Congenital heart disease is caused by abnormal embryonic heart development.According to the research findings of developmental biology,different heart cells must be strictly regulated to ensure proper cell location and development.In the process of heart development,transcription factors play an important role in the regulation of gene expression.Zinc finger transcription factor GATA-6,an early indicator of myocardial cell development,is currently regarded as main candidate gene involved in the pathogenesis of congenital heart disease.GATA-6 gene mutations lead to changes in transcriptional activity of the gene product,which together with other relevant factors may play a role in the pathogenesis of congenital heart disease.

Objective To understand the relationship between GATA -4,-5,-6 gene mutations and con-genital heart disease(CHD),and to provide grounds for early prevention and genetic counseling of children with CHD. Methods GATA -4,-5,-6 coding regions exons and the flanking intron sequences in 1 98 CHD patients were screened,including 66 cases of the ventricular septal defects,84 cases of the atrial septal defects,and 48 cases of the nonsyndromic conotruncal heart defects patients.A total of 300 healthy subjects were selected as controls.The acquired sequences were aligned with which those publicized in GenBank by the aid of program BLAST.All exons and bilateral partial intron -exon boundaries of GATA -4,-5,-6 genes were amplified by the polymerase chain reaction (PCR). The PCR products were purified and directly sequenced by automatic DNA sequence equipment.The acquired GATA -4,-5,-6 gene sequences were compared with GenBank standard gene sequences with the aid of program BLAST. Results A heterozygous missense mutation in the GATA -4 gene was identified in a ventricular septal defect patient and a persistent truncus arteriosus patient.The mutation was located in c.799G >A(p.V267M)in exon 4 of GATA -4. Multiple aligenment of GATA -4 proteins across species demonstrated that altered amino acid was highly conserved. Transcription factor GATA -5,-6 screening showed no mutations in children with CHD in this study.Conclusions Transcription factor GATA -4 gene mutation may be associated with the occurrence of CHD.Transcription factor GATA -4 gene may be susceptible gene in human CHD.

Objective To investigate the expression levels and clinical significance of (forkhead box Q1) FOXQ1 and E-cadherin in esophageal squamous cell carcinoma (ESCC). Methods Expression levels of FOXQ1 and E-cadherin were in ESCC tissues (ESCC group, n=42) and adjacent normal esophageal tissues (control group, n=42) were detected using im?munohistochemistry. Correlations of FOXQ1 and E-cadherin expressions with clinical pathological parameters and progno?sis were analyzed between two groups. Results The expression level of FOXQ1 was significantly higher in ESCC group than that in control group(64.29% vs 28.57%,χ2=5.384,P<0.05). The expression level of E-cadherin was significantly lower in ESCC group than that incontrol group(52.38%vs 90.48%,χ2=7.691,P<0.05). There were significant differences in FOXQ1 expressions between different TNM stages and whether lymph node metastasis is involved within ESCC group. There were significant differences in expression of E-cadherin between different tumor differentiation, depth of invasion, TNM stage and whether lymph node metastasis is involved within ESCC group. The expression of FOXQ1 was negatively cor?related with E-cadherin in ESCC (r=-0.412, P<0.05). The 5-year survival rates were significantly lower with high expres?sion of FOXQ1 or with low expression of FOXQ1(18.52%vs 66.67%,χ2=9.737,P<0.05). The 5-year survival rates were significantly higher with high expression of E-cadherinor low expression of E-cadherin(59.09%vs 10.00%,χ2=10.996,P<0.05). A multivariate Cox's proportional hazard regression analysis indicated that high FOXQ1 expression, low E-cadherin expression and lymph node metastasis were independent prognostic factors for ESCC. Conclusion The expression of FOXQ1 and E-cadherin showed a good correlation with ESCC. And examining expressions of both FOXQ1 and E-cadherin in ESCC may have practical values in estimating the prognosis of ESCC and directing future treatment .

Objectives To explore the clinical symptoms, therapy and prognosis of tachycardia-induced cardiomyopathy (TIC) in children. Methods Clinical data of 22 children with TIC from July 2007 to July 2012 were retrospectively analyzed. Results TIC was mostly seen in male infants and 81.82%of TIC was caused by atrial arrhythmias. The clinical symptom relieved after arrhythmia and ventricular rates were under control with average effective treatment time of (14.00 ± 8.20) days. Ten patients had tachycardia recurrence, 7 of them had atrial arrhythmia and their clinical symptoms were improved after treatment;while 3 of them showed longer time of therapy with average treatment time of (19.50±8.40) days (P<0.05). Five children underwent radiofrequency ablation before school age and got good therapeutic effect. The post-treatment echocardiographic parameters showed cardiac function of TIC children was significantly improved after treatment, including left ventricular end-diastolic diameter index, left ventricular end-systolic diameter index, left ventricular ejection fraction and shortening score (all P<0.05). Conclusions Childhood TIC is a reversible myocardial dysfunction and its prognosis is good. TIC can be induced by various types of tachyarrhythmias and normally by atrial arrhythmia. The preferred treatment of TIC is administration of antiarrhythmic drugs but radiofrequency ablation is needed to ventricular arrhythmias induced TIC.

In recent years, the management of respiratory diseases related to preterm birth has received extensive attention.In 2021, the American Thoracic Society brought together multidisciplinary experts in respiratory, neonato-logy, otolaryngology, sleep medicine, radiology and nursing specialties to develop Guidelines for outpatient respiratory management in infants, children, and adolescents with post-preterm respiratory disease (hereinafter referred to as the " Guideline" ), aiming to provide evidence-based medical evidence for standardized outpatient management of respiratory diseases associated with preterm birth at different ages.The Guideline was interpreted and summarized so that pediatric clinicians could correctly diagnose and treat these diseases, and understand and implement standardized outpatient management on the basis of evidence.

OBJECTIVETo investigate the value of mediastinoscopy in diagnosis of the thoracic diseases and the determination of the operative indication.

METHODSFrom 1979 to 2000, 165 patients were given mediastinoscopy by local infiltration anesthesia (rare cases with additional vein bacic anesthesia). The exploration and biopsy were given to the neoplasms and lymph nodes around the trachea through the pretracheal interstice.

RESULTSThe diagnosis of 125 patients by mediastinoscopy accorded with the pathological diagnosis and that of 21 patients was not accorded with the pathology. The rate of definitive diagnosis was 85.6% (125/146). The other 19 cases were not included into the ground because 11 cases were not given definitive diagnosis and 8 cases with lung cancer were not be performed operation although the results of mediastinoscopy were negative. Twenty patients with lung cancer which had metastasis in the mediastium and 7 patients with malignant lymphadenoma avoided exploratory thoracotomy.

CONCLUSIONThe mediastinoscopy is a effective examinative method to the disease involving the lymph nodes in the mediastinum and the thoracic disease closing on the mediastinum. The mediastinoscopy in appropriate especially to the simple enlargement of lymph node in the mediastinum that is not given definitive diagnosis. The cases with lung cancer accompanied enlargement of lymph node in the mediastinum and that with tumors in the mediastinum may choose the mediastinoscopy.

Adolescent ; Adult ; Aged ; Female ; Humans ; Lung Neoplasms ; diagnosis ; Lymph Nodes ; pathology ; Male ; Mediastinal Neoplasms ; diagnosis ; Mediastinoscopy ; Middle Aged ; Thoracic Diseases ; diagnosis

Objective: To explore the molecular and genetic mechanism of transcription factor GATA-6 in nonsyndromic conotruncal defect (CTD) in order to provide evidence for early prevention and inheritance consultation of CTD. Methods: A total of 32 cases of patients with nonsyndromic CTD and 100 healthy individuals were enrolled in the study.A total of 7 exons and bilateral partial intron-exon boundaries of GATA-6 were amplified by means of polymerase chain reaction (PCR). The PCR products were purified and directly sequenced by using an ABI Genetic Analyzer 3100 Automatic DNA sequence equipment.The acquired GATA-6 gene sequence was compared with standard gene sequence published in National Center for Biotechnology Information database, as well as the healthy control group to observe the GATA-6 gene mutations.The mutations were introduced into pcDNA3.1(+ ) by site-directed mutagenesis PCR on the basis of pcDNA3.1(+ )-GATA-6 in order to generate the GATA6-G245R mutant constructs.Wild type GATA-6, GATA-6-G245R and atrial natriuretic factor-luciferase(ANF-luciferase) were cotransfected into HEK 293T cells in vitro, and the CMV-LacZ were cotransfected as internal reference.Luciferase and galactosidase activity were measured by using luminometer 24 h after transfection and detected in the downstream ANF-luciferase reporter gene. Results: A heterozygous missense mutation in the GATA-6 gene was identified in a patient with double outlets of the right ventricle.The mutation was located in Gly245Arg(G245R) in exon 2 of GATA-6.The mutation of pcDNA3.1(+ )-GATA-6 expression vectors were successfully constructed.Through the detection of luciferase reporter gene activity, it was found that GATA-6-G245R and wild-type GATA-6 decreased by 41.3%, and the comparison between them was statistically significant (P<0.001). Conclusions Transcription factor GATA-6 gene mutation is associated with the occurrence of nonsyndromic CTD.Transcription factor GATA-6 gene may be susceptible gene in human nonsyndromic CTD.

Purpose: The causal relationship between the incidence and prognosis of chronic kidney disease (CKD) and serum testosterone levels in patients is not yet fully understood. This study aims to use the National Health and Nutrition Examination Survey (NHANES), a large-scale nationally representative sample, to investigate the relationship between CKD and testosterone. Materials and Methods: This study included six NHANES cycles for linear regression analysis, verified by multiple imputation methods. Stratified analysis and subgroup analysis were used to demonstrate the stability of CKD’s effect on testosterone. Furthermore, we used Kaplan-Meier plots and log-rank tests to evaluate differences in survival rates between CKD male patients with low and normal levels of testosterone. Results: From a total of 71,163 subjects, the cohort selected 28,663 eligible participants. Results showed that CKD patients had testosterone levels 28.423 ng/mL (24.762, 32.083) lower than non-CKD patients. The results of multiple imputations (β=27.700, 95% confidence interval: 23.427, 31.974) were consistent with those of linear regression analysis, and the numerical match was good. Stratified regression analysis, and subgroup analysis results showed that CKD had a significant impact on testosterone at different dimensions. Kaplan-Meier plots showed significantly reduced survival rates in low testosterone CKD male patients (p<0.0001). Conclusions The results of this big data analysis suggest that there may be a two-way risk between low levels of testosterone and CKD. The testosterone levels of CKD patients were significantly lower than those of the non-CKD population, and CKD patients with low testosterone levels had poorer prognoses. These results suggest that correcting testosterone levels in a timely manner can have preventive and therapeutic effects on the progression of CKD.

BACKGROUNDTo explore the perioperative changes of T subsets and NK cell and analyze the related factors in patients with lung cancer.

METHODSThe T subsets and NK cell from peripheral blood of 60 patients with lung cancer, 15 patients with lung benign tumor and 15 healthy people were detected by immunofluorescence. These indexes of the patients with lung cancer were detected also at postoperative 2nd, 7th, 14th and 28th days.

RESULTS1.There were significant differences in the indexes between the lung cancer group and the groups of lung benign tumor and normal people except for CD8+ (P < 0.05). 2.At postoperative 2nd day CD3+, CD4+, CD4+/CD8+ and NK cell of the patients with lung cancer were decreased and CD8+ was increased significantly than those before operation (P < 0.05). During postoperative 1 to 2 weeks, all indexes had recovered basically to the preoperative level. At postoperative 28th day, CD3+, CD4+ , CD4+/CD8+ and NK cell were increased and CD8+ was decreased than those before operation (P < 0.05). 3. There was significant difference in the indexes among preoperative stage IIIA, IIIB and IB, and between preoperative N2 diseases and N0 group (P < 0.05). There was significant difference between the groups of radical and palliative operation and the group of thoracic exploration at postoperative 28th day (P < 0.05). There was significant difference in T subsets between the groups of blood transfusion and non-transfusion at postoperative 14th day (P < 0.05).

CONCLUSIONSThe cellular immune function of the patients with lung cancer was lower than that of the patients with lung benign tumor and normal people. The perioperative immunity of patients with lung cancer decreases after operation and increases later. TNM stage and lymph node metastasis are relative to preoperative but not postoperative immunity. There is no significant correlation between cellular immune function and pathological type of the tumor. Radical and palliative operations can both significantly increase the patients' cellular immune function. Therefore the palliative operation is better than thoracic exploration. Blood transfusion can depress the immune function of the patients, so it is better to avoid perioperative blood transfusion.

OBJECTIVETo screen potential mutation of the CRELD1 gene in congenital atrioventricular septal defect (AVSD) and explore its functional implications.

METHODSFragments encompassing the 11 coding exons of CRELD1 gene, including at least 50 bp of flanking intronic regions, were amplified with PCR and subjected to DNA sequencing. Results of sequencing were compared with predicted sequence from the GenBank database. Eukaryotic expression vector pcDNA3.1CRELD1 containing the mutational sequence was constructed. Western blotting and real-time fluorescent quantitative reverse transcription polymerase chain reaction (FQ RT-PCR) was applied to examine the expression of CRELD1, Tenascin C and Aggrecan.

RESULTSC857G was identified in a girl with an isolated partial AVSD. The mutation has resulted in a substitution of Alanine for Proline at amino acid 286 in the first cbEGF domain. Western blotting and FQ RT-PCR confirmed that the P286R missense mutation has been a gain-of-function mutation. Compared with the unloaded control, the Aggrecan mRNA expression was downregulated for both wild-type and mutant type samples (t=140.27 vs. 26.36, P < 0.01). The downregulation was more significant in mutant type (t=25.69, P=0.002). There was no significant difference of the Tenascin C expression between wild-type and the unload control (t=1.167, P> 0.05), whilst the Tenascin C expression was up-regulated in mutant type (t=6.66, P=0.022).

CONCLUSIONMutation of the CRELD1 gene may increase the risk for AVSD rather than being directly causative. The P286R mutation of CRELD1 can downregulate the expression of Aggrecan and upregulates the expression of Tenascin C protein, both of which are crucial to extracellular matrix in the formation of the atrioventricular septum. The P286R mutation of CRELD1 may be correlated to the occurrence of AVSD.

Adolescent ; Amino Acid Sequence ; Animals ; Base Sequence ; Cell Adhesion Molecules ; chemistry ; genetics ; metabolism ; Child ; Child, Preschool ; Extracellular Matrix Proteins ; chemistry ; genetics ; metabolism ; Female ; Heart Septal Defects ; genetics ; metabolism ; pathology ; Humans ; Infant ; Male ; Molecular Sequence Data ; Mutation, Missense ; Sequence Alignment