OBJECTIVE: Mutations in LIM domain binding 3 (LDB3) gene cause idiopathic dilated cardiomyopathy (IDCM), a structural heart disease with a complicated genetic background. However, the association of polymorphisms in the LDB3 gene with susceptibility to IDCM in Chinese populations remains unexplored as dose the impact on clinical presentation. METHODS: We sequenced all exons and the adjacent part of introns of the LDB3 gene in 159 Chinese Han IDCM patients and 247 healthy controls. Then we detected the distribution of polymorphisms in the LDB3 gene in all participants and assessed their associations with risk of IDCM. Additionally, we conducted a stratified genotype-phenotype correlation analysis. RESULTS: The A allele of rs4468255 was significantly associated with IDCM (P<0.01). The rs4468255, rs11812601, rs56165849, and rs3740346 were also associated with diastolic blood pressure (DBP) and left ventricular ejection fraction (LVEF) (P<0.05). Notably, a higher frequency of rs4468255 polymorphism was observed in implantable cardioverter defibrillator (ICD) recipients under a recessive model (P<0.01), whereas the significant association disappeared after adjusting for potential confounders. However, in the dominant model, notable correlations could only be observed after adjusting for multi parameters. CONCLUSIONS The rs4468255 was significantly correlated with IDCM of Chinese Han population. A allele of rs4468255 is higher in IDCM patients with ICD implantation, suggesting the influence of genetic background in the generation of this response. In addition, rs11812601, rs56165849, and rs3740346 in LDB3 show association with brain natriuretic peptide, DBP, and LVEF levels in patients with IDCM but did not show any association with IDCM susceptibility.
Adaptor Proteins, Signal Transducing/genetics* ; Adult ; Aged ; Alleles ; Asian People ; Cardiomyopathy, Dilated/surgery* ; China/epidemiology* ; Defibrillators, Implantable ; Exons ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; LIM Domain Proteins/genetics* ; Linkage Disequilibrium ; Male ; Middle Aged ; Mutation ; Polymorphism, Genetic ; Sequence Analysis, DNA

Objective To explore the genetic variation in children patients with esophageal atresia (EA ) to provide a prophase basis for further studying EA pathogenesis .Methods Ten children cases of EA were collected from the neonatal surgery department of our hospital .The high-throughput whole-exon sequencing was used to study the genetic variations ,and their clinical significance was analyzed by the bioinformatics methods .Results In the high quality sequencing data ,the effective clean reads accounted for 85 .36% ,in which 97% of the clean reads could participate in the comparison with the reference genes .The comparison analysis obtained 520541 single nucleotide polymorphism sites ,in which single nucleotide variation(SNV) occurred at 149622 sites ,including synonymous mutation ,nonsynonymous mutation ,stop codon gain ,stop codon loss ,frameshift insertion ,nonframeshift insertion ,unknown mutation ;meanwhile ,598 copy number variation genes were detected .The functional cluster analysis revealed that the mutant genes were closely related to cell biology .Conclusion The SNV occurrence may influence the expression and function of body various proteins and may play an important role in EA pathogenesis .

Objective To investigate the relationship of stress hyperglycemia,cystatin C and estimated glomerular filtration rate (eGFR) with short-term prognosis in elderly patients with acute myocardial infarction.Methods 242 consecutive patients with acute myocardial infarction were divided into two groups according to age:the elderly group (n=182),and the non elderly group (n=60).The clinical data including cystatin C (Cys C),eGFR and stress hyperglycemia levels were collected.The major adverse cardiovascular events (MACE) were observed during hospitalization and 30 days after discharge.Results The incidences of stress hyperglycemia,the levels of creatinine,Cys C and brain natriuretic peptide (BNP),as well as the total MACE were higher and eGFR was lower in elderly group than in non-elderly group (all P＜0.05).Cys C level was positively correlated with age,body mass index and levels of creatinine and BNP (all P＜0.05),and negatively correlated with fasting glucose and eGFR in elderly group (both P＜0.05).The eGFR was positively correlated with body mass index (P＜0.05),and negatively correlated with age,creatinine and BNP levels in elderly group (all P＜0.05).Logistic regression analysis indicated that stress hyperglycemia [OR=1.871,95％CI:1.071-3.269,P=0.03],Cys C [OR=7.093,95％CI:2.261-22.249,P=0.00] were the independent risk factors for MACE.Conclusions Cys C level and eGFR can predict the early renal dysfunction and its prognosis in elderly patients with acute myocardial infarction.The incidence of stress hyperglycemia is higher in the elderly,and stress hyperglycemia and Cys C level are the independent risk factors for MACE.

Objective: To explore the protective effect and its molecular mechanism of apoptosis signal-regulating kinase 1 (ASK1) inhibitor (GS-459679) on acetaminophen-induced liver injury in mice. Methods: The model of liver injury was established by administration of acetaminophen (APAP) (300 mg/kg, i.p.) on C57BL/6 mice. Forty-eight male C57BL/6 mice were randomly divided into four groups, consisting of control group, GS group (GS-459679, 30 mg/kg, i.p.), APAP-induced group, and GS combined with APAP-induced group. For GS combined with APAP-induced group, mice were treated with GS 30 min prior to administration of APAP. After mice were euthanized at 6 h or 12 h, respectively, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed, and mRNA levels of TNF-α, IL-6 and IL-1β were tested. The activity of glutathione (GSH), oxidized GSH (GSSG) and malondialdehyde were quantified. In addition, ASK1, P-ASK1, JNK and P-JNK protein levels were tested in all groups. Results: The ASK1 and P-ASK1 levels were up-regulated in APAP-induced group. Compared to the control group, serum levels of ALT and AST, and mRNA levels of TNF-α, IL-6 and IL-1β were increased in APAP-induced group. Meanwhile, the levels of MAD and GSSG, and the ratio of GSSG/GSH were higher and the JNK was activatedin APAP-induced group compared with that in control group. However, compared to APAP-induced group, GS combined with APAP-induced group displayed a decrease of protein expression levels of ASK1, P-ASK1 and P-JNK, a reduction of serum levels of ALT and AST, a decrease in TNF-α, IL-6 and IL-1β mRNA levels, and a low ration of GSSG/GSH. Conclusions: GS-459679 treatment effectively down-regulates ASK1 and P-ASK1 expression. Addition of GS-459679 decreases the generation of liver metabolites and inflammatory factors, reduces oxidative stress reaction, inhibits JNK activation, and then protects the responsiveness to APAP-induced liver injury.

OBJECTIVE To explore the clinical efficacy of using Chaizhi Pinggan decoction to treat functional dyspepsia of liver-stomach disharmony type and its mechanism.METHODS 1 10 patients with functional dyspepsia due to liver-stomach disharmony were selected from March,201 5 to March,201 6 in our hospital and randomly divided into the observation group and the control group,with 55 cases in each group.The control group was given domperidone tablets while the observation group were given Chaizhi Pinggan Decoction.After 4 weeks treatment,changes in clinical symptoms and signs,serum seroto-nin(5 HT) and somatostatin(SS) content in the two groups were detected and compared.The recurrence incidence of the two groups during the three-month follow up were observed.RESULTS Such symptoms as abdominal fullness and distention, hypochondriac pain,prone to sign,poor appetite,nausea,belching and vomiting all decreased significantly(P <0.05~0.01), but the observation group reduced more significantly compared with the control group(P <0.05~0.01).TCM syndrome total scores of both groups decreased significantly after treatment(P <0.01),but the observation group reduced more significantly (P <0.01).The total efficiency of epigastric pain syndrome and postprandial distress syndrome in the observation group were 92.8% and 92.6%,which were much higher than those in the control group72.4% and 69.2%(P <0.05).After treatment both serum 5 HT and SS in the two groups went down significantly(P <0.01),with more decrease in the observation group(P<0.05).During the three-month follow ups,the recurrence rate of the observation group was 3.6%,lower than 12.7% of the control group(P <0.05).CONCLUSION Chaizhi Pinggan Decoction can significantly improve clinical symptoms of pa-tients with functional dyspepsia due to liver and stomach disharmony,whose mechanism might be related to the increase of 5 HT and decrease of SS.

The purpose of this study is to investigate the activity and mechanism of a new anti-tumor agent T03. MTT and colony formation assay were performed to determine anti-proliferation activity of T03 in vitro. Antitumor activity was observed by Renca xenograft model in vivo. The effect of T03 on cell cycle and apoptosis were measured by FCM analysis. Western blotting was performed to investigate the expression level of proteins in HepG2 cell lines treated with T03. T03 had anti-tumor activity by inhibiting tumor cell growth and colony formation in vitro, especially on hepatocellular carcinoma cells (HCC). At the concentration of 10 micromol x L(-1), T03 induced cell apoptosis and cell cycle arrest in HCC. Moreover, it proved that T03 reduced the tumor weight with the rate of 42.30% without any obviously side effect in Renca xenograft model. At the concentration of 2.0 micromol x L(-1), T03 was able to reduce the level of p-c-Raf (Ser259), and thus blocked Raf/MEK/ERK and AKT signaling in HepG2 cell lines. The result suggested that T03 has the potential to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo, particularly active against HCC, indicating T03 and its analogues may serve as a new anti-cancer drug against hepatocellular carcinoma.
Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; pathology ; Cell Cycle Checkpoints ; drug effects ; Cell Proliferation ; drug effects ; Hep G2 Cells ; drug effects ; Humans ; Liver Neoplasms ; pathology ; Signal Transduction ; drug effects ; Xenograft Model Antitumor Assays

Objective To observe the effect of different levels of iodine nutrition on rat maternal thyroid function during pregnancy.Methods A total of 225 Wistar rats one month after weaning were involved in the study(female 165,male 60,body mass 80 to 100 g).Female rats were randomly divided into six groups by body mass:control group(NI group),iodine deficiency 1 and 2 groups(LI1,LI2 groups),iodine excess 1 and 2 groups (HI1,HI2 groups),and the control of not pregnant group(NNI group).There were 30 rats in 1-5 groups and 15 rats in group 6.LI1,LI2 groups:low iodine diet + deionized water of no iodine or iodine-containing 5 μg/L; HI1,HI2 groups:normal diet + deionized water of iodine 3000,10 000 μg/L; NI,NNI groups:normal diet + deionized water of iodine-containing 50 μg/L.After 12 weeks,the females(except group 6) mated the male by 2 ∶ 1,and then each pregnant female rat was fed in a single cage.The female mice were sacrificed in the first(5 ± 2)d,the second (12 ± 2)d and the third trimesters of pregnancy (17 ± 2)d,respectively,and there blood samples and thyroid were obtained.Serum total thyroxine(TT4),free thyroxine(FT4),total triiodothyronine (TT3),free triiodothyronine (FT3) and thyroid stimulating hormone(TSH) were determined by radioimmunoassay and serum thyroglobulin(TG) and thyroid-binding globulin (TBG) were determined by enzyme-linked immunosorbent assay.Results ①Thyroid absolute quality and relative quality was compared among groups,and the differences were statistically significant (F =16.55,24.25,F ＜ 0.01 or ＜ 0.05).②At the first,the second and the third trimesters of pregnancy,the differences of maternal serum TT4 and FT4 between groups were statistically significant(F =5.02,13.41,17.39,41.89,23.72,48.64,P ＜ 0.01 or ＜ 0.05).Female rats in NI,HI1 and HI2 groups in different pregnant periods among inner groups were compared,and the differences of serum TT4 and FT4 were statistically significant(F=3.27,6.98,8.22,8.65,29.68,7.90,P ＜ 0.01 or ＜ 0.05).③ In the first and the third trimesters of pregnancy,maternal serum TT3 was compared among groups,and the differences were statistically significant(F=3.59,8.22,P ＜ 0.05 or ＜ 0.01) ; in the second and the third trimesters of pregnancy,maternal serum FT3 was compared among groups,and the difference was statistically significant(F =3.86,4.26,P ＜ 0.05 or ＜ 0.01).Female rats in NI,LI1 and HI1 groups in different pregnant periods among inner groups were compared,and the differences of maternal serum TT3 were statistically significant(F =8.77,7.11,6.28,P ＜ 0.01 or ＜ 0.05).④At the first,the second and the third trimesters of pregnancy,the differences of maternal serum TG and TBG were compared in groups,and the differences were statistically significant(F =5.47,3.62,9.35,4.15,13.16,22.78,P ＜ 0.01 or ＜ 0.05).The differences of maternal serum TG of HI1 group and of serum TBG of NI group in different pregnant periods among inner groups were statistically significant (F =3.18,7.94,P ＜ 0.05).⑤At the first,the second and the third trimesters of pregnancy,the differences of maternal serum TSH in groups were statistically significant(F =4.83,7.08,6.52,P ＜ 0.01); the differences of maternal serum TSH of all the 5 groups in different pregnant periods among inner groups were statistically significant (F =3.26,8.89,11.45,4.04,3.78,P ＜ 0.05).Conclusions Different levels of iodine nutrition can cause changes in thyroid function in rats maternal thyroid function during pregnancy; serum TT4,FT4 level decreases when iodine deficiency,and increase with iodine excess.Serum TT3,FT3 level of does not changed significantly due to compensatory regulation of the body.

ObjectiveTo study the mRNA expression of rat Insulin-like growth factors- Ⅰ (IGF- Ⅰ ) and Transforming growth factor-β1 (TGF-β1) in thyroid and placenta with different iodine intakes during pregnancy.MethodsOne hundred and fifty female Wistar rats,weighting 80 - 100 g,were randomly divided into five groups according to body weight,30 rats in each group.Each group was given deionized water containing different concentrations of iodine,50 μg/L(control group,NI),0 μg/L(iodine deficiency 1 group,LI1 ),5 μg/L(iodine deficiency 2 group,LI2),3000 μg/L(iodine excess 1 group,HI1 ),and 10 000 μg/L(iodine excess 2 group,HI2),respectively.After feeding for 12 weeks,the female rats were mated with male rats.The female rats were sacrificed at first(6,7 days),trimester( 12,13 days),and third trimesters( 19,20 days),respectively,then their thyroid and placenta were collected.The mRNA expressions of IGF- Ⅰ and TGF-1 in thyroid and placenta were detected by real-time quantitative PCR.Results①The actual thyroid weights of LI1 and LI2 groups[ (12.17 ± 5.41 ) × 10-2 g,(3.54 ± 1.21) × 10-2 g] were significantly higher than that of NI group[ (2.05 ± 0.50) × 10-2 g,all P ＜ 0.05] ;actual weights of HI1 and HI 2 groups[ (1.64 ± 0.27) × 10-2 g,(1.66 ± 0.29) × 10-2 g] were compared with that of NI group,the difference was not statistically significant(all P ＞ 0.05).②The mRNA expression of IGF- Ⅰ: at the first trimester,LI1 and LI2 groups(l.98 ± 0.35,1.47 ± 0.22) were all higher than that of NI group(1.01 ± 0.18,all P＜ 0.01 ),HI1 and HI2 groups(0.68 ± 0.16,0.75 ± 0.09) were lower than that of NI group(all P ＜ 0.01 );at the second trimester,HI2 group( 1.14 ± 0.17) was lower than that of NI group( 1.58 ± 0.33,P ＜ 0.01 ) ; at the third trimester,LI2 and HI2 groups(1.47 ± 0.20,1.45 ± 0.35) were lower than that of NI group(2.20 ± 0.37,all P＜0.01).The mRNA expression of IGF- I level in NI group at the first,second,and third trimesters(1.01 ±0.18,1.58 ±0.33,2.20 ± 0.37) was up regulated gradually,pairwise comparisons were statistically significant(all P ＜ 0,01 ).③The mRNA expression of TGF-β1: at the first trimester,LI1 group (1.37 ± 0.13) was higher than NI group (1.05 ±0.18,P ＜ 0.01 ),HI1 and HI2 groups(0.50 ± 0.09,0.44 ± 0.11) were lower than NI group(all P＜ 0.01); at the second trimester,LI1 and HI2 groups(1.39 ± 0.28,1.17 ± 0.12) were higher than NI group(0.63 ± 0.22,all P ＜0.01 ) ; at the third trimester,LI1 and LI2 groups ( 1.57 ± 0.30,1.23 ± 0.20) were higher than NI group ( 0.68 ± 0.17,all P＜ 0.01).TGF-β1 mRNA expressions of NI group at the second (0.63 ± 0.22) and third trimesters(0.68 ± 0.17) were lower than that of the first trimester (1.05 ± 0.18,all P ＜ 0.01).④ Rats' IGF-Ⅰ mRNA expression in placental: at the second trimester HI1 group,HI2 group( 1.48 ± 0.16,1.45 ± 0.25) were all higher than the NI group ( 1.00 ± 0.10,all P ＜ 0.01 ) ; at third trimester,HI1 group ( 1.75 ± 0.15 ) were higher than the NI group ( 1.54 ± 0.29,P＜ 0.05),HI2 group(l.94 ± 0.31) were higher than the NI group(P ＜ 0.01 ).IGF- Ⅰ mRNA expression in placental of NI group at the third trimester was higher than the second trimester(P＜ 0.01).⑤ Rats' TGF-β1 mRNA expression in the placenta: at the second trimester and the third trimester of pregnancy there were no significant difference between the five groups(all P ＞ 0.05) ; NI group at the third trimester(0.83 ± 0.16) was lower than the second trimester(0.98 ± 0.20,P ＜ 0.05).Conclusions During pregnancy,IGF- I mRNA expression increases in thyroid under the conditions of iodine deficiency,and this effect is particularly significant in the first trimester; at the same time,TGF-β1 mRNA expression is increased,and this inhibition becomes clear with the deepening of iodine deficiency.Under the condition of iodine excess,the functions of IGF- Ⅰ and TGF-β1 in thyroid above-mentioned were relatively weak.With the development of gestational period,promoting tissues growth and differentiation effect of placenta's IGF- Ⅰ was more significant gradually,but,inhibited effect of TGF-β1 was weaken.

Objective To study the effect of different levels of iodine nutrition on secretion of placental hormone in pregnant rats.Methods Two hundred and twenty five Wistar rats (165 female,60 male),weighing about 80 - 100 g were used in the study.Female rats were randomly divided into five groups according to their body weights:low iodine group Ⅰ(LⅠ),low iodine group Ⅱ (LⅡ),adequate iodine(control) group(Al),high iodine group Ⅰ ( HⅠ ),and high iodine group Ⅱ (H Ⅱ ),and 33 rats in each group.Animals in the low iodine groups were fed low-iodine diet,the iodine content was 13.46 μg/kg,in addition,these rats drank deionized water which containing potassium iodated,the dose was 0 and 5 μg/L,respectively.The rats of adequate and the two high iodine groups were fed normal diet,the iodine content was 22.00 μg/kg,they also drank deionized water,containing potassium iodated 50,3000,and 10000 μg/L,respectively.The rats mated after 3 months of feeding,and were respectively sacrificed at early pregnancy(5 ± 2)d,second trimester( 12 ± 2)d,and third trimester of pregnancy(17 ± 2)d,and then their serum was taken.Serum human chorionic gonadotropin(HCG),human chorionic thyrotropin(HCT),and progesterone were measured by enzyme-linked immunosorbent assay (ELISA).Results In the third trimester,the serum levels of rat HCG were significantly different between groups(F =4.16,P ＜ 0.05).The means of rats serum HCG of the two low iodine groups [ (16.08 ± 4.45),(17.43 ± 2.70)U/L] were significantly higher compared with that of AI group[ (13.68 ± 3.52)U/L] in the third trimester(all P ＜ 0.01 ).In the second and third trimester,the levels of rats serum HCT were significantly different between groups(F =3.59,3.40,all P ＜ 0.05).The means of rats serum HCT of HI group [(70.11 ± 10.97)μU/L] in the second trimester and HII group[(74.93 ± 13.22)μU/L] in the third trimester were higher than those of AI group[ (57.14 ± 12.56),(58.17 ± 8.54)μU/L] significantly(all P ＜ 0.01 ).There were statistical differences of the means of serum progesterone among trimester of pregnancy(F =4.06,4.43,all P ＜ 0.05).The level of serum progesterone of the third trimester[ ( 1462.80 ± 286.48 )pmoL/L] compared to those of the first[ (1929.93 ± 158.37) pmol/L] and the second trimester[ (1856.44 ± 542.08)pmol/L] was decreased significantly(all P ＜ 0.05) in LI group.In the control group,the level of serum progesterone of the second trimester [ (2046.45 ± 475.67)pmol/L ] was significantly higher than the first trimester[ (1714.39 ± 461.71 )pmol/L,P ＜ 0.05 ].Conclusions During pregnancy,placenta could promote HCG secretion under iodine-deficient conditions.In addition,the placenta increases the secretion of HCT under conditions of excess iodine.In the condition of severe iodine deficiency,the secretion of serum progesterone decreases,and further decreases with prolongation of pregnancy,but it is opposite to the change of HCG during pregnancy.This phenomenon could lead to harmful pregnant outcomes easily.

OBJECTIVETo report the mid- to long-term outcome of artery bypass in chronic ischemia of lower extremities.

METHODSThe clinical data of 212 patients treated with bypass operation from January 2002 to April 2007 were retrospectively reviewed. Femoropopliteal artery bypass to above-knee popliteal (FP-ak) was carried out in 111 cases, femoropopliteal artery bypass to below-knee popliteal (FP-bk) in 59 cases, aortoiliac bypass in 25 cases and femorofemoral bypass in 17 cases.

RESULTSOne hundred and eighty-six patients (87.7%) were followed up for 6 to 68 months (median, 18 months). One-year primary patency rate of FP-ak and FP-bk was 69.7% and 53.5%, respectively. After graft revision, 1-year secondary patency rate of FP-ak and FP-bk were 81.6% and 60.5%, respectively. The 3-year patency with FP-ak (56.3%) was significantly higher than that in FP-bk (23.8%) (P < 0.05). Fifty-two cases were reoperated on during the follow-up period. Crural or femoral amputation could not avoid in 23 cases (limb salvage rate 89.2%). Ten cases died in 1 to 30 days after the operation, 20 cases died later during followup, and most of them died of cardio-cerebrovascular diseases. Artificial vessel infection occurred in 6 cases.

CONCLUSIONSThe selection of surgical treatment for chronic ischemia of lower extremities should based on the ischemic state of the limb. The mid- to long-term patency rate of FP-ak is higher than that of FP-bk.

Adult ; Aged ; Aged, 80 and over ; Arterial Occlusive Diseases ; surgery ; Female ; Follow-Up Studies ; Humans ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Vascular Surgical Procedures ; methods