic treatment with antidepressants increases hippocampal neurogenesis, but the molecular mechanisms underlying their effects are unknown. Recently, glycogen synthase kinase-3 beta (GSK-3β)/β-catenin signaling was shown to be involved in the mechanism of how antidepressants might influence hippocampal neurogenesis.

Methods:

The aim of this study was to determine whether GSK-3β/β-catenin signaling is involved in the alteration of neurogenesis as a result of treatment with fluoxetine, a selective serotonin reuptake inhibitor. The mechanisms involved in fluoxetine’s regulation of GSK-3β/β-catenin signaling pathway were also examined.

Results:

Our results demonstrated that fluoxetine increased the proliferation of embryonic neural precursor cells (NPCs) by up-regulating the phosphorylation of Ser9 on GSK-3β and increasing the level of nuclear β-catenin. The overexpression of a stabilized β-catenin protein (ΔN89 β-catenin) significantly increased NPC proliferation, while inhibition of β-catenin expression in NPCs led to a significant decrease in the proliferation and reduced the proliferative effects induced by fluoxetine. The effects of fluoxetine-induced up-regulation of both phosphorylation of Ser9 on GSK-3β and nuclear β-catenin were significantly prevented by the 5-hydroxytryptamine-1A (5-HT_1A) receptor antagonist WAY-100635.

Conclusions:

The results demonstrate that fluoxetine may increase neurogenesis via the GSK-3β/β-catenin signaling pathway that links postsynaptic 5-HT_1A receptor activation.     

Long event-free survival after anti-BCMA CAR-T cell treatment for relapsed and refractory multiple myeloma patients: Two case reports

Introduction:Chimeric antigen receptor T (CAR-T) cells targeting B-cell maturation antigen (BCMA) have been used in the treatment of relapsed and refractory multiple myeloma (RRMM). The response rate and the depth of responses induced by anti-BCMA CAR-T cells are impressive. However, despite this, remissions are not sustained, and the majority of patients eventually relapse.Patient concerns:Two patients with multiple myeloma (MM) were selected to enroll in a phase I study involving anti-BCMA CAR-T cells (ChiCTR-OPC-16009113) because they did not have the good effect after traditional treatment. One is a 48-year-old male patient who received a diagnosis of IgG lambda MM in June 2015, he has received 4 cycles of cyclophosphamide, bortezomib, and dexamethasone (CyBorD) and obtained a complete response (CR). Approximately 11 months later, the disease progressed. Subsequent treatment included regimens incorporating liposomal doxorubicin, bortezomib, and dexamethasone (3 cycles); the response was poor, and the disease kept progressing. Another 65-year-old female patient received a diagnosis of IgG lambda MM in September 2016, she has received induction therapy with 1 cycle of bortezomib and dexamethasone (VD) and 4 cycles of lenalidomide and dexamethasone, the response was poor.Diagnosis:Both patients were diagnosed with RRMM according to the International Myeloma Working Group criteria.Interventions:Both patients received infusions of anti-BCMA CAR-T cells following an induction chemotherapy regimen of cyclophosphamide and fludarabine.Outcomes:Both of them achieved a stringent CR at the 30th day with minimal residual disease-negative bone marrow by flow cytometry and serum monoclonal protein was undetectable at 4 and 10 months after cell transfusion. The CR has persisted in the 2 patients for >36 months.Conclusions:Our findings demonstrate the anti-BCMA CAR-T cell treatment is a feasible therapeutic option for patients with RRMM. Fewer early lines of treatment may be beneficial to maintain the efficacy of CAR-T cells.Trial registration:ChiCTR-OPC-16009113.     

The effect of whole-body vibration exercise on postmenopausal women with osteoporosis: A protocol for systematic review and meta-analysis

Background:Osteoporosis (OP) is an age-related disease characterized by reduced bone mass and increased bone fragility. It is more common in older people and postmenopausal women. As a new type of exercise training for OP, whole-body vibration (WBV) exercise has been proved to have a good effect on postmenopausal women with OP. It can increase bone density and improve strength and balance in postmenopausal population, which has certain clinical value, but lacks evidence-based medicine evidence. This study aims to systematically study the effectiveness of WBV exercise on postmenopausal women with OP.Methods:The English databases (PubMed, Embase, Web of Science, The Cochrane Library) and Chinese databases (China National Knowledge Network, Wanfang, Weipu, China Biomedical Database) were searched by computer. From the establishment of the database to February 2021, the randomized controlled clinical studies on WBV exercise on postmenopausal women with OP were conducted. The quality of the included studies was independently extracted by 2 researchers and literature quality was evaluated. Meta-analysis of the included studies was performed using RevMan5.3 software.Results:In this study, the efficacy and safety of WBV exercise on postmenopausal women with OP were evaluated by lumbar spine bone density, femoral neck bone density, pain, incidence of falls, incidence of fractures, and quality of life scale score, etc.Conclusion:This study will provide reliable evidences for the clinical application of WBV exercise on postmenopausal women with OP.Ethics and dissemination:Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.OSF Registration number:DOI 10.17605/OSF.IO/WPYT9     

Clinicopathologic features and clinical outcomes of intravenous leiomyomatosis of the uterus: A case series

Rationale:Intravenous leiomyomatosis (IVL) is a rare and special type of smooth muscle tumor originating in the uterus. It is classified as a benign disease according to its histological features but shows the behavioral characteristics of a malignant tumor. It is easily misdiagnosed and recurrent. The purpose of this study was to retrospectively analyze clinicopathological data of 25 cases of IVL in order to enhance clinicians’ understanding of this rare disease.Patient concerns:We screened and identified 25 cases of IVL at our hospital from October 2013 to January 2020. Five patients had tumors.Diagnoses:The diagnosis in each case was pathologically confirmed after surgical treatment.Interventions:All patients were managed surgically. Although the surgical procedures were different, the surgical approach was geared towards achieving complete excision. Three patients received hormonal therapy with gonadotropinreleasing hormone agonists after surgery.Outcomes:We retrospectively reviewed all medical records and analyzed the clinicopathologic features and clinical outcomes of this disease as well as the correlations between the clinical features and risk of recurrence. Neither the symptoms nor the preoperative imaging results were suggestive of IVL in any of the cases. Except for two patients who were lost to follow-up, twenty-three patients who were followed up are still alive. Three patients experienced a recurrence.Lessons:The clinical manifestations and ultrasound images of IVL in the early stages are not typical; thus, IVL is easily misdiagnosed as uterine leiomyoma. Radiologists, pathologists, and surgeons should have a thorough understanding of IVL and a high index of vigilance for IVL in clinical practice. Surgery should always be aimed at achieving complete tumor excision. Patients with large lesions (≥7 cm) and lesions extending to the broad ligament may have an increased risk of recurrence. Early detection, diagnosis, and treatment are very important; once the diagnosis is confirmed, regular follow-ups are crucial.     

Early prediction model for progression and prognosis of severe patients with coronavirus disease 2019

Coronavirus disease 2019 (COVID-19) has been a rampant worldwide health threat and we aimed to develop a model for early prediction of disease progression.This retrospective study included 124 adult inpatients with COVID-19 who presented with severe illness at admission and had a definite outcome (recovered or progressed to critical illness) during February 2020. Eighty-four patients were used as training cohort and 40 patients as validation cohort. Logistic regression analysis and receiver operating characteristic curve (ROC) analysis were used to develop and evaluate the prognostic prediction model.In the training cohort, the mean age was 63.4 ± 1.5 years, and male patients (48, 57%) were predominant. Forty-three (52%) recovered, and 41 (49%) progressed to critical. Decreased lymphocyte count (LC, odds ratio [OR] = 4.40, P = .026), elevated lactate dehydrogenase levels (LDH, OR = 4.24, P = .030), and high-sensitivity C-reactive protein (hsCRP, OR = 1.01, P = .025) at admission were independently associated with higher odds of deteriorated outcome. Accordingly, we developed a predictive model for disease progression based on the levels of the 3 risk factors (LC, LDH, and hsCRP) with a satisfactory performance in ROC analysis (area under the ROC curve [AUC] = 0.88, P < .001) and the best cut-off value was 0.526 with the sensitivity and specificity of 75.0% and 90.7%, respectively. Then, the model was internally validated by leave-one-out cross-validation with value of AUC 0.85 (P < .001) and externally validated in another validation cohort (26 recovered patients and 14 progressed patients) with AUC 0.84 (P < .001).We identified 3 clinical indicators of risk of progression and developed a severe COVID-19 prognostic prediction model, allowing early identification and intervention of high-risk patients being critically illness.     

Study on acupuncture improving insomnia comorbid with depression and anxiety based on rs-fMRI: A protocol for systematic review and meta-analysis

Background:Long term insomnia and low sleep quality often lead to depression, anxiety and other negative emotions, and often interact with each other. Many studies have confirmed the effectiveness of acupuncture in the treatment of insomnia comorbid with emotional disorders, but its specific mechanism needs to be further explored. Resting-state functional magnetic resonance (rsfMRI) is an important means to study the changes of brain activity. However, the results are inconsistent and lack of systematic evaluation and analysis.Methods:Nine databases will be searched, including PubMed, EMBASE, EBSCOhost-medline, Web of Science, Cochrane Library, China National Knowledge Infrastructure, VIP Database and Wan-Fang Database, Chinese Biomedical Literature Database from inception to January 2021. And screening clinical registration platform related research, in order to obtain more relevant studies. The outcomes include the change of rs-fMRI, sleep quality, depression, and anxiety. Quality assessment of the included studies will be performed according to the Cochrane Risk of Bias tool. Evidence quality will be assessed by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. RevMan software (Version 5.3) and stata13.1will be used for statistical analyses. Subgroup analysis will be performed if necessary. If the data is insufficient, qualitative synthesis will be conducted instead of quantitative synthesis.Results:This study will analyze the effect of acupuncture on the brain activity changes, improvement of sleep quality and clinical symptoms of anxiety and depression with insomnia comorbid with emotional disorders.Conclusion:This study used meta-analysis method to explore the characteristics of acupuncture on brain activity changes in insomnia comorbid with emotional disorders, so as to provide effective evidence for clarifying its pathogenesis.     

Cardiac magnetic resonance feature tracking of the right ventricle in convalescent Kawasaki disease in a large single center

BackgroundThe changes in right ventricular (RV) contractility of Kawasaki disease (KD) still remain unclear.HypothesisWe aimed to determine whether RV systolic dysfunction can be detected by cardiac magnetic resonance (CMR) feature tracking and to find its association with coronary artery lesions (aneurysm, thrombosis and stenosis).MethodsPeak systolic myocardial longitudinal, radial and circumferential strain and the strain rate (RVSL, RVSR, RVSC, RVSRL, RVSRR and RVSRC) in the global RV and three levels (basal, middle and apical) were measured in 66 patients with convalescent KD. A total of 20 controls were included. Comparisons were made with controls and among KD subgroups divided with coronary artery lesions.ResultsRVSC (−10.575% vs. −10.760%), RVSL (−18.150% vs. −18.712%) and RVSRC (−0.815/s vs. −0.924/s) were slightly lower in KD group without significant difference. All the strain and strain rate presented lowest in the basal level. In subgroup comparison, lower RVSL and RVSRL were observed in the giant coronary artery aneurysm (CAA) group; RVSR (15.844% vs. 16.897%), RVSRR (1.245/s vs. 1.322/s) and RVSRC (−0.715/s vs. −0.895/s) were lower in thrombosed group; RVSRL (−1.27/s vs. −1.503/s) were lower in stenosis group. All the comparison in subgroups did not reach significant difference. From the analysis of receiver operating characteristic curve, RVSRL had a better ability to identify KD with giant CAA and stenosis. For the identification of thrombosis, RVSRC had a better ability.ConclusionsLower strain and strain rates of RV were detected in convalescent KD. More pronounced in those with persisting coronary artery lesions.     

Identification of prognostic genes and construction of a novel gene signature in the skin melanoma based on the tumor microenvironment

Skin melanoma remains a highly prevalent and yet deadly form of cancer, with the exact degree of melanoma-associated mortality being strongly dependent upon the local tumor microenvironment. The exact composition of stromal and immune cells within this microenvironmental region has the potential to profoundly impact melanoma progression and prognosis. As such, the present study was designed with the goal of clarifying the predictive relevance of stromal and immune cell-related genes in melanoma patients through comprehensive bioinformatics analyses. We therefore analyzed melanoma sample gene expression within The Cancer Genome Atlas database and employed the ESTIMATE algorithm as a means of calculating both stromal and immune scores that were in turn used for identifying differentially expressed genes (DEGs). Subsequently, univariate analyses were used to detect DEGs associated with melanoma patient survival, and through additional functional enrichment analyses, we determined that these survival-related DEGs are largely related to inflammatory and immune responses. A prognostic signature comprised of 10 genes (IL15, CCL8, CLIC2, SAMD9L, TLR2, HLA.DQB1, IGHV1–18, RARRES3, GBP4, APOBEC3G) was generated. This 10-gene signature effectively separated melanoma patients into low- and high-risk groups based upon their survival. These low- and high-risk groups also exhibited distinct immune statuses and differing degrees of immune cell infiltration. In conclusion, our results offer novel insights into a number of microenvironment-associated genes that impact survival outcomes in melanoma patients, potentially highlighting these genes as viable therapeutic targets.