Objective To explore the immunopathologic mechanism underlying the inflammatory response after severe acute respiratory syndrome（SARS） invasion.Methods Pathway focused cDNA microarrays were employed for comparision of the gene expression patterns in 16HBEs treated with interferon-γ(IFN-γ) or the S protein of SARS-CoV.The S proteins were administered to BALB/c mice and the pathological changes of lung and spleen were observed.Results S protein activated JAK/STAT signal pathway in the 16HBEs with inducible protein 10（IP-10） gene expression，and the specific inhibitors of the JAK/STAT signal pathway were able to downregulate the induction of IP-10.The mice instilled intracheally with S proteins revealed obvious acute diffuse damage and increased IP-10 expression and CD68+ macrophages infiltration in both lung and spleen tissues.In contrast，the treatment with JAK3 inhibitors attenuated lung and spleen injury in the mice.Conclusion Our findings support that the activation of JAK/STAT pathway induced by SARS-CoV S protein plays a key role in promotion of an IFN -γ inducible chemokine cascade，which can help in the development of novel drug and therapeutics for prevention and treatment of SARS.
Since the first case of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019, the virus has spread rapidly around the world and has become a global public health problem. In the process of this virus epidemic, compared with the general population, cancer patients are considered to be highly susceptible people, especially the lung cancer patients. Some studies have shown that angiotensin converting enzyme 2 (ACE2) may be the pathway for SARS-CoV-2 to infect the host. At the same time, ACE2 is often abnormally expressed in non-small cell lung cancer. Therefore, understanding the respective mechanisms of ACE2 in COVID-19 and non-small cell lung cancer has extremely important reference value for the study of vaccines and therapeutic drugs, and also provides meaningful guidance for the protection of patients with lung cancer during the epidemic. This article reviews the possible invasive mechanism of ACE2 in SARS-CoV-2 and its abnormal expression in non-small cell lung cancer.
Objective The ReHo, ALFF, fALFF of resting-state functional magnetic resonance imaging (RS-fMRI) technology were used to study the influencing factors and neural mechanism of cognitive dysfunction in patients with benign epilepsy of childhood with centrotemporal spikes (BECT). Methods Fourteen patients were enrolled (from April 2015 to March 2018) from epilepsy specialist outpatients and Functional Department of Neurosurgery of Tianjin Medical University General Hospital. They underwent the long term VEEG monitoring (one sleep cycle was included at least), the Wechsler Intelligence Scale (China Revised), the head MRI and RS-fMRI examinations. Spike-wave index (SWI), FIQ, VIQ, PIQ scores were calculated. According to full-scale IQ (FIQ), they were divided into two groups: FIQ<90 (scores range from 70 to 89, the average score was 78.3±8.9, 6 cases) and FIQ≥90 (scores range from 90 to 126, the average score was 116.6±12.9, 8 cases). SPSS21.0 statistical software was used to compare the general clinical data and SWI of the two groups, and the correlation between clinical factors and the evaluation results of Wechsler Intelligence Scale was analyzed. The RS-fMRI images were preprocessed and the further data were analysed by two independent samplest-test under the whole brain of regional homogeneity (ReHo), amplitude of low frequency fluctuation (ALFF) and fractional of ALFF (fALFF) methods. The differences of brain activation regions in RS-fMRI between the two groups were observed, and the results of general clinical data, SWI and cognitive function test were compared and analyzed comprehensively. Results The differences of SWI were statistically significant (P<0.05): FIQ<90 group were greater than FIQ≥90 group. The FIQ, VIQ and PIQ of two groups were negatively correlated with SWI (P<0.05). And the FIQ and PIQ were negatively correlated with the total number of seizures (P<0.05). Compared with FIQ≥90 group by two samplet-test based on whole level ReHo, ALFF, fALFF methods, deactivation of brain regions of FIQ<90 group include bilateral precuneus, posterior cingulate and occipital lobe, and enhanced activation of brain regions include left prefrontal cortex, bilateral superior frontal gyrus medial and right precentral gyrus, supplementary motor area, angular gyrus, supramarginal gyrus, middle temporal gyrus, bilateral insular lobe and subcortical gray matter structures. Conclusions Frequent epileptic discharges during slow wave sleep and recurrent clinical episodes were risk factors for cognitive impairment in BECT patients. Repeated clinical seizures and frequent subclinical discharges could cause dysfunction of local brain areas associated with cognition and the default network, resulting in patients with impaired cognitive function.
The raging global epidemic of coronavirus disease 2019 (COVID-19) not only poses a major threat to public health, but also has a huge impact on the global health care system and social and economic development. Therefore, accelerating the development of vaccines and antibody drugs to provide people with effective protection and treatment measures has become the top priority of researchers and medical institutions in the field. At present, several vaccines and antibody drugs targeting SARS-Cov-2 have been in the stage of clinical research or approved for marketing around the world. In this manuscript, we summarized the vaccines and antibody drugs which apply genetic engineering technologies to target spike protein, including subunit vaccines, viral vector vaccines, DNA vaccines, mRNA vaccines, and several neutralizing antibody drugs, and discussed the trends of vaccines and antibody drugs in the future.
Objective To explore the clinical value of Persyst automatic detection of spike waves in adult patients with temporal lobe epilepsy. Methods EEG recordings were continuously concluded from the Epilepsy Unit of the First Affiliated Hospital of Soochow University during 2019.1.1 to 2019.12.31. Two EEG experts certified by the Chinese Anti-Epileptic Association marked interictal epileptic discharge in the long-time electroencephalogram that meet the criteria. Consistent results of the two experts were seen as the "golden standard". The sensitivity and false positive rates were calculated compared with the automatic test results of Persyst version 11, 13 and 14. Results 7 cases were included, each with a recording time of 24~25 hours and a total of 169 hours. Two expert readers achieved the consistency of 43.09%. Spike waves detected automatically were much more than manually. The sensitivity was as high as 62.26%, 77.0% and 67.28%. The lowest false positive rate was 0.37/min, 0.85/min and 0.46/min respectively. Automatic analysis achieved an average workload reduction of 14.59%~37.05%. Conclusions Persyst automatic spike detection has the acceptable sensitivity and false positive rate. It differs from versions and need to be further combined with expert readers.Less workload and accuracy can be balanced by setting reasonable perception parameter.
Objective To observe the inhibition of SARS-CoV-2 spike protein (S-protein) on the proliferation of human retinal pigment epithelium (RPE) cells. MethodsSARS-CoV-2 S-protein gene fragment expression plasmid (p3xflag-S) was constructed and transfected into human RPE, HEK293 cells. DNA sequencing was used for identification, and the expression of Flag-S was detected by Western blot. HEK293 cells were divided into the cells 1, 2, 3 and 4 and transfected with GFP11 plasmid and vector, GFP1-10plasmid and vector, transfected with GFP11 and pCMV-HA-ACE2 plasmid, GFP1-10 and p3xflag-S plasmid. Cell 1 was co-cultured with cell 2 (control group 1), cell 2 with cell 3 (control group 2), cell 3 with cell 4 (observation group), and cell 1 mixed with cells 2, 3 and 4 (control group 3). Bright-field microscopy and fluorescence microscopy were used to observe cell fusion. RPE cells were divided into control group and overexpression S-protein group. The cell cycle was detected by flow cytometry; the cell proliferation level was detected by Counting Kit 8 (CCK-8); and the S-protein expression level in RPE cells was detected by Western blot. The Student’s t-test was performed for comparison between groups. ResultsDNA sequence assay showed that S-protein cDNA was fused with flag-tagged protein. Western blot assay showed thatS-protein-related expression was elevated in transfected HEK293 cells compared with untransfected p3xflag-S cells. Large, multinucleated fused cell clusters were visible under bright-field microscopy; multiple nuclear with distinct green fluorescence were visible in the fused cells under fluorescence microscopy. Western blot assay showed elevated S-protein-related expression in transfected p3xflag-S plasmid RPE cells compared to untransfected p3xflag-S plasmid RPE cells. CCK-8 results showed that the proliferative capacity of RPE cells in the S-protein overexpression group was significantly reduced compared with the control group, with statistically significant differences (t=22.70, 16.75, 23.38; P<0.000 1). The results of flow cytometry showed that the G1 phase cells in the control and overexpression S-protein groups were 41.1% and 67.0%, respectively; compared with the control group, the G1 phase cells in the overexpression S-protein group were significantly higher, and the difference was statistically significant (t=4.76, P=0.018). The apoptosis rate was significantly increased in the S-protein overexpression group compared with the control group, and the difference was statistically significant (t=4.91, P=0.008). ConclusionOverexpression of the SARS-CoV-2 spike protein reduced the proliferation of human RPE cells.
Prolonged disorders of consciousness (pDOC) are pathological conditions of alterations in consciousness caused by various severe brain injuries, profoundly affecting patients’ life ability and leading to a huge burden for both the family and society. Exploring the mechanisms underlying pDOC and accurately assessing the level of consciousness in the patients with pDOC provide the basis of developing therapeutic strategies. Research of non-invasive functional neuroimaging technologies, such as functional magnetic resonance (fMRI) and scalp electroencephalography (EEG), have demonstrated that the generation, maintenance and disorders of consciousness involve functions of multiple cortical and subcortical brain regions, and their networks. Invasive intracranial neuroelectrophysiological technique can directly record the electrical activity of subcortical or cortical neurons with high signal-to-noise ratio and spatial resolution, which has unique advantages and important significance for further revealing the brain function and disease mechanism of pDOC. Here we reviewed the current progress of pDOC research based on two intracranial electrophysiological signals, spikes reflecting single-unit activity and field potential reflecting multi-unit activities, and then discussed the current challenges and gave an outlook on future development, hoping to promote the study of pathophysiological mechanisms related to pDOC and provide guides for the future clinical diagnosis and therapy of pDOC.