OBJECTIVE: To investigate the gene mutations types and the clinical characteristics in 3 patients with hereditary coagulation factor Ⅶ deficiency. METHODS: The phenotype diagnosis was validated by detecting the coagulation parameters including prothrombin time (PT)，activated partial thromboplastin time (APTT), fibrinogen (FIB), FⅦ activity (FⅦ: C) and specific antigens (FⅦ: Ag) of proband and its family members. All exons, exon-intron boundaries, 5＇ untranslated regions and 3＇ untranslated regions of F7 gene were amplified with PCR. Potential mutations were detected by direct sequencing of purified PCR products. Suspected mutations were confirmed by sequencing of the opposite strand. RESULTS: A total of 5 different mutations were identified in 3 patients with hereditary coagulation factor Ⅶ deficiency and family members, including 4 misssense mutations and 1 splice site mutation. Out of 3 cases of hereditary coagulation factor Ⅶ deficiency 2 had double heterozygous mutation, I had homozygous mutations. Patient 1 had p.His408Gln with p.Arg413Gln double heterozygous mutations, her sister had p.His408Gln with p.Arg413Gln double heterozygous mutations, another one had p.His408Gln mono-heterozygous mutation, their correspo FⅦ: C were 5%, 3%, 75%. Patient 2 had p.Arg364Gln with p.His408Gln double heterozygous mutations, her brother had p.Arg364Gln with IVS6-1G＞A double heterozygous mutations, their corresponding FⅦ: C were 2.0%, 2.0%. Patient 3 had p.Arg337Cys homozygous mutation, FⅦ: C was 3.0%. CONCLUSION A total of 5 different mutations were identified in 3 patients with hereditary coagulation factor Ⅶ deficiency, the p.His408Gln is a common mutation, the FⅦ: C and FⅦ: Ag have no correlation with clinical phenotypes.
Factor VII ; Factor VII Deficiency ; Female ; Heterozygote ; Homozygote ; Humans ; Male ; Mutation ; Pedigree ; Phenotype

OBJECTIVE: To study the clinical features and gene mutation spectrum of children with sideroblastic anemia (SA) and the clinical value of targeted next-generation sequencing in the molecular diagnosis of children with SA. METHODS: Clinical data were collected from 36 children with SA. Targeted next-generation sequencing was used to detect mutations in SA-related pathogenic genes and genes associated with heme synthesis and mitochondrial iron metabolism. The association between genotype and clinical phenotype was analyzed. RESULTS: Of the 36 patients, 32 had congenital sideroblastic anemia (CSA) and 4 had myelodysplastic syndrome with ring sideroblasts (MDS-RS). Mutations in CSA-related genes were detected in 19 children (19/36, 53%), among whom 9 (47%) had ALAS2 mutation, 4 (21%) had SLC25A38 mutation, and 6 (32%) had mitochondrial fragment deletion. No pathogenic gene mutation was detected in 4 children with MDS-RS. Among the 19 mutations, 89% (17/19) were known mutations and 11% (2/19) were novel mutations. The novel mutation of the ALAS2 gene c.1153A>T(p.I385F) was rated as "possibly pathogenic" and the novel mutation of the SLC25A38 gene c.175C>T(p.Q59X) was rated as "pathogenic". CONCLUSIONS ALAS2 and SLC25A38 gene mutations are commonly seen in children with CSA, but mitochondrial gene fragment deletion also accounts for a relatively high proportion. For children with hypoplastic anemia occurring in infancy, mitochondrial disease should be considered.
5-Aminolevulinate Synthetase ; Anemia, Sideroblastic ; genetics ; Child ; Genetic Diseases, X-Linked ; Humans ; Mitochondrial Membrane Transport Proteins ; Mutation ; Myelodysplastic Syndromes ; Phenotype

OBJECTIVE: To evaluate the association between Chinese medicine (CM) therapy and disease-free survival (DFS) outcomes in postoperative patients with non-small cell lung cancer (NSCLC). METHODS: This multiple-center prospective cohort study was conducted in 13 medical centers in China. Patients with stage I, II, or IIIA NSCLC who had undergone radical resection and received conventional postoperative treatment according to the National Comprehensive Cancer Network (NCCN) guidelines were recruited. The recruited patients were divided into a CM treatment group and a control group according to their wishes. Patients in the CM treatment group received continuous CM therapy for more than 6 months or until disease progression. Patients in the control group received CM therapy for less than 1 month. Follow-up was conducted over 3 years. The primary outcome was DFS, with recurrence/metastasis rates as a secondary outcome. RESULTS: Between May 2013 and August 2016, 503 patients were enrolled into the cohort; 266 were classified in the CM treatment group and 237 in the control group. Adjusting for covariates, high exposure to CM was associated with better DFS [hazard ratio (HR) = 0.417, 95% confidential interval (CI): 0.307-0.567)]. A longer duration of CM therapy (6-12 months, 12-18 months, >24 months) was associated with lower recurrence and metastasis rates (HR = 0.225, 0.119 and 0.083, respectively). In a subgroup exploratory analysis, CM therapy was also a protective factor of cancer recurrence and metastasis in both stage I-IIIA (HR=0.50, 95% CI: 0.37-0.67) and stage IIIA NSCLC postoperative patients (HR = 0.48, 95% CI: 0.33-0.71), DFS was even longer among CM treatment group patients. CONCLUSIONS Longer duration of CM therapy could be considered a protective factor of cancer recurrence and metastasis. CM treatment is associated with improving survival outcomes of postoperative NSCLC patients in China. (Registration No. ChiCTR-OOC-14005398).

Objective To explore the diagnostic value of urine neutrophil gelatinase-associated lipocalin (NGAL) in children with acute pyelonephritis. Methods A total of 104 children with urinary tract infection admitted to Tianjin Children's Hospital from December 2016 to May 2017 were selected in this study, including 61 cases with acute pyelonephritis (group APN) and 43 with lower urinary tract infection (group non-APN). The serum levels of beta 2-Microglobulin (β2-MG), cystatin C (CysC), C-reactive protein (CRP), procalcitonin (PCT) and urine levels of NGAL were compared between two groups.Receiver operating characteristic(ROC)curves were drawn to evaluate the diagnostic values of serum β2-MG,CysC,CRP,PCT and urine NGAL.Results The serum levels of CRP,PCT,β2-MG and urinary NGAL were significantly higher in APN group than those in non-APN group (P < 0.05). There was no significant difference in serum CysC level between two groups(P>0.05).The areas under the ROC curve(AUC)for serum CRP,PCT,and urinary NGAL were 0.838,0.898 and 0.963.The optimal cutoff value of serum CRP was 22.6 mg/L,the sensitivity was 75.4% and the specificity was 83.7%. The optimal cutoff value of serum PCT was 0.285 μg/L, the sensitivity was 77.0% and the specificity was 93.0%.The optimal cutoff value of urine NGAL was 473 μg/L,the sensitivity was 82.0% and the specificity was 97.7%.Conclusion Urinary NGAL has high diagnostic value for APN in children,and which is helpful for the early identification of APN.

Objective To analyze the rates of occurrence,presentations and treatment of coronary intramural hematomas(IMH)after coronary artery stent implantation.Methods Retrospective analysis was carried out in non-chronic total occlusion patients who developed coronary intramural hematomas after coronary artery stent implantation between January 1,2011 to December 31,2016.Statistical analysis was made in the fields clinical data,coronary angiography features,treatment provided,and postoperative follow-up date of the patients.Results Among the 26 IMH patients,the male gender(15/26,57.7％)and existiing hypertension(17/26,65.4％)were more common risk factors for IMH after coronary artery stent implantation.Fourteen patients developed coronary dissection.The coronary intramural hematomas presented as new non-spasm and non-thrombus coronary stenosis.The coronary intramural hematomas were found to have involved the distal segment to the stents in 16 patients.Two patients received balloon dilation,five patients had stents implantation after balloon dilation,13 patients(50.0％)were treated with direct stent implantation and the other 6 patients did not have further intervention.The follow up period after hospital discharge was(2.39±1.68)years.No adverse cardiovascular event occurred.Five patients received follow-up angiography examination.Two patients and another one patient were found to have coronary intramural hematomas fully resolved at three months and one year with coronary angiographic follow up,respectively.Two patients had IMH on angiography at 1 year follow up.Conclusions Coronary intramural hematomas after coronary artery stent implantation often involved the distal segment to the stent in hypertensive patients presenting as new non-spasm and non-thrombus coronary stenosis.Patients at low risk of acute coronary occlusion could receive conservative treatment.Patients with extentsive length of intramural hematomas should consider stent implantation for treatment.

This study was aimed to explore the effect of angiotensin converting enzyme 2 (ACE2) agonist diminazene aceturate (DIZE) on acute lung injury (ALI) induced by limb ischemia-reperfusion (LIR) in mice. Male 8-week-old wild-type and hACE2 transgenic ICR mice were randomly divided into 6 groups (6 in each group), including wild-type control (W), wild-type model (WL), wild-type model with DIZE administration (WLD), transgenic control (T), transgenic model (TL), and transgenic model with DIZE administration (TLD) groups. LIR model was established by 4 h reperfusion following 2 h ischemia of bilateral hindlimbs with rubber bands in mice. The WLD and TLD groups were pretreated with DIZE (15 mg/kg, i.p.) for 4 weeks before LIR. At the end of LIR, the mice were sacrificed and lung tissues were sampled. Indexes for evaluating lung injury include organ coefficient and wet/dry weight ratio (W/D), cell count and protein concentration of bronchoalveolar lavage fluid (BALF), as well as morphological change and pathological score were detected. Angiotensin II (Ang II) and Ang (1-7) levels in lung tissue were determined by using ELISA commercial kits. And the protein expressions of angiotensin II type 1 receptor (AT1) and Mas receptor protein in lung tissue were detected by Western blot. The results were as follows: (1) There was obvious lung injury in both the WL and TL groups. The lung injury in the TL group was lighter than that in the WL group. DIZE could attenuate the lung injury in both the two groups. (2) The WL group showed increased Ang II and decreased Ang (1-7) levels, whereas the TL group did not exhibit any changes of these two proteins. DIZE decreased the level of Ang II in both the WL and TL groups, and increased the level of Ang (1-7) in the WL group. (3) In the WL and TL groups, AT1 and Mas receptor protein expressions were up-regulated. DIZE reversed the change of AT1 protein expression, whereas further increased Mas receptor expression in both the two groups. These results suggest that DIZE may improve the renin-angiotensin system homeostasis by regulating ACE2-Ang (1-7)-Mas axis in local lung tissue and play a protective role in LIR-induced ALI in mice.

BackgroundThe pathogenesis of postural tachycardia syndrome (POTS) remains unclear. This study aimed to explore the changes and significance of sulfur dioxide (SO) in patients with POTS.

MethodsThe study included 31 children with POTS and 27 healthy children from Peking University First Hospital between December 2013 and October 2015. A detailed medical history, physical examination results, and demographic characteristics were collected. Hemodynamics was recorded and the plasma SOwas determined.

ResultsThe plasma SOwas significantly higher in POTS children compared to healthy children (64.0 ± 20.8 μmol/L vs. 27.2 ± 9.6 μmol/L, respectively, P < 0.05). The symptom scores in POTS were positively correlated with plasma SOlevels (r = 0.398, P < 0.05). In all the study participants, the maximum heart rate (HR) was positively correlated with plasma levels of SO(r = 0.679, P < 0.01). The change in systolic blood pressure from the supine to upright (ΔSBP) in POTS group was smaller than that in the control group (P < 0.05). The ΔSBP was negatively correlated with baseline plasma SOlevels in all participants (r = -0.28, P < 0.05). In the control group, ΔSBP was positively correlated with the plasma levels of SO(r = 0.487, P < 0.01). The change in HR from the supine to upright in POTS was obvious compared to that of the control group. The area under curve was 0.967 (95% confidence interval: 0.928-1.000), and the cutoff value of plasma SOlevel >38.17 μmol/L yielded a sensitivity of 90.3% and a specificity of 92.6% for predicting the diagnosis of POTS.

ConclusionsIncreased endogenous SOlevels might be involved in the pathogenesis of POTS.

OBJECTIVETo investigate the protective effect of exendin-4 against diabetic cardiomyopathy in mice and explore the underlying mechanism.

METHODSC57BL/6J mice were randomly divided into normal control group with normal diet and diabetic group with high-fat diet for 4 weeks before streptozotocin injection. The successfully established diabetic mouse models were divided into diabetic group with exendin-4 treatment and diabetic control group for daily treatment with intraperitoneal injection of 1 nmol/kg exendin-4 and saline of equivalent volume for 8 weeks, respectively. The physiological parameters such as blood glucose and body weight were recorded. RT-PCR was used to examine the transcription levels of genes related with myocardial hypertrophy and fibrosis and the genes related with mitochondrial functions including PGC1α, NRF and CytoC. The expressions of oxidative stress markers and Sirt1/PGC1 proteins were measured using Western blotting. and HE staining was used to observe the myocardial structural changes in the mice.

RESULTSCompared with the normal control mice, the mice in diabetic control group showed significantly increased blood glucose and blood lipid levels (P<0.001), which were obviously improved by Exendin-4 treatment. The expressions of ANP, BNP, TGFβ1, CytoC1 and NOX1 were significantly increased (P<0.05) while Sirt1, PGC1α, NRF and SOD1 expression were markedly decreased in the myocardial tissue of the diabetic mice (P<0.05). Exendin-4 treatment resulted in obviously reduced expressions of ANP, BNP, TGFβ1, CytoC1 and NOX1 (P<0.05) and increased expressions of Sirt1, PGC1α, NRF and SOD1 (P<0.05) in the diabetic mice.

CONCLUSIONSExendin-4 protects against myocardial injury in diabetic mice by improving mitochondrial function and inhibiting oxidative stress through the Sirt1/PGC1α signaling pathway.

OBJECTIVE: To evaluate the level of blood pressure control in patients with coronary heart disease (CHD) of China in order to provide guidance for the prevention and treatment of CHD. METHODS: The patients with CHD were retrospectively collected from 2011~2014 in PLA General Hospital and Hainan Branch Hospital. Then analyzed the difference of blood pressure compliance rate between different surgical methods percutaneous coronary intervention (PCI), coronary artery bypass grafting(CABG), secondary preventive drugs(aspirin, clopidogrel, nitrates, trimetazidine, nicorandil, hypotensor, hypoglycemic, lipid-lowering drugs) and lifestyle(smoking, drinking, exercise). RESULTS: ①Effects of surgical methods on blood pressure:Male's systolic blood pressure (SBP) and diastolic blood pressure(DBP) in the CABG group were lower in the PCI group and control group, and female's DBP in the CABG group were lower in the PCI group. ②Usage rate of secondary prevention drugs:usage rate of trimetazidine, calcium antagonist, β-blockers, angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor antagonist (ARB) in hypertension group were higher than in normal blood pressure group. ③ Lifestyle condition:compliance rate of blood pressure in the smoking group was lower than that in the non smoking group. And there was no significant difference in blood pressure compliance rate among whether drinking and doing exercise or not. CONCLUSIONS Blood pressure control in patients with CHD was still not satisfied. Compared with PCI, CABG may be more beneficial in the control of blood pressure in patients with CHD. Smoking cessation and improving the usage rate of secondary preventive drugs are still the main means of blood pressure control.
Blood Pressure ; China ; Coronary Artery Bypass ; Coronary Disease ; drug therapy ; physiopathology ; surgery ; Female ; Humans ; Life Style ; Male ; Percutaneous Coronary Intervention ; Retrospective Studies ; Treatment Outcome