COVID-ONE-humoral immune: The One-stop Database for COVID-19-specific Antibody Responses and Clinical Parameters

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (COVID-ONE humoral immune). COVID-ONE humoral immunity is based on a dataset that contains the IgG/IgM responses to 21 of 28 known SARS-CoV-2 proteins and 197 spike protein peptides against 2,360 COVID-19 samples collected from 783 patients. In addition, 96 clinical parameters for the 2,360 samples and information for the 783 patients are integrated into the database. Furthermore, COVID-ONE humoral immune provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the "START" button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-humoral immune is freely available at www.COVID-ONE.cn.

COVID-ONE-humoral immune: The One-stop Database for COVID-19-specific Antibody Responses and Clinical Parameters

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (COVID-ONE humoral immune). COVID-ONE humoral immunity is based on a dataset that contains the IgG/IgM responses to 21 of 28 known SARS-CoV-2 proteins and 197 spike protein peptides against 2,360 COVID-19 samples collected from 783 patients. In addition, 96 clinical parameters for the 2,360 samples and information for the 783 patients are integrated into the database. Furthermore, COVID-ONE humoral immune provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the "START" button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-humoral immune is freely available at www.COVID-ONE.cn.

Systematic profiling of SARS-CoV-2 specific IgG epitopes at single amino acid resolution

SARS-CoV-2 specific IgG responses play critical roles for patients to recover from COVID-19, in-depth dissecting of the IgG responses on systems level is of great interest. Herein, we adopted a newly developed high-throughput epitope mapping technology (AbMap), analyzed 55 COVID-19 convalescent sera and 226 antibody samples enriched by specific proteins or peptides from these sera. We revealed three areas that are rich of IgG epitopes, two are on Spike protein but outside of RBD, and one is on Nucleocapsid protein. We identified 29 significant epitopes on Spike protein, from two of these significant epitopes, two critical epitope residues were found, i. e., D936 and P1263, which are highly related to the infectivity of SARS-CoV-2 In summary, we provided the first global map of IgG binding epitopes for SARS-CoV-2 at single amino acid resolution. This map will facilitate the precise development of therapeutic antibodies and vaccines. HIGHLIGHTSO_LIA map of SARS-CoV-2 specific IgG binding epitopes at single amino acid resolution C_LIO_LITwo areas outside of RBD that are rich of significant epitopes were identified C_LIO_LIOne area rich of significant epitopes was determined on Nucleocapsid protein C_LIO_LITwo critical epitope residues (D936 and P1263) on Spike protein are highly related to the infectivity of SARS-CoV-2 C_LI

Linear epitopes of SARS-CoV-2 spike protein elicit neutralizing antibodies in COVID-19 patients

SARS-CoV-2 outbreak is a world-wide pandemic. The Spike protein plays central role in cell entry of the virus, and triggers significant immuno-response. Our understanding of the immune-response against S protein is still very limited. Herein, we constructed a peptide microarray and analyzed 55 convalescent sera, three areas with rich linear epitopes were identified. Potent neutralizing antibodies enriched from sera by 3 peptides, which do not belong to RBD were revealed.

Global profiling of SARS-CoV-2 specific IgG/ IgM responses of convalescents using a proteome microarray

COVID-19 is caused by SARS-CoV-2, and has become a global pandemic. There is no highly effective medicine or vaccine, most of the patients were recovered by their own immune response, especially the virus specific IgG and IgM responses. However, the IgG/ IgM responses is barely known. To enable the global understanding of SARS-CoV-2 specific IgG/ IgM responses, a SARS-CoV-2 proteome microarray with 18 out of the 28 predicted proteins was constructed. The microarray was applied to profile the IgG/ IgM responses with 29 convalescent sera. The results suggest that at the convalescent phase 100% of patients had IgG/ IgM responses to SARS-CoV-2, especially to protein N, S1 but not S2. S1 purified from mammalian cell demonstrated the highest performance to differentiate COVID-19 patients from controls. Besides protein N and S1, significant antibody responses to ORF9b and NSP5 were also identified. In-depth analysis showed that the level of S1 IgG positively correlate to age and the level of LDH (lactate dehydrogenase), especially for women, while the level of S1 IgG negatively correlate to Ly% (Lymphocyte percentage). This study presents the first whole picture of the SARS-CoV-2 specific IgG/ IgM responses, and provides insights to develop precise immuno-diagnostics, effective treatment and vaccine. HighlightsO_LIA SARS-CoV-2 proteome microarray contains 18 of the 28 predicted proteins C_LIO_LIThe 1st global picture of the SARS-CoV-2 specific IgG/ IgM response reveals that at the convalescent phase, 100% of patients have IgG/ IgM responses to protein N and S1 C_LIO_LISignificant antibody responses against ORF9b and NSP5 were identified C_LIO_LIProtein S1 specific IgG positively correlates to age and LDH, while negatively to Ly% C_LI

Stroke-like Migraine Attacks after Radiation Therapy Syndrome / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To summarize the clinical presentation, pathogenesis, neuroimaging, treatment, and outcome of stroke-like migraine attacks after radiation therapy (SMART) syndrome, and to propose diagnostic criteria for this disorder.</p><p><b>DATA SOURCES</b>We searched the PubMed database for articles in English published from 1995 to 2015 using the terms of "stroke-like AND migraine AND radiation." Reference lists of the identified articles and reviews were used to retrieve additional articles.</p><p><b>STUDY SELECTION</b>Data and articles related to late-onset effects of cerebral radiation were selected and reviewed.</p><p><b>RESULTS</b>SMART is a rare condition that involves complex migraines with focal neurologic deficits following cranial irradiation for central nervous system malignancies. The recovery, which ranges from hours to days to weeks, can be partial or complete. We propose the following diagnostic criteria for SMART: (1) Remote history of therapeutic external beam cranial irradiation for malignancy; (2) prolonged, reversible clinical manifestations mostly years after irradiation, which may include migraine, seizures, hemiparesis, hemisensory deficits, visuospatial defect, aphasia, confusion and so on; (3) reversible, transient, unilateral cortical gadolinium enhancement correlative abnormal T2 and fluid-attenuated inversion recovery signal of the affected cerebral region; (4) eventual complete or partial recovery, the length of duration of recovery ranging from hours to days to weeks; (5) no evidence of residual or recurrent tumor; (6) not attributable to another disease. To date, no specific treatment has been identified for this syndrome.</p><p><b>CONCLUSIONS</b>SMART is an extremely rare delayed complication of brain irradiation. However, improvements in cancer survival rates have resulted in a rise in its frequency. Hence, awareness and recognition of the syndrome is important to make a rapid diagnosis and avoid aggressive interventions such as brain biopsy and cerebral angiography.</p>

Influence of edaravone on growth arrest and DNA damage-inducible protein 34 expression following focal cerebral ischemia-reperfusion in rats

Objective: To investigate the influence of edaravone on the expression of growth arrest and DNA damage-inducible protein 34 (GADD34). Methods: A total of 108 healthy male Sprague-Dawley rats were randomly divided into sham operation group, model group and edaravone group (36 cases for each group). Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h followed by reperfusion in Sprague-Dawley rats. Then, GADD34 expression was measured with immunohistochemistry at different time-points after reperfusion in the peri-infarct regions of all rats. Results: The GADD34 expression was detected in the peri-infarct regions of rats 1 h after reperfusion, which reached its peak 24 h after reperfusion. And edaravone could significantly down-regulate the GADD34 expression. Conclusions: Edaravon could down-regulate GADD34 expression, which suggests that edaravone may exert an important function in inhibiting endoplasmic reticulum stress reaction by scavenging free radicals in the upper stream.

Effects of chaihu shugan powder on the behavior and expressions of BDNF and TrkB in the hippocampus, amygdala, and the frontal lobe in rat model of depression / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effects of Chaihu Shugan Powder (CHSGP) on the behavior and the expressions of brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase receptors B (TrkB) in the hippocampus, amygdala, and the frontal lobe of depression model rats.</p><p><b>METHODS</b>Sixty adult Sprague-Dawley rats were randomly divided into 6 groups, i. e., the normal control group (NC), the model control group (MC), the CHSGP group, the disassembly 1 group (CI), the disassembly 2 group (CII), and the Fluoxetine control group (FC), 10 in each group. Except those in the NC, the rest rats were singly housed and exposed on an unpredicted sequence of mild stressor. From the fifteenth day, all rats were administered with equal volume of normal saline (to the NC group and the MC group) and of corresponding medicinal liquid (5.9 g/kg to the CHSGP group, 3.3 g/kg to the CI group, 2.6 g/kg to the CII group, and 1.8 mg/kg to the FC group) by gastrogavage for 2 successive weeks. The rats' body weight, sucrose consumption volume in the sucrose preference test, and times of grooming in the open field test were detected on the 0, 7th, 14th, 21st, 28th day, respectively. The mRNA expressions of BDNF and TrkB in the hippocampus, amygdala, and the frontal lobe were detected by immunohistochemical assay and Real-time fluorescent quantitation PCR.</p><p><b>RESULTS</b>Compared with the NC group, the rats' body weight was put up slowly in the MC group. The scores in the open field test decreased. The times of grooming and sucrose consumption volume were both reduced. The time of staying in central square was postponed. The mRNA expressions of BDNF and TrkB in the hippocampus, amygdala, and the frontal lobe decreased with statistical significance (P<0.05, P<0.01). Compared with the MC group, the behavior indices of rats in the CHSGP, CI, CII, and FC groups were significantly improved. The mRNA expressions of BDNF and TrkB in the hippocampus, amygdala, and the frontal lobe were obviously enhanced with statistical significance (P<0.05, P<0.01).</p><p><b>CONCLUSIONS</b>CHSGP could obviously improve the depressive state of the model rats. Its mechanism might be correlated with increasing the mRNA expressions of BDNF and TrkB in the hippocampus, amygdala, and the frontal lobe.</p>

Establishment and application of an analytical method for PINK1 gene exon copy number / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To establish a method for analyzing the PTEN-induced kinase 1 gene (PINK1) exon copy number and apply it to the analysis of PINK1 gene exon copy number variation (CNV) in patients with autosomal recessive early-onset Parkinsonism (AREP).</p><p><b>METHODS</b>Real-time PCR was used to analyze the exon copy number in 22 probands with AREP from unrelated Chinese Han families and 30 healthy controls.</p><p><b>RESULTS</b>Copy numbers of exons 1-8 of the PINK1 gene were analyzed, and satisfactory reaction conditions and primers for exons of the PINK1 gene were obtained. No exon CNV in the PINK1 gene was detected in this group.</p><p><b>CONCLUSION</b>An analytical method for PINK1 gene exon copy number was established. The exon CNV in the PINK1 gene was rare in Chinese patients with AREP.</p>