Granulomatosis with polyangiitis with nasal symptoms as the first clinical manifestation: clinical analysis of 18 cases / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze and summarize the diagnosis, treatment and prognosis of granulomatosis with polyangiitis (GPA) with nasal symptoms as the first clinical manifestation. Methods: The data of 18 patients of GPA with nasal mucosal symptoms as the first clinical manifestation from the Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University between 2005 and 2019 was collected, including 8 males and 10 females, aged from 5 to 68 years. Nasal endoscopy, imaging examination, laboratory examination, immunological and histopathological examination of nasal mucosa were completed. All patients were treated with glucocorticoid combined with cyclophosphamide and were followed up for 2 to 15 years. Descriptive statistical method was used for analysis. Results: All the 18 patients had the nasal mucosal symptoms as the first clinical manifestation, including nasal obstruction, running nose and epistaxis. Nasal endoscopy showed swelling, erosion, scab and bleeding of nasal mucosa, and 6 cases had nasal septal perforation. Nasal sinus CT scan showed high density shadow of sinus, as well as hyperostosis and osteosclerosis. CT imaging features of pulmonary showed nodular lesion or patchy infiltration in 12 patients and cavitation was found in 6 cases. Laboratory results showed that 13 cases were positive for anti-neutrophil cytoplasmic antibodies (ANCA), and 5 cases were negative. During follow-up period, thirteen patients were symptomatic controlled and survived; two patients died of disease progression; one patient gave up treatment and died; two patients were lost to follow-up. Conclusions: Nasal symptoms are the first clinical manifestation of GPA. Early diagnosis and early treatment with glucocorticoid combined with cyclophosphamide can effectively improve the survival rate.

Serum Metabolomic Indicates Potential Biomarkers and Metabolic Pathways of Pediatric Kashin-Beck Disease / 生物医学与环境科学（英文）

Objective@#To explore potential serum biomarkers of children with Kashin-Beck Disease (KBD) and the metabolic pathways to which the biomarkers belong.@*Methods@#A two-stage metabolomic study was employed. The discovery cohort included 56 patients, 51 internal controls, and 50 external controls. The metabolites were determined by HPLC-(Q-TOF)-MS and confirmed by Human Metabolome Databases (HMDB) and Metlin databases. MetaboAnalyst 3.0 and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used to analyze the metabolic pathways of the candidate metabolites. The use of HPLC-(Q-TRAP)-MS enabled quantitative detection of the target metabolites which were chosen using the discovery study and verified in another independent verification cohort of 31 patients, 41 internal controls, and 50 external controls.@*Results@#Eight candidate metabolites were identified out in the discovery study, namely kynurenic acid, N-α-acetylarginine, 6-hydroxymelatonin, sphinganine, ceramide, sphingosine-1P, spermidine, and glycine. These metabolites exist in sphingolipid, glutathione, and tryptophan metabolic pathways. In the second-stage study, five candidate metabolites were validated, including kynurenic acid, N-α-acetylarginine, sphinganine, spermidine, and sphingosine-1P. Except for spermidine, all substances exhibited low expression in the case group compared with the external control group, and the difference in levels of sphinganine, spermidine, and sphingosine-1P was statistically significant.@*Conclusion@#The direction of change of levels of sphinganine, spermidine, and sphingosine-1P in the two-stage study cohorts was completely consistent, and the differences were statistically significant. Therefore, these substances can be used as potential biomarkers of KBD. Furthermore, these results raise the possibility that sphingolipid metabolic pathways may be closely related to KBD.

The role of Tif1γ on apoptosis of pancreatic cancer cells / 复旦学报（医学版）

Objective To investigate the effect of transcriptional internediary factor 1 gamma (Tif1γ)and its signal pathway related proteinson apoptosis of human pancreatic cancer cell line Capan-1 treated with either gemcitabine (GEM) or raltitrexed (RTX).Methods Capan-1 cells were treated with GEM of 559 μmol/L or RTX of 0.86 μmol/L for 36 h.The cell apoptosis of Capan-1 was determined using flow cytometry.Protein levels of Tif1γ,TGF-β1,Smad3,p-Smad3,Smad4,Bcl2,BAX and Caspase3 in Capan-1 cells were determined by Western blot.Results The late apoptosis and death ratio after RTX treatment were 28.7％ ± 5.1％ and 3.7％ ± 0.5％,respectively,showing significant difference from that after GEM treatment or untreated control group (P＜0.01).The results of Western blot showed that the relative protein levels of Tif1 γ,TGF-β1,p-Smad3,BAX and Caspase3 in Capan-1 cells were increased in RTX group compared with those in GEM group or control group (P＜0.05).The relative protein levels of Smad4 and the Bcl2/Bax ratio were decreased in RTX group compared with those in GEM group or control group (P＜0.05).Conclusions Increased level of Til1γ by RTX treatment resulted in decreased level of Smad4 to regulate the balance of Bcl2/Bax,increased Caspase3 and increased apoptosis in Capan-1 cells.

Relationship between apolipoprotein E, D10S1225 polymorphisms and late-onset Alzheimer's disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There were some papers published in the Jonrnal of Science, December 2000 suggesting that one or more important susceptibility genes for late onset Alzheimer's disease (LOAD) were located on the long arm of chromosome 10. Linkage analysis showed maximum lod score close to D10S1225 loci, which indicated the loci might contribute to the etiology of Alzheimer's disease (AD).</p><p><b>METHODS</b>Fifty-nine LOAD patients and 107 controls were recruited. Apolipoprotein E (ApoE) genotypes were determined by reverse dot blotting hybridization assay. The D10S1225 was genotyped by 12% nondenaturing polyacrylamide gels electrophoresis and analyzed by silver staining. Statistical analysis was used to compare genotype and allele distributions between LOAD group and control group for ApoE and D10S1225 polymorphisms.</p><p><b>RESULTS</b>ApoE epsilon 4 was significantly higher in LOAD group in comparison with the control group (chi(2) = 6.530, P = 0.011). Seven different alleles of D10S1225 have been identified. The length of these gene fragments were 178 bp, 181 bp, 184 bp, 187 bp, 190 bp, 193 bp, and 196 bp, respectively. A total of 21 different genotypes were observed. There was no relationship between D10S1225 polymorphism and LOAD (chi(2) = 4.488, P > 0.05). Conclusion This study suggests that ApoE epsilon 4 is a risk factor for LOAD, however, the results indicated that there is not any possible linkage for disequilibria with a nearby AD risk gene near D10S1225.</p>

Preparation and purification of siRNA targeting a proliferation-inducing ligand of pancreatic cancer cell line / 第二军医大学学报

Objective:To prepare and purify siRNA targeting a proliferation-inducing ligand targeted(APRIL-siRNA),so as to provxde a basis for studying the role of APRIL in human pancreatic cancer.Methods:pET-22b-APRIL was constructed to express APRIL dsRNA of human pancreatic cancer cell line CFPAC-1 in E.coli and the product was purified by chromatography using CF-11 column.APRIL dsRNA was digested by RNaseⅢto prepare APRIL siRNA,then the reaction mixture was loaded onto a DEAE ion exchange chromatography to remove RNaseⅢfrom oligonucleotides,and size exclusion chromatography was used to purify 21 bp siRNA.The purified APRIL siRNA was used to transfect Chinese hamster ovary(CHO)cells and the expression of APRIL in CHO cells was observed under fluorescence microscope Results:APRIL dsRNA was successfully expressed in E.coli after IPTG induction and was purified by CF-11 column.dsRNA was hydrolyzed with RNaseⅢand was purified by DEAE ion exchange chromatography and size exclusion chromatography.15% nondenaturing PAGE and 12% SDS- PAGE confirmed that RNaseⅢwas removed from oligonucleotides and 21 bp siRNA was purified with size exclusion chromatography.It was also found that APRIL siRNA obviously depressed APRIL expression in CHO cells.Conclusion:We have successfully constructed APRIL siRNA targeting APRIL gene of CFPAC-1 cells with in vitro transcription,which provides a basis for knock-down of APRIL gene in CFPAC-1 cells.