Diffusion tensor imaging is a non-invasive MRI technique which can identify changes of cerebral microstructure that CT and MRI is difficult to find, especially in the change of nerve fibers direction, which can be used for the researches of evaluation, recovery mechanism and prognosis of neurology. It has been applied in rehabilitation of motor, language and recognition of post-stroke patients.

Objective: To explore the impact of atrial fibrillation (AF) on clinical outcomes in patients with cardiac resynchronization therapy (CRT). Methods: A total of 258 arrhythmia patients who received CRT in our hospital from 2010-01 to 2014-12 were retrospectively enrolled. According to AF occurrence, the patients were divided into 2 groups: AF group,n=42 and Non-AF group,n=216. The end point events were deifned by heart failure (HF) re-admission and all-cause death (including heart transplantation). Survival curve was drawn by Kaplan-Meier method, clinical prognosis was comparedbetween 2 groups with log-rank test and the impact of AF on end point prediction was analyzed by uni- and multivariate Cox proportional-hazards regression models. Results: There were 16.3% (42/258) patients combining AF. The following indexes were statistically different between AF group and Non-AF group: patients' age, the ratios of male gender and left bundle branch block (LBBB), eGFR, blood levels of creatinine, uric acid, big endothelin-1, left atrial diameter and application of amiodarone. With the median of 22 months follow-up study, there were 33/258 (12.8%) patients died, 5 (1.9%) received heart transplantation and 72 (27.9%) with HF re-admission. Survival analysisindicated that HF re-admission rate in AF group was higher than Non-AF group (χ2=6.651,P=0.010), all cause mortality was similar between 2 groups (χ2=0.528,P=0.468). Univariate Cox proportional-hazards regression analysis showed that AF, LBBB, higher blood levels of creatinine, big endothelin-1 and large left atrium were the suspiciousrisk factors for HF re-admission; increased blood levels of creatinine, big endothelin-1 and large left atrium were thesuspiciousrisk factors for all cause death. Multivariate Cox proportional-hazards regression analysis presented that AF was not the independent risk factor for HF re-admission and all-cause death, while largeleft atrium was the independent risk factor for HF re-admission (HR=1.041, 95% CI 1.007-1.075,P=0.018); large left atrium and increased serum creatinine were the independent risk factors for all cause death (HR=1.045, 95% CI 1.001-1.091,P=0.048) and (HR=1.008, 95% CI 1.001-1.015,P=0.035) respectively. Conclusion: AF was associated with the higher rate of HF re-admission in CRT patients; while no clear evidencesupported that AF was the independent risk factor for HF re-admission and all cause death in CRT patients.

In order to profoundly understand the clinical and laboratorial characteristics and inducing factors of hemophagocytic lymphohistiocytosis syndrome (HLH), 28 HLH patients received from 2004 to 2009 years in our hospital were analyzed retrospectively. The results indicated that all of the patients had a history with prolonged fever (more than 1 week), pancytopenia, hepatosplenomegaly, elevated ferritin level, hypofibrinogen, and hemophagocytosis in bone marrow. HLH was the first characteristic sign of malignant lymphoma in 9 patients; 1 patient had a clinical manifestation similar to fulminant hepatic failure; severe psycho-abnormality occurred in 1 HLH patient and pronounced hemophagocytosis were detected in his cerebrospinal fluid; 1 patient was eventually diagnosed as having HLH by the findings in a lymph node biopsy showing obvious hemophagocytosis. Additionally, the analysis of underlying factors in 28 patients with HLH indicated 11 patients with EB virus-associated HLH, 11 with lymphoma-associated HLH, 2 with Leishmania-associated HLH, and 3 with autoimmune disease-associated HLH. It is concluded that HLH disease is characterised with high heterogenicity in both clinical features and inducing factors; in addition, the patients from a pasturing area should be paid attention to parasite infection such as leishmania.
Adolescent ; Adult ; Aged ; Autoimmune Diseases ; complications ; Child ; Child, Preschool ; Female ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Leishmania ; isolation & purification ; Lymphohistiocytosis, Hemophagocytic ; complications ; diagnosis ; parasitology ; virology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

OBJECTIVETo investigate the CYP17A1 gene mutations in a Chinese 46,XX patient with partial combined 17 alpha-hydroxylase/17,20-lyase deficiency.

METHODSClinical data were retrospectively analyzed. The genomic DNA of the patient and her parents was isolated from whole blood. Seven pairs of primers were used to amplify eight exons and exon-intron boundaries of the CYP17A1 gene. The amplified PCR products were purified by agarose gel and then directly sequenced. In order to confirm the DNA sequences of different alleles, some fragments were inserted into pMD 18-T vector and then subclone sequenced. Sequencing results were compared to the established human CYP17A1 sequence.

RESULTSThe patient was new compound heterozygous of 5994-5995 delAT/7541 C>T. The mutation 5994-5995 del AT, causing amino acid I259H, 274X, was proposed to result early truncated protein which was lack of the activity center site of P450C17, whereas missense mutation 7541 C>T causing A398V did not lie in the active site of the enzyme according to the computer model of human P450C17. The 46, XX case had irregular menstruation and slightly hypertension and hypokalemia. The ACTH stimulating test as well as the result of the sex hormones suggested that there was partial 17 alpha-hydroxylase/17, 20-lyase enzyme activities in the adrenal and sexual gland. We speculate that A398V might conserve partial of the enzyme's activities. The genotype was coincident with phenotype.

CONCLUSIONMore study should be done to have better understanding of the function of the mutated P450C17 enzymes.

Adrenal Hyperplasia, Congenital ; enzymology ; genetics ; Base Sequence ; DNA Mutational Analysis ; Exons ; genetics ; Female ; Heterozygote ; Humans ; Introns ; genetics ; Mutation ; Polymerase Chain Reaction ; Steroid 17-alpha-Hydroxylase ; genetics ; metabolism ; Young Adult

BACKGROUNDStatins and ezetimibe have been reported to change the balance of cholesterol metabolism, but few studies have been performed on Chinese patients. The aim of this study was to evaluate changes in cholesterol metabolism markers in patients with coronary heart disease.

METHODSForty-five patients with coronary heart disease were treated with 20 mg/d of simvastatin for four weeks. Subjects were then divided into two different therapy groups according to whether they reached the target values for total cholesterol and low density lipoprotein cholesterol level. Patients who reached the target values remained on simvastatin and those who did not reach the target values took a combination of simvastatin plus 10 mg/d ezetimibe until the 12th week. The concentrations of cholesterol synthesis markers (lathosterol and desmosterol) and absorption markers (campesterol and sitosterol) were measured on the 1st, 4th, and 12th week of the study by gas chromatography.

RESULTSAfter treatment with simvastatin for four weeks, the levels of total cholesterol and low density lipoprotein cholesterol decreased significantly compared to levels measured during the 1st week (P < 0.05). On the 12th week the levels of total cholesterol and low density lipoprotein cholesterol had decreased significantly (P < 0.001) compared to levels during the 4th week. By the 12th week the levels of campesterol and sitosterol in the combination group had decreased significantly (P < 0.05) compared with levels measured during the 4th week.

CONCLUSIONSCoronary heart disease patients with high cholesterol synthesis at baseline might gain a greater benefit from simvastatin treatment. Combination therapy with simvastatin plus ezetimibe in patients with low cholesterol synthesis at baseline might increase the success rate of lipid-lowering through decreasing the absorption of cholesterol.

Adult ; Aged ; Azetidines ; administration & dosage ; Cholesterol ; metabolism ; Cholesterol, LDL ; blood ; Coronary Disease ; drug therapy ; metabolism ; Drug Therapy, Combination ; Ezetimibe ; Female ; Humans ; Male ; Middle Aged ; Simvastatin ; administration & dosage

This study was purposed to investigate the effect of xbp-1 gene silencing on bortezomib-induced apoptosis in multiple myeloma cell line NCI-H929 (H929). After xbp-1 gene expression was interfered by small hairpin RNA, the cell apoptosis was assayed by flow cytometry with Annexin V-FITC/PI staining, and the expression level of XBP-1 protein was detected by Western blot. The results showed that XBP-1 protein level of H929 cells was inhibited effectively by the PLL3.7 lentiviral vector mediated expression xbp-1 shRNA. The apoptosis rate was significantly higher in xbp-1 shRNA-expressing cells than in untreated control group [(10.13±0.61)% vs (2.5±0.2)%, p<0.05]. After treatment with bortezomib, the apoptosis rate of XBP-1 protein functionally deficient H929 cells was significantly higher than those in vector control group [(45.07±1)% vs (19.53±0.8)%, p<0.05]. It is concluded that xbp-1 gene silencing can significantly enhance the pro-apoptotic activity of bortezomib in multiple myeloma cells.
Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Line, Tumor ; DNA-Binding Proteins ; genetics ; Gene Silencing ; Humans ; Multiple Myeloma ; genetics ; Pyrazines ; pharmacology ; RNA, Small Interfering ; genetics ; Regulatory Factor X Transcription Factors ; Transcription Factors ; genetics ; X-Box Binding Protein 1

The study was purposed to investigate the expression of CD73 on bone marrow nucleated cells (BMMNC) in various leukemia subtypes and its relationship with cell differentiation of leukemia. Immunocytochemistry staining and Wright-Giemsa staining of BMMNC from 75 cases of leukemia, 11 cases of myelodysplastic syndrome (MDS), 13 cases of non-leukemic patients and 9 healthy adults were performed, and the CD73(+) ratio in BMMNC and its relationship with differentiation of leukemia cells were analyzed. The results showed that the ratios of CD73(+) in BMMNC of com-B ALL, pre-B ALL and PLL were significantly higher than those in B-CLL (p < 0.05). CD73(+) ratios in AML subtypes of M(1), M(2a), t (8; 21), t (15; 17), M(4) and M(5) were markedly higher than those in MDS respectively, but in M(6) and MDS were lower and had no statistical difference between them. CD73(+) ratios in T-ALL, B-CLL, M(6), MDS, non-leukemia patients and healthy adults were close to each other and all of them were lower than those in B-ALL and other AML subtypes. It is concluded that the expression of CD73 is associated with leukemia subtype, differentiation and development. The higher differentiation of leukemia cells, the lower of CD73 expression in myeloid and B lymphoid leukemia, but T-ALL does not meet this pattern.
5'-Nucleotidase ; metabolism ; Adolescent ; Adult ; Cell Differentiation ; Humans ; Leukemia ; metabolism ; pathology ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; Leukemia, Myeloid, Acute ; metabolism ; Myelodysplastic Syndromes ; metabolism ; Young Adult

BACKGROUNDThis study transferred a recombinant gene encoding human insulin like growth factor-1 (hIGF-1) into modified primary skeletal myoblasts with a retroviral vector (pLgXSN) and determined whether the hIGF-1 promoted growth of skeletal muscle in rat.

METHODShIGF-1cDNA was amplified in vitro from normal human liver cells by using RT-PCR and cloned into plasmid vector pLgXSN. The recombinant vector pLghIGF-1SN and control vector pLgGFPSN were transfected into packaging cell PT67 and G418 was used to select positive colony. Myoblasts were infected with a high titre viral supernatant and transduction efficiency was evaluated as GFP expression. The expression of hIGF-1 mRNA in myoblasts was investigated by immunocytochemistry and RT-PCR. MTT assays detected the growth of myoblasts in vitro. Myoblasts transduced with pLghIGF-1SN were injected into hind limb muscles of 10 - 12 week male SD rats. Formed tissues were harvested 4 weeks later. Myocyte diameter, mean weight of hind limb and body were measured to evaluate the skeletal muscle growth.

RESULTSRecombinant retroviral plasmid vector pLghIGF-1SN was constructed successfully. The titre of the packaged recombinant retrovirus was 1 x 10(6) cfu/ml. The transfection rate of PT67 cells reached 100% after G418 screening. hIGF-1 expression was positive in myoblast-IGF-1. The proliferation rate of myoblast-IGF-1 in vitro was higher than GFP-myoblast or myoblast (P < 0.05). The mean weights of hind limb and body of rats injected myoblast-IGF-1 were higher than those of the rats injected with myoblast-GFP or myoblast (P < 0.05). Myocyte diameter had a significant increase in IGF-1 group compared to GFP group and myoblast group (P < 0.05).

CONCLUSIONSThe transfection of the human IGF-1 gene mediated by a retroviral vector can promote the growth of skeletal muscle in rats. Genetically modified primary skeletal myoblasts provide a possibly effective approach to treat some skeletal muscle diseases.

Animals ; Cells, Cultured ; DNA, Recombinant ; genetics ; Genetic Vectors ; Insulin-Like Growth Factor I ; genetics ; physiology ; Muscle, Skeletal ; growth & development ; Myoblasts ; physiology ; Rats ; Rats, Sprague-Dawley ; Retroviridae ; genetics ; Transfection

BACKGROUNDTissue-engineered bioartificial muscle-based gene therapy represents a promising approach for the treatment of heart diseases. Experimental and clinical studies suggest that systemic administration of insulin-like growth factor-1 (IGF-1) protein or overexpression of IGF-1 in the heart exerts a favorable effect on cardiovascular function. This study aimed to investigate a chronic stage after myocardial infarction (MI) and the potential therapeutic effects of delivering a human IGF-1 gene by tissue-engineered bioartificial muscles (BAMs) following coronary artery ligation in Sprague-Dawley rats.

METHODSLigation of the left coronary artery or sham operation was performed. Primary skeletal myoblasts were retrovirally transduced to synthesize and secrete recombinant human insulin-like growth factor-1 (rhIGF-1), and green fluorescent protein (GFP), and tissue-engineered into implantable BAMs. The rats that underwent ligation were randomly assigned to 2 groups: MI-IGF group (n = 6) and MI-GFP group (n = 6). The MI-IGF group received rhIGF-secreting BAM (IGF-BAMs) transplantation, and the MI-GFP group received GFP-secreting BAM (GFP-BAMs) transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups: S-IGF group (n = 6) and S-GFP group (n = 6). The S-IGF group underwent IGF-1-BAM transplantation, and S-GFP group underwent GFP-BAM transplantation. IGF-1-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats after two weeks of operation was performed. Four weeks after the treatment, hemodynamics was performed. IGF-1 was measured by radioimmunoassay, and then the rats were sacrificed and ventricular samples were subjected to immunohistochemistry. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine the mRNA expression of bax and Bcl-2. TNF-α and caspase 3 expression in myocardium was examined by Western blotting.

RESULTSPrimary rat myoblasts were retrovirally transduced to secrete rhIGF-1 and tissue-engineered into implantable BAMs containing parallel arrays of postmitotic myofibers. In vitro, they secreted consistent levels of hIGF (0.4 - 1.2 µg×BAM(-1)×d(-1)). When implanted into syngeneic rat, IGF-BAMs secreted and delivered rhIGF. Four weeks after therapy, the hemodynamics was improved significantly in MI rats treated with IGF-BAMs compared with those treated with GFP-BAMs. The levels of serum IGF-1 were increased significantly in both MI and sham rats treated with IGF-BAM. The mRNA expression of bax was lower and Bcl-2 expression was higher in MI-IGF group than MI-GFP group (P < 0.05). Western blotting assay showed TNF-α and caspase 3 expression was lower in MI-IGF group than MI-GFP group after therapy.

CONCLUSIONSrhIGF-1 significantly improves left ventricular function and suppresses cardiomyocyte apoptosis in rats with chronic heart failure. Genetically modified tissue-engineered BAMs provide a method delivering recombinant protein for the treatment of heart failure.

Animals ; Apoptosis ; Caspase 3 ; analysis ; Desmin ; analysis ; Genetic Therapy ; Heart Failure ; pathology ; physiopathology ; therapy ; Insulin-Like Growth Factor I ; genetics ; secretion ; Myoblasts, Skeletal ; metabolism ; Myocytes, Cardiac ; pathology ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; secretion ; Retroviridae ; genetics ; Tissue Engineering ; Tumor Necrosis Factor-alpha ; analysis ; Ventricular Function, Left

BACKGROUNDThere remains significant debate as to the relationship between fragmented QRS (fQRS) complexes on electrocardiogram (ECG) and acute myocardial infarction (AMI). Few studies have reported on this relationship in non-ST elevated AMI (NSTEMI), and thus, we attempt to assess this relationship and its potential short-term prognostic value.

METHODSThis was a single-center, observational, retrospective cohort study. A total of 513 consecutive patients (399 men, 114 women) with NSTEMI within 24 h who underwent coronary angiography at our department, between January 1, 2014, and December 31, 2014. Patients were divided into 2 groups according to the presence or absence of fQRS complex on the admission ECG. fQRS complexes were defined as the existence of an additional R' or crochetage wave, notching in the nadir of the S wave, RS fragmentation, or QS complexes on 2 contiguous leads. All patients were followed up for 6 months, and all major adverse cardiac events (MACE) were recorded.

RESULTSIn this study, there were 285 patients with fQRS ECG in the 513 patients with NSTEMI. The number of patients with 0-2 coronary arteries narrowed by ≥50% in fQRS group were less while patients with 3 narrowed arteries were more than in the non-fQRS group (P = 0.042). There were fewer Killip Class I patients in the fQRS group (P = 0.019), while Killip Class II, III, and IV patients were more in the fQRS group than in the non-fQRS group (P = 0.019). Left ventricular ejection fraction levels were significantly lower in the fQRS group (P = 0.021). Baseline total cholesterol, low-density lipoprotein, creatinine, creatine kinase, homocysteine, high-sensitivity C-reactive protein (CRP), and red blood cells distribution width levels were significantly higher in the fQRS group. Total MACE (MACE, P = 0.028), revascularization (P = 0.005), and recurrent angina (P = 0.005) were also significantly greater in the fQRS group. On final logistic regression analysis, after adjusting for baseline variables, the following variables were independent predictors of fQRS: Coronary artery narrowing (P = 0.035), Killip classification (P = 0.026), and total cholesterol (P = 0.002). The following variables were found to be independent predictors of preoperative MACE: Hemoglobin (P = 0.000), gender (P = 0.026), fQRS (P = 0.016), and time from myocardial infarction to balloon or coronary artery bypasses grafting (P = 0.013).

CONCLUSIONSThe fQRS complexes are commonly present in NSTEMI and the fQRS complexes are an independent predictor of MACE in NSTEMI patients. The number of narrowed coronary arteries, Killip classification, and total cholesterol are all independent predictors of the fQRS complexes.

Aged ; C-Reactive Protein ; analysis ; Electrocardiography ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Myocardial Infarction ; blood ; physiopathology ; Prognosis ; Retrospective Studies