Objective To investigate the changes and clinical significance of the plasma growth differentiation factor-15 (GDF-15) in patients with chronic congestive heart failure (CHF). Methods A total of 100 patients with CHF were in?cluded in this study (CHF group), and 30 healthy persons were used as control group. CHF group was divided into heart func? tionⅡgrade (n=35),Ⅲgrade (n=32),Ⅳgrade (n=33) groups in accordance with New York Heart Association (NYHA). And CHF group was also divided into left ventricular ejection fraction (LVEF)<0.4 grade (n=52) and LVEF≥0.4 grade (n=48) groups in accordance with LVEF of patients. The plasma GDF-15 and brain natriuretic peptide (BNP) levels were detected by ELISA. The values of LVEF, left ventricular end-diastolic diameter (LVDd), left ventricular systolic diameter (LVDs) and left ventricular fractional shortening (LVFS) were detected by echocardiography. The correlation of GDF-15, NYHA classifi?cation, BNP and index of echocardiography was analyzed between groups. Results Compared with control group, the levels of BNP, GDF-15, LVDd and LVDs were significantly higher in heart failure group, and values of LVEF and LVFS were sig?nificantly lower (P<0.05). The plasma levels of BNP, GDF-15, LVDd and LVDs were in turn increased in control group, LVEF≥0.4 grade group and LVEF<0.4 grade group. The plasma levels of LVFS were in turn decreased, in control group, LVEF≥0.4 grade group and LVEF<0.4 grade group (P<0.05). There were positive correlations between the plasma levels of GDF-15 and BNP, NYHA, LVDd and LVDs (r=0.524, 0.286, 0.453 and 0.531, P<0.05). The plasma level of GDF-15 was negatively correlated with LVEF and LVFS (r=-0.592,-0.587,P<0.05). Conclusion The plasma level of GDF-15 can be used as a new marker for diagnosis, treatment and prognosis in patients with chronic congestive heart failure.

Objective: To investigate the protection roll of rosuvastatin on chronic heart failure (CHF) in rats with its effect on asymmetric dimethylarginine (ADMA) metabolic pathway.
Methods: A total of 36 male SD rats were randomly divided into 3 groups, n=12 in each group. Isoproterenol (ISO) group, the rats received ISO subcutaneous injection (5mg·kg·d) for 7 days to establish CHF model, and then received normal saline gavage administration for 7 days. Rosuvastatin (ROS) treatment group, the rats received ISO with ROS for 7 days, then continuously receiving ROS until 14 days. Normal control group, the rats received saline gavage administration for 7 days. The related serum index and haemodynamic parameters were examined, myocardial pathological changes were observed and the relevant protein expression was measured by Western blot analysis.
Results: Compared with Normal control group, ISO group had obviously increased troponin (cTn I), serum ADMA,-LVdP/dtmin, all P<0.01, and decreased left ventricular systolic pressure (LVSP), heart rate, arterial SP, mean arterial pressure, +LVdP/dtmax, all P<0.01. Compared with ISO group, ROS treatment group showed signiifcantly decreased BNP, cTn I, ADMA , -LVdP/dtmin, all P<0.01, and increased LVSP, heart rate, arterial SP, mean arterial pressure,+LVdP/dtmax, all P<0.01. Compared with Normal control group, ISO group had increased expression of protein arginine methyltransferases 1 (PRMT1), decreased expression of dimethyl- arginine dimethylaminohydrolase 2 (DDHA2), both P<0.01. Compared with ISO group, ROS treatment group showed decreased expression of PRMT1, P<0.01 and similar expression DDHA2, P>0.05.
Conclusion: Rosuvastatin has the protective roll on ISO induced CHF in rats, which might be related to decreased serum levels of cTn I, BNP and ADMA metabolic pathway regulation.

Background and purpose:The effective rate of ifrst-line chemotherapy for advanced lung cancer is 30%-40%. The purpose of this study was to evaluate the efifcacy and adverse effects of pemetrexed combined with carboplatin or cisplatin in the treatment of patients with advanced non-squamous non-small cell lung cancer (NSCLC). Methods:One hundrend and twenty-one patients with advanced non-squamous NSCLC were enrolled in this study and all of these patients had been conifrmed with pathology or cytology. Among the 121 cases, 60 cases were male and 61 were female, the median age was 59 years, adnenocarcinoma in 113 patients and large cell carcinoma in 8 patients. Combination regimen: patients received pemetrexed 500 mg/m2 on day 1 and carboplatin 300 mg/m2 or cisplatin 70 mg/m2 on day 1 by intravenous infusion, administrated every 3 weeks for 2 to 6 cycles. All patients who received 2 or more cycles could be evaluated. Disease control rate (DCR) was the primary end point; secondary end points included progression-free survival (PFS), 1-year survival rate and safety.Results:There was 1 case with complete response (CR), 44 cases achieved partial response (PR), 50 had stable disease (SD) and 26 cases had progressive disease (PD) in the overall cases. ORR and DCR were 37.2% (45/121) and 78.5% (95/121), respectively. The median PFS time was 5.2 months and 1-year survival rate was 59.0%. In pemetrexed combined with carboplatin group, the ORR and DCRwere 38.3% (23/60) and 78.3% (47/60), respectively; The median PFS was 5.1 months (95%CI: 3.8-6.4 month) and 1-year survival rate was 55.2%. The patients treated with pemetrexed plus cisplatin, the ORR and DCR were 36.1% (22/61) and 78.7% (48/61), respectively. Median PFS was 6.2 months (95%CI: 4.3-8.1 month) and 1-year survival rate was 62.5%. There were no statistical differences between carboplatin/pemetrexed and cisplatin/pemetrexed for both ORR, DCR, PFS and 1-year survival rate (P>0.05). The major adverse effects were leukopenia, neutropenia, fatigue and gastrointestinal reaction.Conclusion:Pemetrexed plus platinum chemotherapy could be considered as the ifrst-line treatment option for advanced non-squamous NSCLC patients. Pemetrexed combined with carboplatin/ cisplatin regimen has efifcacy with mild toxicity and better tolerability.

Background and Purpose:Lung cancer is the most malignant tumour in the world.Its incidence is growing and NSCLC is predominent(80%) in lung cancer.Most patients with lung cancer were diagnosed in late stages.The tumour could be shrunk by neoadjuvant chemotherapy when the case with stage Ⅲ NSCLC was considered not possible for radical operated neoadjuvant chemotherapy may lead to the following,operation could be improved,micrometastasis could be annihilated and survival could be extended.Objective of this paper was to analyse the prognostic factors for survival in patients treated by surgery and chemotherapy for NSCLC.Methods:98 cases of neoadjuvant chemotherapy combined with surgery for NSCLC,stageⅠ~Ⅲ,were collected retrospectively in our hospital from 1995 to 1997.35 cases were stageⅠ.21 cases were stage Ⅱ.42 cases were stage Ⅲ.83 cases had 1 cycle of chemotherapy pre-operatively.15 cases had 2 cycles chemotherapy pre-operatively.Regimes of chemotherapy were MVP,MOP and MAP et al.Response rate(RR) of chemotherapy was:45 cases had partial response(PR) and 53 cases were stable disease(SD).Operative mode was lobectomy and pneumectomy with lymph nodes dissection.Pathologic type was squamous,adeno,adeno-squamous and others.All the patients were treated by chemotherapy for two or three cycles after surgery except for the patients in stageⅠin 1996~1997.After being followed-up for more than 5 years,data were examined using life table,KaplanMeier method,Log Rank statistic and Cox-mantel test.The possible factors affecting survival were tested with univariate and multivariate analysis.Results:The median followed-up time of 98 cases for NSCLC was 41.2 months.36 cases were alive.62 cases were dead.The 1-,3-,5-year survival rate of 98 cases for NSCLC was 88.78%、49.63% and 18.46%.The 5-year survival rates of stageⅠ、ⅡandⅢ were 33.23%、20.26% and 5.52% respectively(P=0.0002).The 5-year survival rates of N_(0)、N_(1)、N_(2) were 35.49%、19.08% and 4.90% respectively(P=0.0004).In the 98 cases of NSCLC,better prognosis was correlated with earlier stage.The prognosis was better if the period from last chemotherapy before operation to operation was no more than 1 month. The prognosis of lobectomy,lung hila activity,thorax lymph nodes negativity and squamous cancer was better.The prognosis was poorer if the tumor had invaded big vessels,viscera,chest wall,pericardium and quantity bleeding during≥400ml.The prognosis was better if the tumor was fibrotic.The prognosis of 2 cycles of chemotherapy pre-operatively might be better than 1 cycle.The prognosis of tumor necrosis was poorer and the prognosis of chemotherapy post-operatively was better.Conclusions:The main prognostic factors affecting survival in patients treated by surgery and chemotherapy for NSCLC was stage,the period from last chemotherapy before operation to operation,operation mode,lung hila activity,thorax lymph nodes,site of tumor invasion,bleeding quantity,pathologic type,tumor fibrosis and necrotis,cycles chemotherapy pro-operation and chemotherapy post-operation.

OBJECTIVETo analyze the clinical phenotype of a Chinese pedigree affected with hereditary dentinogenesis imperfecta and mutation of dentin sialophosphoprotein (DSPP) gene.

METHODSAffected members underwent intraoral photography, dental film and panoramic radiography. Genomic DNA was extracted from peripheral venous blood samples. Coding regions of the DSPP gene were subjected to PCR amplification and Sanger sequencing. Functional effect of the mutation was predicted with SIFT and PolyPhen-2. The tertiary structure of wild type and mutant proteins were predicted by Swiss-Port.

RESULTSA heterozygous c.50C to T (p.P17L) mutation was identified in exon 2 of the DSPP gene in the proband and her father. The same mutation was not found among 200 unrelated healthy controls. The Pro-17 residues and its surrounding positions in DSPP are highly conserved across various species. The mutation was predicted to be damaging to the structure of DSPP protein.

CONCLUSIONThe c.50C to T (p.P17L) mutation of the DSPP gene probably underlies the disease in this pedigree. Above finding has expanded the spectrum of DSPP gene mutations and provided a basis for genetic counseling and prenatal diagnosis for this family.

Tooth development is a complex process that involves precise and time-dependent orchestration of multiple genetic, molecular, and cellular interactions. Ameloblastin (AMBN, also named "amelin" or "sheathlin") is the second most abundant enamel matrix protein known to have a key role in amelogenesis. Amelogenesis imperfecta (AI [MIM: 104500]) refers to a genetically and phenotypically heterogeneous group of conditions characterized by inherited developmental enamel defects. The hereditary dentin disorders comprise a variety of autosomal-dominant genetic symptoms characterized by abnormal dentin structure affecting either the primary or both the primary and secondary teeth. The vital role of Ambn in amelogenesis has been confirmed experimentally using mouse models. Only two cases have been reported of mutations of AMBN associated with non-syndromic human AI. However, no AMBN missense mutations have been reported to be associated with both human AI and dentin disorders. We recruited one kindred with autosomal-dominant amelogenesis imperfecta (ADAI) and dentinogenesis imperfecta/dysplasia characterized by generalized severe enamel and dentin defects. Whole exome sequencing of the proband identified a novel heterozygous C-T point mutation at nucleotide position 1069 of the AMBN gene, causing a Pro to Ser mutation at the conserved amino acid position 357 of the protein. Exfoliated third molar teeth from the affected family members were found to have enamel and dentin of lower mineral density than control teeth, with thinner and easily fractured enamel, short and thick roots, and pulp obliteration. This study demonstrates, for the first time, that an AMBN missense mutation causes non-syndromic human AI and dentin disorders.
Adult ; Amelogenesis Imperfecta ; genetics ; Cells, Cultured ; China ; Codon ; Dentin ; abnormalities ; ultrastructure ; Female ; Humans ; Male ; Microsatellite Repeats ; Microscopy, Electron, Scanning ; Middle Aged ; Mutation, Missense ; Pedigree ; RNA ; analysis ; Transfection ; Whole Exome Sequencing