Objective To investigate the effectiveness and safety of low-intensity warfarin anticoagulation in over 80-year-old patients with nonvascular atrial fibrillation (NVAF). Methods The 180 NVAF patients aged over 80 years were randomly assigned into 2 groups: 90 patients in lowintensity warfarin anticoagulation group (target value of INR 1.6-2.0), the other 90 patients in standard-intensity warfarin anticoagulation group (target value of INR 2. 0-3.0). All patients were followed up in outpatient-department for one year. Main outcome measures included the incidence rates of bleeding and thromboembolic events, and secondary outcome measures included the warfarin dosage and times of INR＞3.0. Results The incidence rate of thromboembolic events was 4.4% (4/90) in low-intensity group and 3.3% (3/90) in standard-intensity group with no statistically significant difference between these two groups (P＞0. 05). However, the incidence rate of hemorrhage was significantly lower in low-intensity group than in standard-intensity group [5.6% (5/90) vs. 16.7%(15/90), P＜0. 05]. Meanwhile the warfarin dosage was significantly lower in low-intensity group than in standard-intensity group [(1. 55±0. 63) mg vs. (2.31±0.57) mg, P＜0.05]. The times of INR＞3.0 were less in low-intensity group than in standard-intensity group (P＜0. 05). Conclusions Therapy with low-intensity warfarin anticoagulation in NVAF patients aged over 80 years may be equally effective as, but safer than that with standard-intensity warfarin.

Objective To explore the clinical value of genetic diagnosis of SMA,the homozygous deletion of survival motor neuron 1 (SMN1) gene in suspected spinal muscular atrophy (SMA) patients were analyzed in this study.Methods A total of 154 patients suspected with SMA and 20 healthy volunteers were recruited from January 2007 to December 2014 in the Genetic Diagnosis Center of the First People's Hospital of Yunnan Province and the Department of Neurology of the Fourth Affiliated Hospital of Kunming Medical University.Potential deletions in exons 7 and 8 of SMN1 gene were screened by use of polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method in both 154 patients suspected with SMA and 20 healthy volunteers.The frequencies of the deletions in exons 7 and 8 of SMN1 were calculated and statistical analysis of different deletion types among 3 SMA groups was performed with SPSS 13.0 software package.Results Among 154 suspected SMA patients,101 cases with homozygous deletions of exon 7 of SMN1 gene were detected,which accounted 65.6％ (101/154) of the suspected SMA patients.Among the 101 SMA patients,97.0％ (98/101) of the patients with both homozygous deletions of exons 7 and 8 for SMN1 gene and 3.0％ (3/101) of the patients with homozygous deletions of only exon 7 for SMN1 gene were detected.The patient with only deletion of exon 8 for SMN1 gene was notdetected.Four cases with negative results were subjected to be followed-up,but they were characteristic of SMA symptom by clinical re-visit.Thus,total 105 patients were confirmed with SMA,among them,68 were type Ⅰ SMA,27 were type Ⅱ SMA,and 10 were type Ⅲl SMA,which accounted for 64.8％ (68/105),25.7％ (27/105) and 9.5％ (10/105) of the SMA patients,respectively.Type Ⅳ SMA was not observed in these patients.No deletion was detected among 20 healthy volunteers.Conclusions PCR-RFLP assay is a noninvasive,simple,high sensitive and specific method for SMA diagnosis,which can be considered as the first-line genetic test for the suspected SMA patients.It will help to improve the accuracy of clinical diagnosis and the detection rate by strengthening the clinical diagnostic criteria and re-evaluating the suspected patients after negative genetic diagnosis.

Objective To investigate the effect of adenovirus-bone morphogenic protein 9 ( Ad-BMP9 ) on osteogenic differentiation of immortalized calvarial mesenchymal progenitor cells ( iCALs ) .Methods iCALs were infected with adenoviral vectors encoding BMP-9 or green fluorescent protein ( GFP) and the early osteogenic differentiation was assessed by detecting alkaline phosphatase (ALP) activity after being cultured for 3, 5 and 7 days.14 days after infection, alizarin red S staining was performed to study the formation of osteogenic calcium nodules .The expression of osteogenic marker genes Runx2 and OCN was assessed by quantitative real-time ( RT )-PCR and Western blotting .Results Significant increases in ALP activity and in the expressions of Runx 2 and OCN were detected in BMP-9 treated iCALs compared with GFP-treated cells(P<0.05).Meanwhile, alizarin red S staining showed that more mineralized nodules were found in the BMP-9 induced group .Conclusion BMP-9 can promote the osteogenic differentiation of iCALs .

Objective To compare the curative effect and safety of high-frequency and low-frequency repetitive tran-scranial magnetic stimulation(r-TMS) in the treatment of Parkinson's disease complicated with depressive disorder. Methods All 92 patients with Parkinson's disease complicated with depressive disorder were randomly allocated to three groups. High frequency group received antiparkinsonian drugs combined with high frequency r-TMS (5 Hz);Low frequency group received antiparkinsonian drugs combined with low frequency r-TMS (0.5 Hz);Sham group re-ceived antiparkinsonian drugs combined with sham r-TMS (s-rTMS). Each group received r-TMS twice a week for four weeks. UPDRS and HAMD-17 were assessed every two weeks , adverse events were recorded , and clinical global im-pression was carried out four weeks after the treatment. Results Upon enrollment, scores of HAMD and UPDRS among the three groups were not significantly different (P>0.05). During the second week of the intervention, the HAMD score in high frequency group improved significantly , and the differences between three groups were statistically signif-icant according to one-way ANOVA (P=0.0144). The differences changed larger in the fourth week, with greatly sig-nificant differences between the two groups (P=0.0000);During the second week of the intervention, the differences of UPDRSⅡscores in high frequency, low frequency and sham group were not statistically significant according to one-way ANOVA (P=0.1981). The differences appeared in the fourth week, but the differences between groups were not statistically significant according to one-way ANOVA (P=0.0219). During the second week and the fourth week of the intervention, UPDRS Ⅲ scores in the three groups were not significantly different (P=0.6105, 0.4248 respectively). Adverse events in the three groups were rare, and the differences were not statistically significant. Conclusion High-frequency stimulation on dorsal-lateral left prefrontal cortex is effective in alleviating depression for patients with Parkinson's disease, and is also effective in improving capabilities in daily life, which shows exact clinical effect and rare adverse events.

OBJECTIVE: To perform carrier screening for spinal muscular atrophy (SMA) among 3049 reproductive-age individuals from Yunnan region and determine the copy number of survival motor neuron (SMN) gene and carrier frequencies. METHODS: Multiplex ligation-dependent probe amplification (MLPA) was used to determine the copy number of exon 7 of SMN1 and SMN2 genes and identify those with a single copy of SMN1 gene. Prenatal diagnosis was performed for couples whom were both found to be SMA carriers. RESULTS: In total 62 SMA carriers were identified among the 3049 subjects, which yielded a carrier frequency of 1 in 49 (2.03%). No statistical difference was found in the carrier frequency between males and females (1.91% vs. 2.30%, P>0.05). Respectively, 1.3% (41/3049) and 0.69% (21/3049) of the carriers were caused by heterozygous deletion and conversion of the SMN1 gene. The average copy number for SMN1 alleles was 1.99. Two couples were found to be both as SMA carriers, for whom the birth of an affected fetus was avoided by prenatal diagnosis. CONCLUSION No difference was found in the carrier frequency of SMA-related mutations between the two genders in Yunnan region, which was in keeping to an autosomal recessive inheritance pattern. Determination of the carrier frequency for SMA and SMN gene variants may provide a basis for genetic counseling and prenatal diagnosis for the disease.
China ; Female ; Genetic Carrier Screening ; Genetic Counseling ; Genetic Variation ; Heterozygote ; Humans ; Male ; Muscular Atrophy, Spinal ; genetics ; Pregnancy ; Prenatal Diagnosis ; Survival of Motor Neuron 1 Protein ; genetics ; Survival of Motor Neuron 2 Protein ; genetics

OBJECTIVETo establish a strategy for screening and diagnosing common microdeletion and microduplication syndromes among children with idiopathic mental retardation and development abnormalities.

METHODSPotential chromosomal variations among patients with unexplained mental retardation, cardiac anomalies, particular facial features, learning disabilities and other clinical characteristics were detected with bacterial artificial chromosome BACs-on-Beads (BoBs) technique and karyotyping. Positive results were verified with array-based comparative genomic hybridization (Array-CGH).

RESULTSFifty eight of the 60 patients had a normal chromosome karyotype. Ten patients with microdeletion and microduplication syndromes were detected by BoBs, which included two positive cases identified through chromosome karyotyping. Two patients were respectively diagnosed as Smith-Magenis syndrome and Prader-Willi/Angelman syndrome by BoBs and the results were confirmed by Array-CGH.

CONCLUSIONBoBs is capable of detecting chromosome microdeletion and microduplication with high specificity and throughput, which can compensate the shortcomings of conventional cytogenetic technology and will be widely applied for clinical diagnosis.

Adolescent ; Child ; Child, Preschool ; Chromosome Deletion ; Chromosome Duplication ; Chromosomes, Artificial, Bacterial ; genetics ; Comparative Genomic Hybridization ; Cytogenetic Analysis ; methods ; Female ; Humans ; Infant ; Infant, Newborn ; Karyotyping ; Male ; Oligonucleotide Array Sequence Analysis

OBJECTIVETo investigate the mutations of phenylalanine hydroxylase (PAH) gene in 20 phenylketonuria (PKU) patients from Yunnan.

METHODSThe 13 exons and the splicing regions of 12 introns of the PAH gene were sequenced to detect mutations in 20 unrelated PKU patients.

RESULTSPAH gene sequencing has revealed 15 types of mutations, in which the most frequently mutation was p.R243Q (30.0%), followed by p.Y356X(10.0%), p.R111X (7.5%), IVS4+2T>A (7.5%) and p.V399V (7.5%). Exons 7, 11, 3 and introns 4, 11 were most frequently involved. Six novel mutations, including c.59A>C, c.60G>C, c.690_691insG, c.1119_1120insT, c.441+2T>A, c.842+4A>T and c.1200+1T>G were detected.

CONCLUSIONPAH gene mutations identified in Yunnan are more similar to those of northern China, with R243R being the most common, though there are still certain characteristics for the type and frequency of mutations.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; China ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Phenylalanine Hydroxylase ; genetics ; Phenylketonurias ; enzymology ; genetics ; Young Adult

OBJECTIVETo provide genetic analysis for a pregnant woman with chromosomal translocations and intellectual disability, and to provide prenatal diagnosis for her fetus.

METHODSRoutine G-banding was performed to analyze the karyotypes of the woman and her fetus. Copy number variants were determined with array comparative genomic hybridization (array-CGH).

RESULTSThe pregnant woman has carried an apparently balanced translocation involving chromosomes 1, 2, 6 and 7, with a karyotype of 46, XX, t(1;2) (p22;p23), t(6;7) (q21;p15). The karyotype of her fetus was ascertained as 46, XY, t(6;7) (q21;p15) mat. Array-CGH has detected a 4 Mb microdeletion at 6q22.1-q22.31 (115 311 507-119 332 956) in both individuals. As the 6q22.1-q22.31 microdeletion may be associated with the main clinical manifestations of the woman, the family decided to terminate the pregnancy. The fetus was male and appeared to have no obvious abnormality.

CONCLUSIONPrenatal diagnosis for pregnant women with translocations and mental retardation is a challenging task. Combined application of cytogenetic analysis and array-CGH may facilitate the diagnosis and genetic counseling.

Adult ; Female ; Fetus ; abnormalities ; Genetic Testing ; methods ; Humans ; Intellectual Disability ; genetics ; Male ; Pregnancy ; Prenatal Diagnosis ; methods ; Translocation, Genetic ; genetics ; Young Adult