Novel coronavirus (2019-nCoV) is the pathogen of COVID-19. Some severe cases may suffer from respiratory failure or even death, which poses a great challenge to global public health. 2019-nCoV proteins not only participate in virus proliferation, but also play an important role in antagonizing host innate immune response, especially interferon response. In this paper, 2019-nCoV proteins involved in regulating host interferon response and the complex interaction between 2019-nCoV and interferons were summarized, aiming to provide a theoretical reference for the prevention and control of COVID-19.

Objective:To investigate the clinicopathological features, diagnosis and prognosis of diffuse leptomeningeal glioneuronal tumor (DLGNT).Methods:Five cases of DLGNT diagnosed from January 2016 to January 2020 were collected from Xuanwu Hospital, Capital Medical University. The clinical features, histopathologic characteristics, immunohistochemical and molecular genetic findings and prognosis were analyzed and the relevant literature was reviewed.Results:The five patients (two males and three females) were aged 2 to 52 years (median 11 years), and had history of increased intracranial pressure (headache and vomiting) or limb weakness. Three of them were younger than 16 years of age. The imaging studies showed diffuse intracranial and intraspinal nodular leptomeningeal thickening and enhancement, with or without parenchymal involvement. At times there were associated small cyst-like lesions. Imaging interpretations were inflammatory lesions in three cases and space occupying lesions in two. Microscopically, in three cases the tumors showed low to moderate cellularity, consisting of relatively monomorphous oligodendrocyte-like cells arranged in small nests or diffusely distribution. No mitosis and necrosis were observed. In two cases there were increased cellularity with a diffuse honeycomb pattern. The tumor showed mild to moderate polymorphism with hyperchromatic nuclei. Mitosis, endothelial vascular proliferation and glomeruloid vessels were seen. Necrosis was absent. The tumor cells in all five cases were positive for synaptophysin,Olig2 and negative for IDH1 and H3 K27M. GFAP was focally positive in four cases and only one case expressed NeuN partly. The Ki-67 labeling index was 1%-35%. BRAF fusion was detected in four cases. Genetic analysis showed solitary 1p deletion in two cases (2/5), while all cases were negative for 1p/19q co-deletion (0/5). The five patients were followed up for 13 to 28 months (median 15 month). One patient died after 27 months. There was no evidence of tumor progression in the remaining four patients.Conclusions:DLGNT is rare and easily confused with other central nervous system tumors and inflammatory lesions. Therefore, the diagnosis of DLGNT should be made based on comprehensive information including imaging, morphologic and corresponding immunohistochemical examinations and molecular genetics to avoid misdiagnosis and delay in management.

Objective: To investigate the clinicpathologic features and probable mechanisms of massive subcortical heterotopia. Methods: Clinical data, histologic features and neuropathologic data were analyzed in five cases of massive subcortical heterotopia collected from Xuanwu Hospital, Capital Medical University from January 2014 to October 2017. Results: All five patients (three males and two females) had a history of refractory epilepsy with a mean period of 15.4 years (range 7 to 21 years). The median age at surgery was 28.6 years(range 20 to 39 years). Magnetic resonance imaging showed that the lesions were located in the temporal lobe (two cases), parietal lobe (one case), both temporal and occipital lobes (one case) and both temporal and parietal lobes (one case). Pathologic examination disclosed that massive gray matter in subcortical and deep white matter with various shape and size. Moreover, one case also showed subpial and periventricular heterotopias and polymicrogyria. Polymicrogyria or hippocampal sclerosis were seen in the remaining three cases. None of the five patients experienced seizure attacks during the follow-up period. Conclusions Heterotopia is malformations due to abnormal neuronal migration. Massive subcortical heterotopia due to widespread abnormal neuronal migration is relatively rare. The mechanism of heterotopia together with polymicrogyria needs further discussion.

Objective To investigate the characteristics and treatment for pneumatosis cystoides intestinalis (PCI). Methods Data of 12 PCI patients admitted to General Hospital of Tianjin Medical University from 1997 to 2015 were analyzed. The causes, endoscopic characteristics, therapeutic effects and prognosis were evaluated. Results Four cases were primary PCI due to long?term exposure to trichloroethylene or unknown reasons, while 8 other cases were secondary to Behcet's disease, connective tissue disease, emphysema, diabetes, therioma, etc. Endoscopic findings included bubble?like, linear,cobblestone?like, graped or beaded gas cysts, involving sigmoid in 6 cases, ascending colon in 3, descending colon in 2, duodenum in 2 and rectum in 1. After combination of medicinal and endoscopic treatment, symptoms of 8 patients were relieved, and the condition of 2 patients improved, while 2 patients died of malignancy. Conclusion Pneumatosis intestinalis is a rare disease, usually secondary to other diseases, which can be diagnosed by colonoscopy and ultrasonic endoscopy. Pathogenesis of PCI is still unclear. Single PCI can be cured with endoscopic resection. Multiple PCI can be managed with cyst clipping, antibiotics and intestinal flora regulator. Treatment of the original disease and early detection of complications can improve the prognosis and reduce recurrence of PCI.

Objective: To investigate the usefulness of loss of CIC expression as the prescreening detection of 1p/19q co-deletion in the diagnosis of oligodendroglial tumors and its prognostic implication. Methods: The retrospective study included 113 oligodendroglial tumors diagnosed in the Department of Pathology, Xuanwu Hospital, Capital Medical University. Expression of CIC protein was detected by immunohistochemistry, and the 1p/19q co-deletion by fluorescence in situ hybridization in all the tumors; and the correlation of the loss of protein and 1p/19q co-deletion with prognosis was assessed. Results: The rate of negative CIC protein expression was 59.3% (67/113) in 113 oligodendroglial tumors. CIC protein expression was differentially lost in various gliomas, 85.7% (42/49) in pure oligodendrogliomas and 39.1% (25/64) in mixed oligodendroglial tumors (P<0.01). The loss of CIC protein expression showed a sensitivity of 76.1% (54/71), specificity 71.1% (27/38), false positive rate of 16.9% (11/65), and a false negative rate of 38.6% (17/44). In 63 cases integrated diagnosis as oligodendroglial tumors with mutant IDH and 1p/19q co-deletion, the loss of CIC protein expression was 81.0% (51/63); the sensitivity and specificity were increased to 81.0% (51/63) and 76.9% (20/26), and the false positive rate and false negative rate decreased to 10.5% (6/57) and 37.5% (12/32), respectively. By using Kaplan-Meier analysis, the CIC negative group showed a trend towards better outcome than the CIC positive group, but there was no statistical difference (overall survival: P=0.218; progression free survival: P=0.249). Conclusions Detection of the lost CIC protein expression can predict the chromosome 1p/19q co-deletion. In oligodendroglial tumors with IDH mutant and 1p/19q co-deletion, there is no relation between prognosis and CIC protein expression.

Objective: To investigate the diagnostic and prognostic implications of ATRX mutation and p53 mutation in patients with glioma. Methods: The clinicopathologic and molecular features of Chinese adult glioma patients, including diffuse and anaplastic astroastrocytoma with IDH mutation, oligodendroglioma and anaplastic oligodendroglioma with IDH mutation and 1p/19q co-deletion and diffuse astroastrocytoma with IDH wild type were reviewed and tested for ATRX loss expression and p53 overexpression. Results: Loss of ATRX expression was seen in 85.19% (23/27) diffuse and anaplastic astroastrocytoma with IDH mutation, higher than that of oligodendroglial tumors (0/53; P<0.01). Loss of ATRX expression was strongly linked to p53 overexpression(69.57%, 16/23). The patients who lost ATRX expression combined with normal p53 expression survived longer(P=0.013). Conclusions ATRX mutation is a molecular marker for astrocytic tumors. ATRX mutation combined with p53 mutation can predict prognosis of patients with glioma.

Objective To evaluate the effects of OPRM1All8G and CYP3A4*18B genetic polymorphism and the interaction on postoperative analgesia with fentanyl in the patients undergoing radical resection of lung cancer.Methods One hundred and thirty-nine patients (native of Henan province),aged 40-64 yr,weighing 40-70 kg,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective radical resection of lung cancer under general anesthesia,were enrolled in this study.The polymorphic sites of the OPRM1All8G and CYP3A4*18B allele were analyzed by using polymerase chain reaction technique and ABI 3130 Genetic Analyzer.The patients were divided into wild homozygote group (group AA,group *1/*1),heterozygote group (group AG,group * 1/*18B) and mutation homozygote group (group GG,group *18B/*1SB) according to their genotypes.The patients were divided into 7 groups according to the interaction between the two genes:AA plus *1/*1 group (group Ⅰ),AA plus *1/*18B group (group Ⅱ),AG plus *1/*1 group (group Ⅲ),AG plus *1/*18B group (group Ⅳ),GG plus * 1/*1 group (group Ⅴ),GG plus *1/*18B group (group Ⅵ) and *18B/*18B group (group Ⅶ).Patientcontrolled intravenous analgesia with fentanyl was started at the end of surgery to maintain the visual analogue scale ≤ 3 points.The amount of fentanyl used within 24 and 48 h after surgery was recorded,and the occurrence of adverse reactions within 48 h after surgery was observed.Results The amount of fentanyl used within 24 and 48 h after surgery was significantly higher in group GG than in group AA (P＜0.05).The amount of fentanyl used within 48 h after surgery was significantly lower in group *18B/*18B than in group *1/*1 (P＜0.05).The amount of fentanyl used within 48 h after surgery was significantly higher in Ⅱ and Ⅳ groups than in group Ⅰ,in group Ⅲ than in group Ⅱ,in group Ⅴ than in Ⅰ-Ⅳ groups,and in group Ⅵ than in Ⅱ and Ⅳ groups,and was significantly lower in group Ⅶ than in Ⅰ-Ⅵ groups (P＜ 0.05).There was no significant difference in the incidence of adverse reactions within 48 h after surgery between groups (P＞0.05).Conclusion OPRM1A1l8G and CYP3A4*18B genetic polymorphism and the interaction are the genetic factors contributing to individual variation in fentanyl pharmacodynamics in the patients undergoing radical resection of lung cancer.

Objective To explore the clinicopathological features and imaging characteristics of non-Langerhans cell histiocytosis in central nerve system,thus to facilitate the diagnosis and differential diagnosis.Methods A total of ten cases were enrolled in the study,with seven cases of Rosai-Dorfman disease(RDD) and three cases of xanthoma disseminatum (XD).Data on the clinicopathological features,imaging,immunophenotype and prognosis were collected and analyzed.Results Seven patients with RDD,5 males and 2 females with the mean age of 46.7 years old,all presented as dural-based or intraparenchymal hypo-to isointense lesions on T1 and T2 with post-contrast enhancement.The polymorphous admixture of histiocytes,lymphocytes and plasma cells was observed in a fibrous stroma,with emperipolesis of some histiocytes.The immunohistostaining of CD11c,CD68,MAC387 and S-100 was positive in the histiocytes,while the staining of CD1α was negative.Five patients recovered after the operation,while one patient died of the disease.All the 3 XD patients were female,with the median age of 20.7 years old.All XD patients presented as multiple intraparenchymal hypointense lesions on T1 and hyperintense lesions on T2 with post-contrast enhancement.The infiltration of foam-like histiocytes,a few Touton giant cells,lymphocytes and eosnophils was observed in all XD patients.The immunohistostaining of CD68 and CD11c was positive in the histiocytes and that of MAC387 partly positive,while the staining of S-100 and CD1α was negative.One XD patient survived well,while another one died of the disease.Conclusions The diagnosis of RDD and XD should be based on their typical morphology and immunophenotype and should be differentiated from Langerhans cell histiocytosis and other non-Langerhans cell histiocytosis.Non-Langerhans cell histiocytosis in central nerve system often presents untypical clinical presentation and imaging features,thus the communication and cooperation between clinician and pathologist is needed.

OBJECTIVETo study the expression of autophagy-related proteins (Beclin-1, LC3 and p62) in brain tissue with malformations of cortical development and related molecular pathogenesis.

METHODSThe brain tissue of 18 cases with epileptogenic foci resection, including 6 cases of tuberous sclerosis complex (TSC), 6 cases of focal cortical dysplasia type IIb (FCD IIb) and 6 cases of focal cortical dysplasia type I (FCD I), were retrieved. Immunohistochemical study for Beclin-1, LC3 and p62 proteins was performed. The degree of positivity for Beclin-1 and LC3 proteins was compared. Western blot was used to quantitatively analyze the LC3 protein in focal lesion of each disease groups.

RESULTSImmunohistochemical study showed that the three proteins were mainly expressed in the dysmorphic neurons and balloon cells/giant cells of TSC and FCD IIb. The positivity was more intense in the dysmorphic neurons than the other cell types. Immunostaining for Beclin-1 showed granular or diffuse cytoplasmic positivity, in addition to the strong expression in axons. On the other hand, LC3 showed diffuse or perinuclear cytoplasmic expression. The staining for p62 was mainly cytoplasmic or perinuclear and sometimes nuclear. In FCD type I, only individual cells showed positive expression for the three proteins. The number of Beclin-1 and LC3-positive cells was larger in TSC group, followed by FCD IIb group and FCD I group.And there were significant differences between TSC group and FCD I group, as well as FCD IIb group and FCD I group (P<0.05). Quantitative expression of LC3 protein by Western blot showed smaller amount in TSC group, followed by FCD IIb group and FCD I group.

CONCLUSIONSThe dysmorphic neurons and balloon cells/giant cells of TSC and FCD IIb show abnormality in autophagy, resulting in intracytoplasmic protein accumulation. There are differences in molecular pathogenesis in these cell types.

OBJECTIVE To explore the genetic mechanism for a family affected with cardiac conduction block. METHODS Affected family members were screened for potential mutations of known candidate genes. As no pathogenic mutation was found, two patients and one healthy member from the family were further analyzed by exomic sequencing followed by Sanger sequencing. The pathogenicity of suspected mutation was analyzed using bioinformatics software. RESULTS Sequencing of the full exome has identified a c.G1725T mutation in the CLCA2 gene. Sanger sequencing has detected the same mutation in all five patients, but not in the normal member from the family. Bioinformatics analysis indicated that the mutation has resulted in substitution of the 575th amino acid cysteine (C) by tryptophan (W). The site is highly conserved and becomes pathogenic with the mutation. CONCLUSION The heterozygous c.G1725T mutation in exon 11 of the CLCA2 gene probably underlies the disease and fit the autosomal dominant pattern of inheritance.
Amino Acid Sequence ; Chloride Channels ; genetics ; Computational Biology ; Female ; Heart Block ; genetics ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation