ABSTRACT
Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G > A, p.Gly970Asp in exon 18 and c.1210-3C > G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C > G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C > G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.
Subject(s)
Humans , China , Cystic Fibrosis/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Mutation , Poly T , RNA, Messenger/geneticsABSTRACT
Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in γ-secretase component genes. We and other researchers showed that nicastrin (NCSTN) is the most frequently mutated gene in familial AI. In this study, we generated a keratin 5-Cre-driven epidermis-specific Ncstn conditional knockout mutant in mice. We determined that this mutant recapitulated the major phenotypes of AI, including hyperkeratosis of hair follicles and inflammation. In Ncstn;K5-Cre mice, the IL-36a expression level markedly increased starting from postnatal day 0 (P0), and this increase occurred much earlier than those of TNF-α, IL-23A, IL-1β, and TLR4. RNA-Seq analysis indicated that Sprr2d, a member of the small proline-rich protein 2 family, in the skin tissues of the Ncstn;K5-Cre mice was also upregulated on P0. Quantitative reverse-transcription polymerase chain reaction showed that other Sprr2 genes had a similar expression pattern. Our findings suggested that IL-36a might be a key inflammatory cytokine in the pathophysiology of AI and involved in the malfunction of the skin barrier in the pathogenesis of AI.
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Objective To analyze the clinical and laboratory characteristics of the ischemic stroke in patients with non-valvular atrial fibrillation (AF), and to provide evidence for the prevention of ischemic stroke. Methods A total of 198 patients with ischemic stroke were chosen and divided into two groups:with AF (71 patients)/and without AF (127 patients) groups. Clinical data and biochemical markers were collected and compared in two groups. CHADS2 and CHA2DS2-VASc score systems were used to determine the risk levels in patients with AF. Finally, related risk factors of ischemic stroke with AF were determined and analyzed. Results The values of age, length of hospital stay, the hypertention history, heart rate and plasma homocysteine (Hcy) were significantly higher in the with-AF group than those in the without-AF group ( P <0.05). The levels of total cholesterol (TC), triglyceride (TG) and very low density lipoprotein cholesterol (VLDL-C) were sig?nificantly lower in the with-AF group than those of the without-AF group (P<0.05). CHA2DS2-VASc scores reached to the moderate-to-high risk level in the with-AF group. Multiple-factor logistic regression analysis showed that age and heart rate were the independent risk factors of the ischemic stroke in patients with non-valvular AF. ROC analysis indicated that age (AUC=0.761, cut-off point=72.50 years old) and heart rate (AUC=0.612, cut-off point=76.50 bit/min) had predictive and di?agnostic value for the ischemic stroke in patients with non-valvular AF. The age of these patients had the best sensitivity (70.4%) and specifity (71.1%), and the cut-off point of which was 72.50 years old. Conclusion The characteristics of isch?emic stroke in patients with non-valvular AF includes older age, faster heart rate, higher CHA2DS2-VASc scores and higher Hcy level.
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Objective:To investigate the changes of left ventricular mass index(LVMI),plasma brain natriuretic peptide (BNP),interJeukin-6(IL-6)and interleukin-10(IL-10)in patients with congestive heart failure(CHF),and their values in risk stratification and prognostic evaluation of CHF thereof.Methods:Ninety-five patients with CHF in accordance with 2001ACC/AHA guidelines were enrolled and stratified as stage A(n=21),B(n=23),C(n=31)and D(n=20).The levels of plasma BNP,IL-6 and IL-10 were measured and compaired with those in 20 healthy subjects(control group).The patients were followed up every three months in two years.The end point was the rehospitalization and the cardiac death.Results:(1)The level of LVMI increased early in patients with CHF at stage B.(2)The plasma BNP levels were initially elevated in CHF patients at stage B,and the concentrations of BNP closely paralleled disease severity.(3)The levels of plasma IL-6 and IL-10 were increased,and the ratio of IL-10/IL-6 was decreased,with the progression of CHF at stage C and D.The plasma BNP level was positively correlated with the levels of IL-6 and IL-10.(4)The new CHF stratification was surperior to NYHA functional classification in regard to CHF prognosis prediction.(5)Multivariate COX regression analysis showed the levels of BNP and IL-6 were the independent risk factors in prognostic evaluation(P＜0.01,P=0.026).(6)Patients in high-risk groups stratified by the combination of BNP and stage classification had obviously higher end point events rate.Conclusion:(1)LVMI was a better marker for the evaluation of left ventrieular remodeling.(2)The intrinsic mechanism of CHF progression was inflammatory reaction deterioration.(3)BNP was a good marker in predicting onset and prognosis of CHF.The combination of BNP and the stage classification could improve the prognostic evaluation in patients with CHF.
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Objective:To evaluate the changes of the left atrial systolic function in patients with acute myocardial infarction(AMI)using quantitative tissue velocity imaging(QTVI).Methods:The systolic velocities of the middle of left atrial lateral wall,anterior wall,inferior wall and atrial septum were measured with QTV1 in 45 patients with AMI.The left atrial volume and active atrial emptying fraction(AA-EF)were measured using single-plane Simpson method.Results:(1)Compared with the control group(30 normal subjects),the diameter and volume of the left atrium,as well as AA-EF,increased obviously in patients with AMI(P ＜ 0.01).(2)Compared with the control group,the systolic velocities of the middle of left atrial lateral wall,anterior wall,inferior wall and atrial septum,as well as the average value,increased significantly in patients with AMI (P ＜ 0.05 or P ＜ 0.01).In addition,the average value of left atrial systolic velocity was closely correlated with AA-EF(r=-0.906,tr=14.001,P ＜ 0.01).Conclusion:QTVI could be used to evaluate the left atrial systolic function accurately in patients with AMI.
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Objective To summarize the experiences in clinical diagnosis and surgical treatment of chest cancers invading the superior vena cava (SVC). Method Retrospective study of 12 cases with chest cancers invading the SVC, SVC and innominate vein were reconstructed with prosthesis in 3 cases, the side wall of the SVC was excised and repaired in 9 cases. Results Complete resection was performed in 10cases,2 cases had incomplete resection. There was no death associated with operation in these patients. All patients were followed up for 1 - 7 years after operation,and 3 cases were lost to follow up,5 of remaining 9cases were dead because of relapse and metastasis, their median survival time was 8 months,other 4 cases lived, their median survival time was 42 months. Conclusions Patients with chest cancers invading the SVC should have surgical treatment of not only tumor resection but also the vessel reconstruction,the prognosis would be better than without surgical treatment. These patients have a high quality of life and live with long-term survival.
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Objective:To observe the correlation of platelet activation and the inflammatory factors in patients with coronary heart disease (CHD).Methods:A total of 150 patients with CHD were divided into three groups according to the guideline of ACC/AHA:Stable angina pectoris (SAP) group (n=47,aspirin 100 mg/d); Unstable angina pectoris(UAP) group (n=50,aspirin 100 mg/d+Dalteparin 5000 U Q12 h); Acute myocardial infarction (AMI) group (n=53,aspirin 100 mg/d+Dalteparin 5000 U Q12 h+Plavix 75 mg/d).53 healthy adults served as the Control group.The fast blood sugar,lipid,platelet count,platelet aggregation of plasma,fibrinogen,high sensitivity C reactive protein (hs-CRP) of plasma,and 11-dehydro thromboxane B_2 (11-DH-TXB_2) of urine were detected upon patients' admission.Results:The level of plasma hs-CRP in groups of SAP,UAP and AMI(4.25±2.95 mg/l,7.61±6.11 mg/l,15.46±8.22 mg/l)were significantly higher than that in Control group(2.07±1.28 mg/l,P<0.05).The max rate of platelet aggregation induced by ADP in groups of UAP and AMI were significantly higher than that in Control and SAP groups(74.35±8.91%,73.88±8.35% vs.66.22±7.51%,68.67±6.87%,P<0.05).There were significant differences in the max rate of platelet aggregation induced by arachidonic acid (AA) and 11-DH-TXB_2 of urine in different groups (P<0.05).The level of plasma hs-CRP in all patients with CHD were significantly positively correlated with the max rate of platelet aggregation induced by ADP (r=0.473,P=0.000),AA(r=0.434,P=0.000) and 11-DH-TXB_2 of urine (r=0.554,P=0.000).Conclusion:There were significant relationship between the levels of plasma hs-CRP,11-DH-TXB_2 and the max rate of platelet aggregation,which indicating inflammation might induce platelet aggregation in CHD patients.
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Objective: To investigate the effect of medication on left ventricular myocardial matrix remodeling in neuroendocrine hypertensive rats and the mechanism and inhibitive method thereof. Methods: A neuroendocrine hypertensive model was established with adult Wistar rat. A total of 34 rats were randomly divided into four groups: parzosin (Hα), cilazapril (Hace), pentoxifylline(Hptx) and hypertensive control group(Hc). Ten normal-tensive Wistar rats were used as normal control (Nc). The systemic blood pressure, serum procollagen type Ⅲ level, serum TNF-α level, collagen volume fraction(CVF) were detected. Results: In Hace group, systolic pressure, left ventricular weight, the levels of serum procollagen type III and TNF-α were all reduced obviously compared to those in Hc group(P < 0.05). In Hα group, the systolic pressure and left ventricular weight were reduced obviously compared to those in Hc group(P < 0.05), however, the levels of serum procollagen type III and TNF-α were higher than those of Nc group(P < 0.05). In group Hptx, the systolic pressure and left ventricular weight were not decreased, while the levels of serum procollagen typeⅢ,TNF-α and CVF were reduced to normal levels. Conclusion:The angiotensin coverting enzyme inhibitor is the effective agent to reverse myocardial fibrosis, which can be achieved mostly by the inhibition of AngⅡ. Pentoxifylline may inhibit and reverse myocardial fibrosis which correlated with inhibiting TNF-α.