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

OBJECTIVETo investigate the CYP17A1 gene mutations in Chinese patients with 17 alpha-hydroxylase/17, 20-lyase deficiency.

METHODSClinical data were retrospectively analyzed. The CYP17A1 gene mutations were detected in 5 cases with 17 alpha-hydroxylase/17, 20-lyase deficiency and their relatives. The genomic DNA of the patients 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 sequenced. Sequencing results were compared to the established human CYP17A1 sequence.

RESULTSBriefly, we found 2 kinds of compound mutations, of which were: (1) 6436-6438(TAC-->AA), causing amino acid Y329K, 418X; (2) 6531-6532(GC-->A), causing amino acid L361F, 418X. Among the five cases, four were homozygous for 6436-6438(TAC-->AA), whereas one was compound heterozygous for 6436-6438(TAC-->AA)/6531-6532(GC-->A). The clinical characteristics of 5 cases were all completely combined defects of 17 alpha-hydroxylase/17, 20-lyase, and they all carried two alleles of CYP17A1 gene mutations that all shifted the reading frame and resulted in truncated protein which lack of the activity center site of P450C17, of which corresponding with their clinical feature.

CONCLUSIONNine alleles have the mutation of 6436-6438(TAC-->AA), accounting for 90% of total alleles (9/10). That suggests this kind of mutation may have racial specificity. More study should be done to have better understanding of the function of the truncated P450C17 enzymes.

Adolescent ; Adrenal Hyperplasia, Congenital ; enzymology ; genetics ; Alleles ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; DNA ; DNA Mutational Analysis ; DNA Primers ; Exons ; genetics ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Point Mutation ; Polymerase Chain Reaction ; Sexual Infantilism ; genetics ; Steroid 17-alpha-Hydroxylase ; genetics ; metabolism ; Young Adult

OBJECTIVEIn this study, a growing rat model of zinc deficiency was established to investigate the effect of zinc deficiency on intestinal mucosal morphology and digestive enzyme activity as well as to provide a scientific basis for zinc supplementation therapy in patients with diarrhea.

METHODThree-week-old weaned Sprague-Dawley male rats (n = 30) were randomly divided into 3 groups with 10 in each: rats in the control group (ZA) were fed with a normal diet containing 30 µg/g zinc; rats in the zinc deficient group (ZD) were fed with a zinc-deficient diet containing 0.4 µg/g zinc (refer to AIN-76 formula); and rats in the paired fed group (PF) were fed with a normal diet, but the food intake was limited to intake of rats in ZD group in the previous day. All rats were provided with deionized water for drinking. Their body weight was measured and the food intake during the previous day was recorded early in the morning of the following day. Symptoms of zinc deficiency, such as anorexia, diarrhea, dermatitis, and growth retardation, were observed. Two weeks later, the rats were sacrificed and serum zinc concentration was measured. Jejunal mucosa was taken for biopsy and was stained with hematoxylin and eosin (HE). The height ratio of the jejunal mucosal villi and crypts was measured. In addition, the activity of lactase in the jejunal mucosal brush border, γ-glutamyl peptidase (GGT), and aminopeptidase N (APN) were measured.

RESULTThe average weight of the rats in the ZA, ZD, and PF groups at the beginning of the experiment was (67.4 ± 5.3) g, (64.7 ± 4.8) g, and (66.5 ± 4.1) g, respectively, and the average daily food intake was (11.2 ± 1.0) g, (11.6 ± 1.6) g, and (11.2 ± 1.4) g, respectively. The intergroup differences were not significant. On the 7(th) day of experiment, no significant differences in average food intake were observed between the ZD group and the ZA and PF groups, but the average body weight in the ZD group was significantly lower than that in the ZA and PF groups (P < 0.01). At the end of the experiment (2 weeks), the average weight in the ZD group (112.0 ± 11.5) g was significantly lower than that in the ZA (164.0 ± 15.9) g and PF groups (137.5 ± 16.2) g. The average food intake in the ZD group (13.4 ± 5.1) g was significantly lower than that in the ZA group (18.2 ± 2.4) g (P < 0.01). Serum zinc level in the ZD group (733 ± 231) µg/L was significantly lower than that in the ZA (1553 ± 159) µg/L and PF groups (1457 ± 216) µg/L (P < 0.01). The height ratio of jejunal mucosa villus and crypt in the ZA, ZD, and PF groups was 2.98 ± 0.5, 2.77 ± 0.5, and 2.81 ± 0.7, respectively, and lactase activity was (26.1 ± 15.0) U/mg, (27.4 ± 12.8) U/mg, and (40.8 ± 18.5) U/mg, respectively, without significant intergroup differences. The GGT activity in the jejunal mucosa in the ZD group (12.7 ± 6.5) U/g was significantly lower than that in the ZA (19.1 ± 10.4) U/g and PF groups (18.5 ± 7.7) U/g, but the difference was not significant. The activity of APN in the jejunal mucosa in the ZD group (25.5 ± 7.5) U/g was significantly lower than that in the ZA (48.7 ± 16.8) U/g and PF groups (43.9 ± 14.5) U/g (P < 0.01).

CONCLUSIONZinc deficiency can cause loss of appetite, weight loss, and decreased activity of peptidase in the jejunal mucosal brush border. Zinc deficiency has little effect on the height ratio of the villus and crypt and lactase activity, thereby indicating that zinc deficiency may first affect protein digestion and absorption.

Animals ; Intestinal Mucosa ; enzymology ; metabolism ; pathology ; Jejunum ; metabolism ; pathology ; Lactase ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Zinc ; deficiency