Objective To detect γ-secretase gene mutations in a large Chinese pedigree with acne inversa (AI).Methods Clinical evaluation was carried out in a large pedigree with AI through field investigation.Peripheral blood samples were obtained from 17 family members (11 affected and 6 unaffected) and 100 unrelated healthy human controls.DNA was extracted from the blood samples,and PCR was performed to amplify all the coding regions of PSEN 1,PSENEN and NCSTN genes followed by DNA sequencing analysis.Results There were 67 members over 5 generations in this family,of whom,25 (13 males and 12 females) were affected by AI.AI was inherited in an autosomal dominant manner in this family.Skin lesions were mainly distributed on the neck,back,chest and buttocks,and occasionally in subaxillary regions.DNA sequencing revealed a novel missense mutation,c.1258C＞ T (p.Q420XP),in the exon 11 of the NCSTN gene in 11 affected family members,which leads to a substitution of glutamine by a premature termination codon at amino acid 420 (p.Q420X).The mutation was undetected in either the unaffected members or the unrelated healthy controls,and had not been registered in the single nucleotide polymorphism (SNP) database in National Center for Biotechnology Information.Conclusions There is a novel heterozygous missense mutation,c.1258C ＞ T in the exon 11 of the NCSTN gene,which may be the molecular basis of pathogenesis of AI in this family.

Objective:To explore the expression of caveolin-1 (Cav-1) and Chitinase-40 (YKL-40) in acute cerebral infarction and the value of combined detection in prognosis evaluation.Methods:118 patients with acute cerebral infarction admitted to the First Affiliated Hospital of Hebei Northern University from January 2016 to June 2019 were selected as the research objects. According to the cerebral infarction volume, the patients were divided into small infarction group (<5 cm 3), middle infarction group (5-10 cm 3) and large infarction group (>10 cm 3). 108 healthy people were selected as the healthy control group. The serum levels of Cav-1 and YKL-40 were compared in the 3 groups, and the correlation between the degree of cerebral infarction and serum levels of Cav-1 and YKL-40 was analyzed. Receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of the expression levels of Cav-1 and YKL-40 in patients with acute cerebral infarction; the patients were followed up for one year and the prognosis was evaluated by modified Rankin Scale (mRS); the correlation between serum Cav-1 and YKL-40 and prognosis was analyzed. Results:The expression levels of serum Cav-1 and YKL-40 in patients with acute cerebral infarction were significantly higher than those in healthy group ( P<0.001). The serum levels of Cav-1 and YKL-40 were positively correlated with the infarct volume of acute cerebral infarction ( r=0.854, P=0.004; r=0.867, P=0.002). ROC curve analysis showed that the sensitivity, Youden index and area under ROC curve of Cav-1 (21.78 μg/L) combined with YKL-40 (158.69 ng/ml) in the diagnosis of acute cerebral infarction were 85.59%, 0.532 and 0.896 (95% CI: 0.741-0.932), respectively, which were significantly higher than those of single index ( P<0.05). At 8 and 12 months of follow-up, the proportion of death and mRS score in the positive group were significantly higher than those in the negative group ( P<0.05). Conclusions:The serum Cav-1 and YKL-40 levels are significantly higher in patients with acute cerebral infarction. The combined examination of Cav-1 and YKL-40 can improve the diagnostic efficiency and has potential application value for early diagnosis and prognosis prediction of patients.

Objective To investigate the effect of statin pretreatment on collateral circulation and prognoses of patients with cardiac large artery occlusive stroke.MethodsFifty-three patients with cardiac large artery occlusive stroke admitted to our hospital from January 2016 to July 2019 were selected. All patients had unilateral middle cerebral artery occlusion. DSA was used to evaluate the collateral flows, and the differences of collateral flows and prognoses in patients took statins before onset were compared with those did not take statins.ResultsAs compared with patients did not take statins, patients took statins had higher incidences of diabetes and coronary heart disease, lower content of low density cholesterol, higher proportion of patients with good collateral circulation (grading 3 to 4), and lower modified Rankin scale scores 3 months after surgery, with statistically significant differences (P< 0.05). Multivariate Logistic regression analysis showed that percentage of patients took statins was independent factors affecting collateral flow in patients with cardiac arterial occlusive stroke(OR=5.000, 95％CI: 1.136-22.006,P=0.033).ConclusionIn patients with cardiac large artery occlusive stroke, statin pretreatment could improve collateral flow and clinical prognoses.

Adult ; Age Factors ; Alcoholism ; complications ; China ; epidemiology ; Fatty Liver ; epidemiology ; etiology ; Female ; Humans ; Liver Diseases, Alcoholic ; epidemiology ; etiology ; Male ; Middle Aged ; Prevalence ; Sex Factors

Objective To evaluate the application value of serum tumor markers in small cell lung Cancer, and analyse the relationship between serum tumor markers and immunohistochemistry indicators.Methods The electrochemical luminescence technology was used to detect the concentration of carcino-embryonic anti-gen(CEA),neuronspecific enolase(NSE),cyto-keratin fragment 19(CYFRA21-1),the immunological lumines-cence technology was used to detect the concentration of ProGRP,the expression of Ki-67,TTF-1 were detec-ted by MaxVision immunohistochemistry methods,the date was analyzed by two independent sample rank sum test,rank correlation methods,chi-square test and ROC curve.Results The concentration of CEA,NSE,pro-gastrin-releasing peptide(ProGRP),CYFRA21-1 in SCLC were higher than that in benign disease,the concen-tration of CEA,NSE,ProGRP,CYFRA21-1 in extensive stage were higher than that in limited stage(P<0. 05),the difference was statistically significant.The ROC area of NSE,ProGRP were large,they were 0.972 and 0.965,the Kappa value of the NSE+ProGRP was 0.860,optimstic data consistency with "the gold stand-ard".There was a negative relationship between Ki-67 and CEA,NSE,ProGRP,the positive rate of TTF-1 was higher than CYFRA21-1,while lower than ProGRP,But NSE,CEA and TTF-1 have same results(P>0.05). Conclusion Combined detection NSE and ProGRP is of great value in the diagnosis and periods of SCLC,the sensibility and specificity of NSE+ProGRP was high in SCLC,he high expression of Ki-67 was not responsed the concentration of serum tumor markers,TTF-1 had the same results with NSE,while inferior to ProGRP in detect of SCLC.

Objective:To determine mutations in the PTPN11 gene in a family with LEOPARD syndrome.Methods:Clinical evaluation was carried out in a large pedigree with confirmed LEOPARD syndrome diagnosed in Hwa Mei Hospital, University of Chinese Academy of Sciences. Peripheral blood samples were obtained from 4 patients and 2 unaffected healthy members in the family, as well as 100 unrelated healthy controls. DNA was extracted from the blood samples, and PCR was performed to amplify all exons of the PTPN11 genes, followed by Sanger sequencing.Results:There were 14 members in 3 generations of the family, 6 of whom were affected (3 males and 3 females) , demonstrating an autosomal dominant inheritance pattern. Skin lesions were mainly distributed on the face, trunk and limbs, accompanied by special facial features and cardiovascular system abnormalities. A missense mutation c.1632G>T (p.R558L) in the PTPN11 gene was identified in the 4 patients, which resulted in the substitution of arginine by leucine at amino acid position 558. This mutation had not yet been reported previously. No mutation was detected in the PTPN11 gene in the 2 unaffected family members or 100 healthy controls.Conclusion:The missense mutation c.1632G>T in exon 13 of the PTPN11 gene may be the molecular basis for LEOPARD syndrome in this family.

Porcine deltacoronavirus (PDCoV) is a newly emerging enteropathogenic swine coronavirus causing acute diarrhea and vomiting in pigs. The apoptosis of ST cells induced by PDCoV infection was studied in this research. In ST cells, caspase activity assay showed that the activity of caspase 3, caspase 8 and caspase 9 increased significantly with the infection of PDCoV, but not observed in UV irradiated PDCoV-infected cells, indicating that PDCoV infection activated both endogenous and exogenous apoptotic pathways in ST cells, and the induction of apoptosis depended on viral replication. To further investigate the endogenous apoptosis induced by PDCoV, cytochrome C and apoptosis-inducing factors in cytoplasm and mitochondria were detected. Compared with normal cells, the amount of cytochrome C released from mitochondria to cytoplasm increased significantly in PDCoV-infected cells, and the release increased with the prolongation of infection, while the apoptosis-inducing factor was always localized to mitochondria, suggesting that PDCoV induced apoptosis was initiated through caspase-dependent mitochondrial apoptosis pathway by promoting cytochrome C in the mitochondrial membrane gap into the cytosol. In conclusion, this study reveals the mechanism of PDCoV inducing apoptosis.
Animals ; Apoptosis ; Coronavirus ; Coronavirus Infections ; Mitochondria ; Swine ; Swine Diseases

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by genetic alterations with high heterogeneity. Precise subtypes with distinct genomic and/or gene expression patterns have been recently revealed using high-throughput sequencing technology. Most of these profiles are associated with recurrent non-overlapping rearrangements or hotspot point mutations that are analogous to the established subtypes, such as DUX4 rearrangements, MEF2D rearrangements, ZNF384/ZNF362 rearrangements, NUTM1 rearrangements, BCL2/MYC and/or BCL6 rearrangements, ETV6-RUNX1-like gene expression, PAX5alt (diverse PAX5 alterations, including rearrangements, intragenic amplifications, or mutations), and hotspot mutations PAX5 (p.Pro80Arg) with biallelic PAX5 alterations, IKZF1 (p.Asn159Tyr), and ZEB2 (p.His1038Arg). These molecular subtypes could be classified by gene expression patterns with RNA-seq technology. Refined molecular classification greatly improved the treatment strategy. Multiagent therapy regimens, including target inhibitors (e.g., imatinib), immunomodulators, monoclonal antibodies, and chimeric antigen receptor T-cell (CAR-T) therapy, are transforming the clinical practice from chemotherapy drugs to personalized medicine in the field of risk-directed disease management. We provide an update on our knowledge of emerging molecular subtypes and therapeutic targets in BCP-ALL.
B-Lymphocytes ; Humans ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

t(8;21)(q22;q22) acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a high relapse rate in China. Two leukemic myeloblast populations (CD34
Gene Expression ; Granulocyte Precursor Cells ; Humans ; Immunophenotyping ; Leukemia, Myeloid, Acute/genetics* ; Membrane Glycoproteins ; Prognosis ; Proteins ; Proto-Oncogene Proteins c-kit/genetics*

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Humans ; Membrane Proteins/genetics* ; Pituitary Neoplasms/genetics* ; Biomarkers