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Objective:To explore the clinical manifestations and genetic characteristics of Wolf-Hirschhorn syndrome (WHS) to improve the ability of diagnosis and differential diagnosis of the disease.Methods:The clinical features and auxiliary examinations and treatment of a proband with WHS caused by microdeletion of 4p16.3 segment who admitted to the Third Affiliated Hospital of Zhengzhou University in December 2021 were recorded, and whole exome sequencing (WES) of the family was performed. The prognosis was followed up.Results:The female proband, 11 months old, presented with convulsions at the age of 8 months, with the characteristics of heat sensitivity and cluster seizures, and her identical twin sister had a similar medical history. Physical examination found malnutrition, retarded development, special face, prominent forehead, wide nasal bridge, small jaw, precordial murmur and grade 3/6 murmur in the whole period, hyperactivity of P2, and low limb muscle tone. The whole exon and copy number variation (CNV) test of the family revealed that the proband had a 1.99 Mb heterozygous deletion in the chromosome 4p16.3 segment, including WHSC1 (NSD2), WHSC2 (NEFLA) and other genes. Copy number variation sequencing (CNV-Seq) of the proband and her sister showed 1.97 and 1.92 Mb heterozygous deletion of chromosome 4p16.3, respectively. Genealogical analysis by quantitative polymerase chain reaction revealed that the CNV was de novo, and it was determined to be a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines. The proband took sodium valproate orally, and her sister took oral sodium valproate, zonisamide, and levetiracetam successively, and at the same time they received family rehabilitation training. The age at the last follow-up was 1 year and 8 months. Neither of them had convulsions again in the past 3 months, but the developmental delay was obvious. Conclusion:WHS patients may present with growth retardation, epilepsy, Greek warrior helmet-like special face, and congenital heart disease, and may have microdeletions in the chromosome 4p16.3 segment.
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Bacillus cereus belongs to Gram-positive bacteria, which is widely distributed in nature and shows certain pathogenicity. Different B. cereus strains carry different subsets of virulence factors, which directly determine the difference in their pathogenicity. It is therefore important to study the distribution of virulence factors and the biological activity of specific toxins for precise prevention and control of B. cereus infection. In this study, the hemolysin BL triayl was expressed, purified, and characterized. The results showed that the bovine pathogenic B. cereus hemolysin BL could be expressed and purified in the prokaryotic expression system, and the bovine pathogenic B. cereus hemolysin BL showed hemolysis, cytotoxicity, good immunogenicity and certain immune protection in mice. In this study, the recombinant expression of hemolysin BL triayl was achieved, and the biological activity of hemolysin BL of bovine pathogenic ceroid spore was investigated. This study may facilitate further investigating the pathogenic mechanism of B. cereus hemolysin BL and developing a detection method for bovine pathogenic B. cereus disease.
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Cattle , Animals , Mice , Bacterial Proteins/metabolism , Bacillus cereus/metabolism , Hemolysin Proteins/metabolism , Virulence Factors/metabolism , Enterotoxins/metabolismABSTRACT
BACKGROUND@#Fibroblast activation protein (FAP) is one of the surface markers of cancer-associated fibroblasts (CAFs) and is closely related to the malignant characterization of CAFs. SP13786 is a specific micromolecule inhibitor of FAP and this study is to investigate the effects and mechanism of SP13786 on the migration and invasion of A549 cells through regulating exosomes of CAFs.@*METHODS@#CAFs and paracancerous fibroblasts (PTFs) were isolated and subcultured from freshly resected lung adenocarcinoma tissues and paracancerous normal tissues separately. MTT assay was used to detect the proliferation of CAFs incubated by different concentrations of SP13786; PTFs-exo, CAFs-exo and CAFs+SP13786-exo were extracted by polymer precipitation method. The A549 cells were divided into Ctrl group, PTFs group, CAFs group and SP13786 group and each group was incubated with DMEM, PTFs-exo, CAFs-exo and CAFs+SP13786-exo separately. Laser confocal microscope was used to observe the endocytoses of exosomes by A549 cells. The expression of alpha-smooth muscle actin (α-SMA) and FAP in PTFs and CAFs and the expression of E-cadherin, N-cadherin, Slug, Stat3 and P-Stat3 in A549 cells were detected by immunofluorescence, immunohistochemistry and Western blot. The migration and invasion ability of A549 cells were detected by cell scratch and transwell methods.@*RESULTS@#α-SMA and FAP were expressed much higher in CAFs than that in PTFs which indicate that CAFs and PTFs were successfully obtained from lung adenocarcinoma and paracancerous tissues (P0.05). Finally, WP1066 (a specific inhibitor of Stat3) was used to comfirm whether SP13786 could influence EMT of A549 cells by inhibiting Stat3 phosphorylation via CAFs-Exo. The results showed that when the phosphorylation of Stat3 in CAFs group was inhibited by WP1066, SP13786 could not influence the P-Stat3 expression and EMT of A549 cells anymore (P>0.05).@*CONCLUSIONS@#As a specific micromolecule inhibitor of FAP, SP13786 indirectly inhibits the migration and invasion of A549 cells by affecting exosomes of CAFs. The possible mechanism is to inhibit the phosphorylation of Stat3 and thus affect the EMT of A549 cells.
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Objective To investigate the effect of cystatin C (Cys C) on adventitia in rabbit abdominal aorta restenosis after angioplasty and its mechanism.Methods 48 New Zealand white rabbits were randomly divided into injury group (receiving balloon dilation of abdominal aorta),the treatment group (taking Cys C monoclonal antibody therapy) and the control group (receiving femoral artery puncture and catheter sheath without balloon dilation and intervention of Cys C monoclonal antibody injection),and each group had 16 rabbits.Peripheral vein blood was drawn to measure the serum level of cystatin C before and 8 h,1 day,1 week,3 weeks,6 weeks after the operation in all rabbits.After 6 weeks of operation,the abdominal aorta were taken and stained with HE.Vascular morphometry analysis and adventitial cell count were conducted.Smooth muscle actin (SM-actin) and proliferating cell nuclear antigen (PCNA) expressions in the adventitia were observed by immunohistochemical staining.The number of PCNA positive cell in the adventitia was counted and the PCNA proliferation index was calculated.The vascular remodeling index,vascular external elastic lamina area (EELA),internal elastic lamina area (IEIA) were used to evaluate the vascular remodeling and the residual stenosis and vascular cavity area was used to measure the vascular stenosis.Results Plasma Cys C level began to rise at 8h after operation and reached the peak at 1 week after operation,and continuously increased for 5 weeks in injury group,and reached to respectively at 3 weeks and 6 weeks after operation.The Cys C levels were significantly higher in injury group than in the treatment and control groups at different time points (all P＜0.05).There were no significant differences in Cys C levels at different time points between the treatment group and the control group.The injury group showed that the number of PCNA positive cells was higher in injury group than in treatment and control groups,both P＜0.05).Compared with the control group,the vascular luminal area,EELA and IELA were significantly increased (all P＜0.05).After treated with the monoclonal antibody Cys C intervention,the treatment group showed that lumen area,vascular EELA,IELA was significantly decreased (P＜0.05),and the vascular remodeling index and residual stenosis rate were decreased as compared with the injury group (0.871 vs.0.784,33.1％ vs.19.7 ％,both P＜0.05).Correlation analysis showed that Cystatin C level was positively correlated with the vascular lumen area,neointimal area,internal elastic lamina area,external elastic lamina area and the number of PCNA positive cells (r=0.812,0.797,0.876,0.932 and 0.822 respectively,all P＜0.01).Conclusions Plasma Cys C level is increased in rabbit after abdominal aorta balloon injury and has a positive correlation with the severity of arterial stenosis.High Cys C level can induce adventitial fibroblast activation,proliferation,phenotype transformation and migration,and accelerate the processes of atherosclerosis and stenosis.Cys C level is the independent risk factor for abdominal aortic stenosis.
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Objective To assess the relationship between fractional esterification rate of high density lipoprotein cholesterol (FERHDL) and coronary artery disease .Methods The patients were underwent coronary angiography in this hospital in the last three years were collected ,according to the results of coronary angiography ,286 patients were divided into CHD group(n=196) and non-CHD group(control group ,n=90) .And according to the number of pathological coronary artery ,the patients with coronary heart disease were divided into single-vessel subgroup(n=73) ,double vessel lesion subgroup(n=72) ,three branch lesions subgroup (n=51) .The relationship between FERHDL and coronary artery disease were analyzed .Results The FERHDL of CHD group was significantly higher than that in the control group ,the difference was statistically significant (P<0 .05) .It was a tendency that the FERHDL increased with coronary lesions increasing (P<0 .05) .The FERHDL was significant independent correlated with the low density lipoprotein cholesterol b-C(LDLb-C) ,triglycerides(TG) ,high density lipoprotein cholesterol 2-C(HDL2-C) ,high density lipoprotein cholesterol C(HDL-C) .FERHDL was positively correlated with LDLb-C(r=8 .473 ,P=0 .000) ,TG(r=0 .714 ,P=0 .002) and negatively correlated with HDL2-C(r= -0 .692 ,P=0 .024)、HDL-C(r= -0 .829 ,P=0 .008) .Conclusion The value of FERHDL was significantly increased in CHD patients and correlated with the aggravation severity of the CHD .The change of FERHDL was significant correlated with particle size of HDL and LDL particle size .
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<p><b>OBJECTIVE</b>To determine whether the level of serum cardiac troponin T (cTnT) was increased in patients with congestive heart failure (CHF).</p><p><b>METHODS</b>This study consisted of 265 patients with CHF and 75 healthy people. Serum cTnT was measured by electrochemiluminescence immunoassay using an Elecsys 1010 automatic analyzer.</p><p><b>RESULTS</b>cTnT concentration was 0.181 +/- 0.536 ng/mL in CHF patients and 0.003 +/- 0.001 ng/mL in controls (P < 0.001). Patients were categorized according to the levels of heart function and left ventricular ejection fraction (LVEF). In the first group consisting of 105 patients with LVEF </= 35%, cTnT was 0.311 +/- 0.221 ng/mL. In the second group of 106 patients with LVEF > 35%, cTnT was 0.07 +/- 0.0 5 ng/mL (P < 0.01). In patients with NYHA class I, II, III and IV, cTnT values were 0.062 +/- 0.022 ng/mL, 0.113 +/- 0.121 mg/mL, 0.191 +/- 0.231 mg/ml and 0.384 +/- 0.211 mg/mL, respectively (class I vs class II P > 0.05, class II vs class III P < 0.01, class III vs class IV P < 0.01). A negative correlation was observed between serum cTnT concentration and LVEF in 265 patients with CHF (r = -0.493, P < 0.001).</p><p><b>CONCLUSIONS</b>This study shows that the level of serum cTnT is increased in patients with CHF and that the increased level indicates the severity of CHF.</p>