Myelin oligodendrocyte glycoprotein-associated transverse myelitis after SARS-CoV-2 infection: A case report.

BACKGROUND: Cases of myelin oligodendrocyte glycoprotein (MOG) antibody-related disease have a history of coronavirus disease 2019 infection or its vaccination before disease onset. Severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection has been considered to be a trigger of central nervous system autoimmune diseases. CASE SUMMARY: Here we report a 20-year male with MOG-associated transverse myelitis after a SARS-CoV-2 infection. The patient received a near-complete recovery after standard immunological treatments. CONCLUSION: Attention should be paid to the evaluation of typical or atypical neurological symptoms that may be triggered by SARS-CoV-2 infection.

Correlation between right-to-left shunt and sudden sensorineural hearing loss: protocol for a case-control study.

BACKGROUND AND PURPOSE: Sudden sensorineural hearing loss (SSNHL) is a neurological and otolaryngological emergency during which rapid diagnosis and early treatment are of great importance. Clinical experience indicates that a considerable number of patients with SSNHL have concurrent right-to-left shunt (RLS). With limited reports, the association between SSNHL and RLS is yet unclear and there is a need for large observational studies to explore their latent relationship. METHODS AND ANALYSIS: This proposed study is a prospective, observational case-control study. A total of 194 eligible participants matched in age and sex will be divided equally into two groups: 97 patients with SSNHL included in the case group and 97 individuals without SSNHL in the control group. Medical evaluations, including clinical characteristics, laboratory examination, audiological examination and ultrasonography examination, will be performed in all subjects. The primary outcome of the study is the difference in RLS rates between the groups. Differences in patent foramen ovale rates and other measured variables will be further assessed. A conditional logistic regression as a correlation analysis will be used to evaluate the relationship between RLS and SSNHL. DISCUSSION: This study may provide evidence on the correlation between RLS and SSNHL in order to enrich the aetiology of SSNHL. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethics Committee of Peking University Shenzhen Hospital. A written informed consent form will be signed and dated by the participants and the researchers before the study begins. The results will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2200064067.

The correlation between medial pattern of intracranial arterial calcification and white matter hyperintensities.

BACKGROUND AND AIMS: Despite reported correlations between intracranial arterial calcification (IAC) and white matter hyperintensities (WMH), little is known about the relationship between IAC pattern and WMH. By differentiating intimal and medial IAC, we aimed to investigate the relationship between IAC pattern and WMH. METHODS: Consecutive acute stroke patients were included. IAC pattern was categorized as intimal or medial on plain brain CT. The number of cerebral arteries involved by IAC for each patient was recorded. IAC severity was defined as focal or diffuse. On brain MRI, the burden of WMH was visually graded and classified as absent mild, moderate and severe. Multiple logistic regression was performed to examine the relationship between IAC and WMH. RESULTS: Among 265 patients, intimal IAC was detected in 54.7% patients and medial IAC in 48.5% patients. Diffuse IAC was present in 27.9% patients, all of which were medial. WMH was found in 75.5% patients, including 39.6% patients with mild WMH, 26.0% with moderate WMH, and 9.8% with severe WMH. The severity of medial IAC was correlated with WMH occurrence (p < 0.001). Chi-square linear trend suggested the number of arteries involved by medial IAC (p < 0.001) and the severity of medial IAC (p < 0.001) were correlated with WMH burden. Multiple ordinal logistic regression demonstrated a positive correlation of WMH burden with the number of arteries involved by medial IAC (p < 0.001) and the severity of medial IAC (p < 0.001). CONCLUSIONS: Medial IAC was correlated with WMH. The dose-effect relationship between medial IAC and WMH suggests underlying shared mechanisms of intracranial large artery disease and small vessel disease.

Cardiocerebrovascular risk in sensorineural hearing loss: results from the National Health and Nutrition Examination Survey 2015 to 2018.

Objective: This study aims to determine whether the risks of cardiocerebrovascular disease are relevant to sensorineural hearing loss (SNHL) based on a national database. Methods: A total of 1,321 participants aged from 18 to 69 with complete data including medical history and audiometry from the NHANES database (2015-2018) were analyzed. All included participants had available hearing data and the average thresholds of the hearing data were measured and calculated as low-frequency pure-tone average (LFPTA; 500, 1,000, and 2,000 Hz) and high-frequency pure-tone average (HFPTA; 3,000, 4,000, 6,000, and 8,000 kHz). SNHL was defined as an average pure tone of more than or equal to 20 dB in at least one better ear. Multivariable models to assess the association between cardiocerebrovascular risks and SNHL were used in this study. Results: The prevalence of stroke was 1.6% in individuals with SNHL and 0.4% in individuals without SNHL (p = 0.023). A higher cardiovascular risk score was observed in SNHL patients compared to participants without SNHL (1.58 vs. 0.90, p < 0.001). Stroke was associated with a 3.67-fold increase in the risk of SNHL (95% CI: 1.12-12.00, p = 0.032) in univariable logistic regression, and the association (OR = 4.22, 95%CI = 1.28-13.93, p = 0.020) remained significant after adjusting for several covariates. Multivariable logistic regression models indicated a positive correlation between cardiovascular risk and SNHL (OR = 1.66, 95% CI = 1.40-1.96, p < 0.001), but no significant relationship was shown with all covariates adjusted. However, significant associations were found between SNHL and both age and sex in both univariable and multivariable logistic regression models. Conclusion: Our findings suggested that a higher cardiocerebrovascular risk burden was associated with an increased risk of SNHL, and the relationship may be influenced by age and sex. Future longitudinal studies are needed to investigate the mechanistic and pathologic vascular hypothesis of SNHL.

The correlation between intracranial arterial calcification and the outcome of reperfusion therapy.

OBJECTIVE: Intracranial arterial calcification (IAC) is a risk factor of ischemic stroke. However, the relationship between IAC patterns and clinical outcome of ischemic stroke remains controversial. We aimed to investigate the correlation between IAC patterns and the effects of reperfusion therapy among acute stroke patients. METHODS: Consecutive acute ischemic stroke patients who underwent reperfusion therapy were included. IAC was categorized as intimal or medial. Based on its involvement, IAC was further classified as diffuse or focal. Neurologic dysfunction was assessed by the National Institute of Health stroke scale (NIHSS). Clinical outcome including favorable neurologic outcome (FNO) and early neurologic deterioration (END) were assessed. RESULTS: Of 130 patients, 117 had IAC. Intimal IAC was identified in 74.6% of patients and medial IAC was present in 64.6% of patients. Diffuse IAC was present in 31.5% of patients. All diffuse IACs were medial pattern. Diffuse IAC was associated with higher baseline NIHSS (p = 0.011) and less FNO (p = 0.047). Compared with patients with focal or single diffuse IAC, patients with multiple diffuse IAC had higher baseline NIHSS (p = 0.002) and less FNO (p = 0.024). Multivariable linear regression (p < 0.001) and logistic regression (p = 0.027) suggested that multiple diffuse IAC was associated with higher baseline NIHSS and less FNO. No significant association was found between END and different IAC patterns. INTERPRETATION: Multiple diffuse medial IAC may predict severer neurologic dysfunction and less favorable neurologic outcome after reperfusion therapy in acute stroke patients.

Identification of hub genes and pathophysiological mechanism related to acute unilateral vestibulopathy by integrated bioinformatics analysis.

Background: Although many pathological mechanisms and etiological hypotheses of acute unilateral vestibulopathy (AUVP) have been reported, but the actual etiology remains to be elucidated. Objective: This study was based on comprehensive bioinformatics to identify the critical genes of AUVP and explore its pathological mechanism. Methods: Gene expression profiles of AUVP and normal samples were collected from GSE146230 datasets of the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was constructed, and the WGCNA R-package extracted significant modules. The limma R-package was applied to identify differentially expressed genes (DEGs). The common genes of practical modules and DEGs were screened for GO and KEGG pathways analysis. The protein-protein interaction (PPI) layout and hub genes validation was created by Cytoscape software using the link from the STRING database. The functions of hub genes were predicted through the CTD (comparative genetics database). Results: A total of 332 common genes were screened from practical modules and DEGs. Functional enrichment analysis revealed that these genes were predominantly associated with inflammation and infection. After construction of PPI, expressions of hub genes, and drawing ROC curves, LILRB2, FPR1, AQP9, and LILRA1 are highly expressed in AUVP (p < 0.05) and have a certain diagnostic efficacy for AUVP (AUC > 0.7), so they were selected as hub genes. The functions of hub genes suggested that the occurrence of AUVP may be related to inflammation, necrosis, hepatomegaly, and other conditions in CTD. Conclusion: LILRB2, FPR1, AQP9, and LILRA1 may play essential roles in developing AUVP, providing new ideas for diagnosing and treating AUVP.

Effects of freeze-thaw cycles on the texture of Nanguo pear.

Freezing is a way to preserve the quality of fruit for a long time. Nanguo pear stored at low temperature is prone to browning and lignification. In this study, freeze-thaw cycles were used to simulate the temperature fluctuation in the process, storage, and transportation. The texture properties were taken as the research focus to analyze the lignification phenomenon of Nanguo pear under freeze-thaw cycles. The results showed that freeze-thaw treatment significantly reduced the firmness and propectin content of Nanguo pear, increased the content of stone cells in the fruit, but also destroyed the size of stone cells in the fruit. However, with the increase of freezing-thawing cycles, the content of lignin, stone cell content, and PAL activity increased significantly, while the content of chlorogenic acid increased first and then decreased. These results are helpful to further understand the correlation between texture change with fruit firmness and formation mechanism of stone cells during freeze-thaw cycles of Nanguo pear.

Novel Ferrocene Derivatives Induce Apoptosis through Mitochondria-Dependent and Cell Cycle Arrest via PI3K/Akt/mTOR Signaling Pathway in T Cell Acute Lymphoblastic Leukemia.

T cell acute lymphoblastic leukemia (T-ALL) is one of the most common causes of death in pediatric malignancies. However, the clinical chemotherapy for T-ALL has been limited by numerous side effects, emphasizing that novel anti-T-ALL drugs are urgently needed. Herein, a series of 2-acyl-1-dimethylaminomethyl-ferrocenes for cancer therapy have been evaluated. Among them, F1 and F3 exhibited potent cytotoxicity against T-ALL cell lines, especially Jurkat cells, with low cytotoxicity for normal cells. Further mechanistic studies revealed that F1 and F3 could induce apoptosis in Jurkat cells by destructing mitochondrial membrane, enhancing reactive oxygen species (ROS) generation, decreasing the Bcl-2/Bax ratio, releasing Cytochrome c, and increasing the expression of Cleaved Caspase-9/-3 and Cleaved PARP. Additionally, F1 and F3 could suppress cell proliferation and arrest the cell cycle at G0/G1 phase through the PI3K/Akt/mTOR signaling pathway by down-regulating the expression of CDK6, Cyclin D1, p-Akt, p-GSK-3ß, p-mTOR, p-p70 S6K, and up-regulating the expression of P21 and P27, which would also be a possible mechanism. Consequently, ferrocene derivatives F1 and F3 could induce apoptosis through a mitochondria-dependent pathway mediated by ROS, and cell cycle arrest at G0/G1 phase via the PI3K/Akt/mTOR signaling pathway in Jurkat cells. The present study provided fundamental insights into the clinical application of F1 and F3 for the treatment of T-ALL.

Novel Ferrocene Derivatives Induce G0/G1 Cell Cycle Arrest and Apoptosis through the Mitochondrial Pathway in Human Hepatocellular Carcinoma.

In this study, detailed information on hepatocellular carcinoma (HCC) cells (HepG-2, SMMC-7721, and HuH-7) and normal human liver cell L02 treated by ferrocene derivatives (compounds 1, 2 and 3) is provided. The cell viability assay showed that compound 1 presented the most potent and selective anti-HCC activity. Further mechanism study indicated that the proliferation inhibition effect of compound 1 was associated with the cycle arrest at the G0/G1 phase and downregulation of cyclin D1/CDK4. Moreover, compound 1 could induce apoptosis in HCC cells by loss of mitochondrial membrane potential (ΔΨm), accumulation of reactive oxygen species (ROS), decrease in Bcl-2, increase in BAX and Bad, translocation of Cytochrome c, activation of Caspase-9, -3, and cleavage of PARP. These results indicated that compound 1 would be a promising candidate against HCC through G0/G1 cell cycle arrest-related proliferation inhibition and mitochondrial pathway-dependent apoptosis.

Knockdown of FBXO39 inhibits proliferation and promotes apoptosis of human osteosarcoma U-2OS cells.

F-box proteins are essential components of the Skp-cullin-F-box complex (a type of E3 ubiquitin ligase), and participate in cell cycle and immune responses through the ubiquitin proteasome system. F-box protein 39 (FBXO39) belongs to the F-box family, which has been reported to be associated with cancer oncogenesis and progression. The present study aimed to investigate the role of FBXO39 in osteosarcoma (OS) cell proliferation and apoptosis in vitro. It was demonstrated that U-2OS cells exhibited high expression of FBXO39 compared with HOS and SaOS-2 osteosarcoma cells. Thus, knockdown of FBXO39 was performed using lentivirus-mediated short hairpin RNA (shRNA) transfection to validate the effect of FBXO39 in U-2OS cells. Western blotting and RT-qPCR analysis were used to confirm the efficiency of infection by analyzing the expression level of FBXO39. Using Celigo-based cell counting and MTT assays, it was demonstrated that FBXO39 knockdown significantly reduced the rate of cell proliferation compared with control. Caspase 3/7 activity assays and fluorescence-activated cell sorting confirmed the induction of apoptosis in U-2OS cells following FBXO39 knockdown. In conclusion, it was demonstrated that FBXO39 knockdown may significantly inhibit proliferation and promote apoptosis of U-2OS cells. Thus, FBXO39 may serve an important role in OS progression.

Using microRNAs as Novel Predictors of Urologic Cancer Survival: An Integrated Analysis.

BACKGROUND: MicroRNAs(miRNAs) are involved in the formation, maintenance, and metastasis of urologic cancer. Here, we aim to gather and evaluate all of the evidence regarding the potential role of miRNAs as novel predictors of urologic cancer survival. METHODS: A systematic review was performed to identify and score all of the published studies that evaluated the prognostic effects of miRNAs in kidney (KCa), bladder (BCa) or prostate cancer (PCa). Where appropriate, the summary effects of miRNAs on urologic cancer were meta-analysed. The reliability of those results was then further validated by an integrated analysis of the TCGA cohort and miRNA panel. RESULTS: Of 151 datasets, 80 miRNAs were enrolled in this systematic review. A meta-analysis of the prognostic qualities of each miRNA identified an objective association between miRNA and prognosis. miR-21 was identified as an unfavourable miRNA with the overall survival (HR:2.699, 1.76-4.14, P < 0.001) across various prognostic events. Our further meta-analyses, integrating a parallel TCGA analysis, confirmed these partial previous results and further revealed different summary effects, such as the moderate effect of miR-21 in BCa. The refined miRNA panel (KCa-6: miR-27b, -942, -497, -144, -141 and -27a) was more capable of predicting the overall survival than was any single miRNAs included in it (HR: 3.214, 1.971-5.240, P < 0.01). CONCLUSIONS: A miRNA panel may be able to determine the prognosis of urologic tumour more effectively and compensate for the unreliability of individual miRNA in estimating prognosis. More large-scale studies are therefore required to evaluate the unbiased prognostic value of miRNAs in urologic cancer effectively.