Analysis of F12 gene variants and molecular mechanisms in patients with coagulation factor Ⅻ deficiency / 中华医学遗传学杂志

OBJECTIVE@#To analyze the sequence of the F12 gene and molecular mechanism for 20 patients with coagulation factor Ⅻ (FⅫ) deficiency.@*METHODS@#The patients were selected from the outpatient department of the Second Hospital of Shanxi Medical University from July 2020 to January 2022. The activity of coagulation factor Ⅷ (FⅧ:C), factor Ⅸ (FⅨ:C), factor Ⅺ (FⅪ:C) and factor Ⅻ (FⅫ:C) were determined by using a one-stage clotting assay. All exons and 5' and 3' UTR of the F12 gene were analyzed by Sanger sequencing to detect the potential variants. Bioinformatic software was used to predict the pathogenicity of the variants, conservation of amino acids, and protein models.@*RESULTS@#The FⅫ:C of the 20 patients has ranged from 0.07% to 20.10%, which was far below the reference values, whilst the other coagulation indexes were all normal. Sanger sequencing has identified genetic variants in 10 patients, including 4 with missense variants [c.820C>T (p.Arg274Cys), c.1561G>A (p.Glu521Lys), c.181T>C (p.Cys61Arg) and c.566.G>C (p.Cys189Ser)], 4 deletional variants c.303_304delCA(p.His101GlnfsX36), 1 insertional variant c.1093_1094insC (p.Lys365GlnfsX69) and 1 nonsense variant c.1763C>A (p.Ser588*). The remaining 10 patients only harbored the 46C/T variant. The heterozygous c.820C>T(p.Arg274Cys) missense variant in patient 1 and the homozygous c.1763C>A (p.Ser588*) nonsense variant in patient 2 were not included in the ClinVar and the Human Gene Mutation Database. Bioinformatic analysis predicted that both variants were pathogenic, and the corresponding amino acids are highly conserved. The protein prediction models suggested that the c.820C>T (p.Arg274Cys) variant may affect the stability of the secondary structure of FⅫ protein by disrupting the original hydrogen bonding force and truncating the side chain, leading to changes in the vital domain. c.1763C>A (p.Ser588*) may produce a truncated C-terminus which may alter the spatial conformation of the protein domain and affect the serine protease cleavage site, resulting in extremely reduced FⅫ:C.@*CONCLUSION@#Among individuals with low low FⅫ:C detected by one-stage clotting assay, 50% have harbored variants of the F12 gene, among which the c.820C>T and c.1763C>A were novel variants underlying the reduced coagulating factor FⅫ.

Relationship between deceleration capacity of heart rate and ventricular arrhythmia / 心血管康复医学杂志

Objective:To analyze deceleration capacity of heart rate (DC) in patients with ventricular arrhythmia , and explore its predictive value for ventricular arrhythmia .Methods :Dynamic electrocardiogram (DCG) data of outpatients and inpatients ,who were treated in our hospital from Jan 2012 to Jul 2015 ,were retrospectively ana‐lyzed .A total of 41 rehabilitation patients with ventricular tachycardia (VT) directly detected by DCG were treated as VT group ,another 37 cases with similar general data and non‐tachycardia were enrolled as non‐tachycardia group in the same period .DCG was used to measure and calculate DC in all subjects , DC indexes were compared between two groups .Results:DC<4.5 ms was regarded as abnormal and DC<2.5 ms was regarded as significantly abnor‐mal .Compared with non-tachycardia group ,DC significantly reduced [ (8.72 ± 1.78) ms vs .(4.01 ± 1.90) ms] , P<0.01 ;there were significant rise in abnormal DC rate (5.41% vs .51.22% ) and significant abnormal DC rate (0 vs .29.27% ) in VT group , P<0.01 both .Conclusion:Detection rate of abnormal DC is high in VT patients .DC measurement is helpful for predicting ventricular arrhythmia and sudden cardiac death .

The relationship between expression of Her-2 and human papillomavirus and clinicopathological features in esophageal and stomach multiple primary cancers / 肿瘤研究与临床

Objective To analyze the relationship between expression of Her-2 protein and the infection of human papillomavirus (HPV) and clinicopathological features in upper gastrointestinal multiple primary cancers, and to explore the relationship between the different histological malignancies in a single-system. Methods 39 patients were primary esophageal squamous cell carcinoma and gastric/cardia adenocarcinoma. By using immunohistochemistry (IHC) methods, the expression of Her-2 protein in 39 cases of multiple primary cancers specimens were examined, and by using insitu hybridization (ISH) technology, the infection of HPV in the same ones were detected. Results The over-expression of Her-2 protein in esophageal squamous cell carcinoma was not significantly relative to the degree of differentiation, the depth of penetration, the lymph node metastasis and the patientsˊage and gender (P> 0.05). The over-expression of Her-2 protein in gastric adenocarcinoma was closely correlated to the invasion depth and lymph node metastasis (P 0.05). The infection of HPV in esophageal squamous cell carcinoma and gastric adenocarcinoma was not significantly relative to the degree of differentiation, the depth of penetration,the lymph node metastasis, and the age and gender of the patients (P> 0.05). In the upper gastrointestinal multiple primary cancers, the Her-2 protein over-expression had the consistency (κ= 0.56, P< 0.05). Meanwhile, the HPV-DNA expression also had the consistency (κ=0.80, P<0.05). Conclusion Both Her-2 protein and HPV expression show the consistency in upper gastrointestinal multiple primary cancers,which suggests that Her-2 protein and HPV may be the common oncogenic factors for both esophageal squamous cell carcinoma and gastric adenocarcinoma.

Feature analysis of Lorenz plots of dual parasystole / 心血管康复医学杂志

Objective:To observe the feature of Lorenz plots of dual parasystole ,and explore its differential diagnosis significance .Methods :Lorenz plot data of seven patients diagnosed as dual parasystole was retrospectively analyzed . They were compared with those of single source premature beat ,dual premature beat and single source parasystole . Results :All case data were divided into six groups (seven cases in each group) ,its features were :group 1 [ (single source atrial premature beat (APB)] ,plots were characterized with three distribution and sinus rhythm located on 45° line ;group 2 (dual source APB) were five distribution with the same sinus rhythm location ,the points set before and after premature were located on its two sides ,the plot was symmetry ,slopes of line B were within 0~1 in group 1 and 2 and its slopes were no significant difference (P>0.05);group 3 was single source ventricular premature beat (VPB) ,show four distribution pattern ,sinus rhythm was located on 45° line ,the points set before and after prema-ture were almost parallel to X and Y axis ;group 4 ( dual source VPB) were in six distribution with the same sinus rhythm location ,its difference with single source VPB was the points set before and after premature were symme-try;slopes of line B all trends to 0 in group 3 and 4 ,their slope also no significant difference (P>0.05);Group 5 (single source parasystole ) was characterized as four distribution vertical to 45° line ,premature point set was vertical to 45° line ,point set before and after premature were vertical to axis X and Y respectively ;group 6 (dual parasysto-le) were seven distribution vertical to 45° line ,were similar to that of single source parasystole ,the difference was figure of group 6 was dual distribution ;slopes of line B were close to ∞ in group 5 and 6 ,and its difference were no significant (P>0.05) .The line B slopes in group 5 and 6 were significantly higher than those of group 1&2 [ (∞ ) vs .(4.78 ± 0.19)] ,and those of group 1&2 were significantly higher than those of group 3&4 (0.36 ± 0.06) ,P<0.01 all .Conclusion:There are significant difference in Lorenz plot features among single (dual) source atrial/ven-tricular premature beats ,single source parasystole and dual parasystole .Lorenz plot is helpful to differential diagno-sis of parasystole .

Clinical and pathological study on retroperitoneal angiomyolipoma / 中国医师进修杂志

Objective To analyze the clinical and pathological features,diagnosis and differential diagnosis,treatment and prognosis of retroperitoneal angiomyolipoma (RAML).Methods The clinical data of 3 cases diagnosed with RAML,during 2012 to 2014 were studied.The expression of AE1/AE3,Vimentin,HMB45,Melan-A,S-100,SMA,CD10,CD34 and Ki-67 were detected by full automatic immunohistochemistry instrument.Four cases were followed up,the relevant published articles were reviewed as well.Results Four patients contained 3 female and 1 male.Three patients of them were found because of abdominal pain and discomfort symptom,1 case was found on examination.All of them more than 10 cm,and the boundary was not clear.Tumor resection + nephrectomy were used for treatment.Macroscopically,the tumor were consisted of fat,muscle cells and thick walled blood vessels.But they had different proportion.Immunohistochemically:AE1/AE3 negative; Vimentin,HMB45,Melan-A,SMA were positive; S-100 was positive in 3 cases and negative in 1 case; Ki-67 proliferation index were ＜5％.Conclusions The RAML is a rare benign retroperitoneal stromal tumor,which has a complex and diverse pathological organizations.The diagnosis can be made by special immune phenotype in combination with microscopic appearance.