Challenges to associate early onset epilepsy with COVID-19 autoimmune encephalitis:A case

BACKGROUND Diagnosis of coronavirus disease 2019(COVID-19)-related neurological events in the pediatric population is challenging.Overlapping clinical picture of children with altered neurological state and inborn errors of metabolism,in addition to the frequency of asymptomatic COVID-19 cases,pose the main challenges for diagnosis.Diagnostic approaches to the onset post-COVID 19 subacute encephalopathy are still troublesome as seronegative autoimmune encephalitis(AIE)is reported.CASE SUMMARY A 27-mo-old boy was admitted for stormy refractory seizure of polymorphic semiology and altered mental status followed by various neuropsychiatric features that were suggestive of AIE.Brain magnetic resonance imaging and cerebrospinal fluid analysis were normal.Neither the immunological assessment,including viral serologies,antinuclear antibodies,autoimmune antibodies(NMDA,AMPA,CASPR2,LG11,GABARB,Hu,Yo,Ri,CV2,PNMA2,SOX1,Titin,amphiphysin,Recoverin),nor the metabolic assessment for lactate and pyruvate showed significant anomaly.Both positive history of COVID-19 infection and the findings of characteristic repetitive extreme delta brush played a key role in the diagnosis of COVID-19-related AIE.A remarkable improvement in the state of the child was noted after two pulse doses of intravenous Veinoglobulin and high dose of intravenous Corticosteroid.CONCLUSION Diagnostic biomarkers for AIE might aid effective treatment.

Aberrant methylation of SPARC in human hepatocellular carcinoma and its clinical implication

AIM:To investigate the methylation status of secreted protein acidic and rich in cysteine(SPARC) in human hepatocellular carcinoma(HCC) and evaluate its clinical implication.METHODS:The methylation status of SPARC was analyzed in one HCC cell line(SMMC-7721) and 60 pairs of HCC and corresponding nontumorous tissues by methylation-specific polymerase chain reaction and bisulfite sequencing.The expression of SPARC mRNA and protein were examined by reverse transcription polymerase chain reaction and immunohistochemistry,respectively.The correlations between the methylation status and the gene expression,the clinicopathological parameters,as well as the prognosis after surgery were analyzed.RESULTS:In the SMMC-7721 cell line,the loss of SPARC expression was correlated with the aberrant methylation and could be reactivated by the demethylating agent 5-aza-2'-deoxycytidine.Methylation frequency of SPARC in HCC was significantly higher than that in the corresponding nontumorous tissues(45/60 vs 7/60,P < 0.001),and it was correlated with the pathological classification(P = 0.019).The downregulation of the SPARC mRNA expression in HCC was correlated with the SPARC methylation(P = 0.040).The patients with methylated SPARC had a poorer overall survival than those without methylated SPARC(28.0 mo vs 41.0 mo,P = 0.043).CONCLUSION:Aberrant methylation is an important mechanism for SPARC inactivation in HCC and SPARC methylation may be a promising biomarker for the diagnosis and prognosis of HCC.

Levels of chemical element contents in thyroid as potential biomarkers for cancer diagnosis (a preliminary study)

Aim:Thyroid cancer is an internationally important health problem.The aim of this exploratory study was to evaluate whether significantchanges in the thyroid tissue levels of Al,B,Ba,Br,Ca,Cl,Cu,Fe,I,K,Li,Mg,Mn,Na,P,S,Si,Sr,V,and Zn exist in the malignantly transformed thyroid.Methods:Thyroid tissue levels of twenty chemical elements were prospectively evaluated in 41 patients with thyroid malignant tumors and 105 healthy inhabitants.Measurements were performed using a combination of non-destructive and destructive methods:instrumental neutron activation analysis and inductively coupled plasma atomic emission spectrometry,respectively.Tissue samples were divided into two portions.One was used for morphological study while the other was intended for trace element analysis.Results:It was found that contents of Al,B,Br,Ca,Cl,Cu,K,Mg,Mn,Na,P,S,and Si were significantly higher(approximately 3.2,4.6,9.3,1.8,2.3,3.6,1.6,1.6,1.6,1.2,2.5,1.1,and 2.8 times,respectively)while content of I lower(nearly 26 times)in cancerous tissues than in normal tissues.Conclusion:There are considerable changes in chemical element contents in the malignantly transformed tissue of thyroid.

Developing DNA methylation-based diagnostic biomarkers

An emerging paradigm shift for disease diagnosis is to rely on molecular characterization beyond traditional clinical and symptom-based examinations. Although genetic alterations and transcription signature were first introduced as potential biomarkers, clinical implementations of these markers are limited due to low reproducibility and accuracy. Instead, epigenetic changes are considered as an alternative approach to disease diagnosis. Complex epigenetic regulation is required for normal biological functions and it has been shown that distinctive epigenetic disruptions could contribute to disease pathogenesis. Disease-specific epigenetic changes, especially DNA methylation, have been observed,suggesting its potential as disease biomarkers for diagnosis. In addition to specificity, the feasibility of detecting disease-associated methylation marks in the biological specimens collcted noninvasively,such as blood samples, has driven the clinical studies to validate disease-specific DNA methylation changes as a diagnostic biomarker. Here, we highlight the advantages of DNA methylation signature for diagnosis in different diseases and discuss the statistical and technical challenges to be overcome before clinical implementation.

Blood Biomarkers in Minor Stroke and Transient Ischemic Attack

Minor stroke and transient ischemic attack（TIA）are common disorders with a high rate of subsequent disabling stroke, so the early recognition and management of minor stroke and TIA is of great importance. At the moment, the diagnosis of these disorders is based on neurologic deficits in a stroke-clinician＇s examination of the patient, supplemented by the results of acute brain imaging.However, high variability in TIA diagnosis has been reported between physicians, even trained vascular neurologists, and image-based diagnostic confirmation is not always readily available. Some patients still have ischemic events despite sustained standard secondary preventive therapy. Blood biomarkers are promising to aid in the diagnosis, risk stratification, and individual treatment of minor stroke and TIA. Some studies are being conducted in this field. This mini-review aims to highlight potential biomarkers for diagnosis and those helpful in predicting the risk of future stroke and the selection of treatment.

Tiny But Mighty:Promising Roles of MicroRNAs in the Diagnosis and Treatment of Parkinson's Disease

Parkinson＇s disease （PD） is the second most common age-related neurodegenerative disorder after Alzheimer＇s disease. To date, the clinical diagnosis of PD is primarily based on the late onset of motor impairments. Unfortunately, at this stage, most of the dopaminergic neurons may have already been lost, leading to the limited clinical benefits of current therapeutics. Therefore, early identification of PD, especially at the prodromal stage, is still a main challenge in the diagnosis and management of this disease. Recently, microRNAs （miRNAs） in cerebrospinal fluid or peripheral blood have been proposed as putative biomarkers to assist in PD diagnosis and therapy. In this review, we systematically summarize the changes of miRNA expression profiles in PD patients, and highlight their putative roles in the diagnosis and treatment of this devastating disease.

Diagnostic value of the neutrophil-to-lymphocyte ratio and the combination of serum CA-125 for stages Ⅲ and Ⅳ endometriosis

Background Currently, all the diagnostic indicators for endometriosis lack perfect sensitivity and specificity. According to the characteristic of endometriosis, we analyzed the new biomarker neutrophil-to-lymphocyte ratio （NLR） and the combination of NLR and serum CA-125 to investigate their diagnostic value for identifying stages III and IV endometdosis. Methods The values of serum CA-125 and routine blood tests were collected from 197 patients with endometriosis, 102 with benign tumors and 112 healthy individuals. We investigated the sensitivity and specificity of NLR and its combination with serum-CA-125 for diagnosing stages III and IV endometriosis by using receiver operating characteristic （ROC）. Results The mean values of NLR, the combination of serum CA-125 and NLR （combination） of the groups with stages III and IV endometriosis were significantly higher than the other two groups. Serum CA-125, NLR, and the combined biomarkers could significantly discriminate the stages Ill and IV endometriosis group from the other two groups （P〈0.05）. NLR shows a lower sensitivity of 57.9% and specificity of 65.2% with a cutoff value at 1.82. And the combination of biomarkers has the highest AUC of 0.949 with a sensitivity of 86.8% and specificity of 92.0% at the cutoff value of 44.40. In addition, for patients with negative CA-125, 55.36% and 53.57% of the patients were able to be diagnosed with endometriosis by using NLR alone and the combination of biomarkers. Conclusion For diagnosing stages III and IV endometriosis, the neutrophil-to-lymphocyte ratio is a better adjuvant to serum CA-125, and the neutrophil-to-lymphocyte ratio is valuable in diagnosing stages III and IV endometriosis for patients with negative serum CA-125.

Application of serum surface-enhanced laser desorption/ionization proteomic patterns in distinguishing lung cancer patients from healthy people

Screening and early diagnosis of lung cancer relies mainly on chest X-ray, low-dose computed tomography, bronchoscopy, sputum cytology, and measurement of tumor markers such as carcinoembryonic antigen (CEA), cytokeratin-19 fragments (Cyfra21-1), and neuron-specific enolase (NSE). However, all these methods lack adequate sensitivity and/or specificity. 1-3 Better methods are therefore urgently needed in screening and early diagnosis of lung cancer, and proteomic fingerprinting represents a promising approach. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), an innovative proteomic technology, has overcome many of the limitations of two-dimensional electrophoresis (2D) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). 4,5 Recently, this technology has been successfully used to distinguish pancreatic, ovarian and prostate cancer patients from healthy control subjects. 5-7 The aim of the current study was to investigate the application of serum SELDI protein profiling in distinguishing lung cancer patients from healthy persons.