Objective To evaluate the prognosis and safety of long-term oral Branched-Chain Amino Acids (BCAAs) for patients with cirrhosis.Methods Randomized controlled trials (RCTs) were identified from CBM (between January 1978 and September 2013),CNKI (between January 1979 and September 2013),PubMed (between January 1970 and September 2013),EMBASE (between January 1970 and September 2013),and Cochrane Library (issue 4,2013).Publications of the RCTs on the treatment of cirrhosis with oral BCAAS were included and analyzed according to the criteria of Cocbrane handbook.Results Six RCTs involving 1 047 patients were included.The results showed that oral BCAAs improved the event-free survival when compared with the control group [RR =1.13,95％ CI =(1.05,1.23),P =0.001].BCAAs supplements had no effect on mortality or had no definite effect on the deteriorative rate of minimal hepatic encephalopathy (MHE) or quality of life (QOL).As reported in some trials,the main side effects of BCAAs were gastrointestinal symptoms.Conclusions Long-term oral BCAAs may improve event-free survival in cirrhotic patients.However,no definite conclusion can be made without evidences from larger,randomized,double-blind,placebo-controlled,and multicenter trials.

Objective To identify the risk factors associated with cardiovascular and cerebrovascular disease (CCVD) in maintenance hemodialysis (MHD) patients. Methods We analyzed all of the patients undergoing maintenance hemodialysis in the dialysis center of the 3rd Affiliated Hospital of Sun Yat-sen University for at least 3 months from Jan 1st, 2009 to Dec 31st, 2014. Baseline and yearly interval clinical data were recorded and patients were followed up until morbidity or death of CCVD. Cox proportional hazard regression and time-dependent Cox regression were used to estimate the relative risk of outcomes associated with clinical measurements. Results There were 243 patients enrolled in the study, with a mean age of (53.2 ± 16.4) years old, and 138 of them were male (56.8%). The multivariate Cox proportional model revealed that age (HR=1.040, 95%CI:1.015-1.065, P=0.002), Erythropoietin (EPO) dose (HR=0.914, 95%CI: 0.846-0.987, P=0.022) and history of cardiovascular and cerebrovascular disease (HR=4.045, 95%CI: 2.074-7.890, P<0.001) were independent predictors of CCVD in MHD patients. After adjusting for baseline predictors, time-dependent serum phosphorus level (HR=1.722, 95%CI: 1.034-2.866, P=0.037) was significantly associated with CCVD. Conclusion Older age, decreases in EPO dose and history of cardiovascular and cerebrovascular disease were associated with increased risks of CCVD in MHD patients. Increase in serum phosphorus level was associated with increased risks of CCVD in a time-dependent manner.

OBJECTIVE: To explore the genetic basis for a child affected with cerebral creatine deficiency syndrome 1 (CCDS1). METHODS: High-throughput sequencing was carried out to screen pathogenic variant associated with the clinical phenotype of the proband. The candidate variant was verified by Sanger sequencing. RESULTS: High-throughput sequencing revealed that the proband has carried heterozygous c.327delG variant of the SLC6A8 gene, which was verified by Sanger sequencing.Neither parent was found to carry the same variant. CONCLUSION The de novo heterozygous c.327delG variant of the SLC6A8 gene probably underlay the CCDS1 in this child.
Brain Diseases, Metabolic, Inborn/genetics* ; Creatine ; Genetic Testing ; Heterozygote ; Humans ; Mental Retardation, X-Linked ; Mutation

OBJECTIVE: To explore the genetic etiology of a fetus with autosomal recessive polycystic kidney disease (ARPKD). METHODS: Prenatal ultrasonography has revealed oligohydramnios and abnormal structure of fetal kidneys. After careful counseling, the couple opted induced abortion. With informed consent, genomic DNA was extracted from the muscle sample of the abortus and peripheral blood samples of the couple. High throughput whole exome sequencing was carried out to detect potential variants in relation with the disease. Suspected variants were verified by Sanger sequencing. RESULTS: Prenatal ultrasound revealed increased size of fetal kidneys, with multiple hyperechos from the right kidney, and multiple hyperechos with anechoic masses within the left kidney. DNA sequencing revealed that the fetus has carried heterozygous variants of the PKHD1 gene, including c.7994T>C inherited from its father, and two heterozygous variants of the PKHD1 gene c.5681G>A from its mother. CONCLUSION The compound heterozygous c.7994T>C and c.5681G>A variants of the PKHD1 gene probably underlay the pathogenesis of ARPKD in this fetus. Above results can provide guidance for subsequent pregnancies of the couple.
Female ; Fetus ; Genetic Testing ; Humans ; Mutation ; Polycystic Kidney, Autosomal Recessive/genetics* ; Pregnancy ; Receptors, Cell Surface/genetics*

OBJECTIVE: To carry out genetic testing for an abortus suspected with Cornelia de Lange syndrome (CdLS). METHODS: History of gestation and the family was taken. Combined with prenatal ultrasonography and the phenotype of the abortus, a diagnosis was made for the proband. Fetal tissue and peripheral blood samples of its parents were collected for the extraction of genomic DNA. Whole exome sequencing was carried out to detect mutations related to the phenotype. Suspected mutations were verified in the parents through Sanger sequencing. RESULTS: Prenatal ultrasound found that the forearms and hands of the fetus were anomalous, in addition with poorly formed vermis cerebellum, slight micrognathia, and increased echo of bilateral renal parenchyma. Examination of the abortus has noted upper limb and facial malformations. Whole exome sequencing revealed that the fetus carried a heterozygous c.2118delG (p.Lys706fs) frameshift mutation of the NIPBL gene. The same mutation was not found in either parent. CONCLUSION The heterozygous c.2118delG (p.Lys706fs) frameshift mutation of the NIPBL gene probably underlies the CdLS in the fetus. Above finding has provided a basis for the genetic counseling for the family.
Cell Cycle Proteins/genetics* ; DNA Mutational Analysis ; De Lange Syndrome/pathology* ; Female ; Fetus ; Humans ; Male ; Mutation ; Phenotype ; Pregnancy ; Whole Exome Sequencing

Objective To establish a rapid method for the clinical detection and identification of fungi in clinical urine samples.Methods DNA was extracted from clinically collected urine sample,and the fungal ribosomal internal transcribed spacer was amplified by polymerase chain reaction (PCR) and followed by pyrosequencing.The fungal species were identified by sequence alignment.Results The identification results were compared between PCR-pyrosequencing and conventional culture method.Among the 1320 urine samples,180 were detected positive by conventional method with the positive rate of 13.6％,while 192 were positive by the pyrosequencing based method with the positive rate of 14.5％.The overall coincidence rate of the two methods was 99.09 ％,with the positive coincidence rate of 100 ％ and the negative coincidence rate of 98.95 ％.The Kappa value was 0.963,suggesting a good consistency.The results of 13 standard strains were consistent with the actual results.Conclusions A rapid culturefree method for the detection of fungi in urine sample has been successfully established.This method is based on PCR-pyrosequencing technology with highly accuracy,sensitivity and reproducibility.It is highly automated,cost effective and with high throughput (96 samples per run).The fungal pathogen in urine is identified by single step test within 3 hours without conventional culture.Thus,it is applicable in the clinical laboratory.

Objective:To confirm the transportation and evaporation efficiency of micro droplets sprayed by high-pressure nozzles from purified tritium-containing wastewater with carrier gas in the horizontal evaporation chamber.Methods:A scale test bench with a single high-pressure nozzle had been built based on design conditions and similarity criteria to explore the designed evaporation characteristics of generated micro droplets in the horizontal evaporation chamber. At the same time, combined with experimental data, a suitable evaporation model was constructed using the Discrete Phase Model (DPM) in Ansys Fluent. On this basis, further simulation and analysis were conducted on the evaporation process and efficiency under the condition of multiple nozzles in the desighed horizontal evaporation chamber.Results:For single nozzle tests, the particle size of micro droplets along the nozzle centerline was between 12-50 μm and the particle size distribution was similar to the Rosin-Rammler distribution. Besides, the relative light intensity decreased exponentially with distance, indicating that the particle size and concentration of micro droplets both decreased rapidly, which means the evaporation rate of micro droplets was rapid. For the simulation of multiple nozzles injection in the desighed horizontal evaporation chamber, even for the hardest design condition, the evaporation percentage reached up to 99%, and small amount of the escaping micro droplets continued to evaporate during the process of mixing with other process exhaust until complete evaporation in the vertical chimney section.Conclusions:Under the conditions of desighed sprayed particle size distribution, typical operating conditions and the incoming flow similar to the supposed area, the complete evaporation of the micro droplets can be basically achieved in the horizontal evaporation chamber, so as to ensure the complete evaporation of purified tritium-containing wastewater from the outlet of the chimney.

OBJECTIVE: To explore the prenatal ultrasonographic features and genetic basis for an abortus suspected for type II Cornelia de Lange syndrome (CdLS2). METHODS: A fetus diagnosed with CdLS2 at the Shengjing Hospital Affiliated to China Medical University on September 3, 2019 was selected as the study subject. Clinical data of the fetus and family history was collected. Following induced labor, whole exome sequencing was carried out on the abortus. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: Prenatal ultrasonography (33 weeks of pregnancy) has revealed multiple anomalies in the fetus, which included slightly widened cavity of septum pellucidum, blurred corpus callosum, slightly reduced frontal lobe volume, thin cortex, fusion of lateral ventricles, polyhydramnios, small stomach bubble, and digestive tract atresia. Whole exome sequencing has revealed a heterozygous c.2076delA (p.Lys692Asnfs*27) frameshifting variant in the SMC1A gene, which was found in neither parent and was rated as pathogenic based on the guidelines of American College of Medical Genetics and Genomics (ACMG). CONCLUSION The CdLS2 in this fetus may be attributed to the c.2076delA variant of the SMC1A gene. Above finding has provided a basis for genetic counseling and assessment of reproductive risk for this family.
Pregnancy ; Female ; Humans ; Cell Cycle Proteins/genetics* ; De Lange Syndrome/diagnosis* ; Phenotype ; Ultrasonography, Prenatal ; Fetus/diagnostic imaging* ; Mutation

OBJECTIVE: To apply nanopore third-generation sequencing for the detection of chromosomal aneuploidy samples, and explore its performance and application prospects. METHODS: DNA extracted from two human cell lines with X chromosome monosomy and 22.5 Mb deletion in 7q11.23-q21.3 region was sequenced with a MinION sequencer, and the results were analyzed. RESULTS: Respectively, 555 872 and 2 679 882 reads were obtained from the two samples within 24 hours, with genome coverage being 53.75% and 88.63%. With a sequencing depth of 0.81× and 2.40× , respectively, the abnormal chromosomal regions could be detected by comparative analysis using Minimap2. CONCLUSION With low-depth whole genome sequencing, the use of nanopore third-generation sequencing is expected to complete the detection and analysis of chromosomal aneuploidy samples within 24 hours, but its further application and promotion needs to overcome the cost constraints.
Aneuploidy ; Chromosomes ; High-Throughput Nucleotide Sequencing ; Humans ; Sequence Analysis, DNA ; Technology

OBJECTIVE: To explore the nature and origin of chromosomal copy number variants (CNVs) in a pedigree affected with mental retardation. METHODS: Genomic CNVs of the proband were analyzed by next generation sequencing (NGS). Chromosomal karyotypes of the proband and his relatives were analyzed with high-resolution karyotyping and fluorescence in situ hybridization (FISH). RESULTS: Clinical phenotypes of the proband and other patients from the pedigree included mental retardation and mild dysmorphism. The results of NGS revealed that the proband carried a 16.24 Mb microduplication at 4p16.3-15.32 and a 2.2 Mb microdeletion at 8p23.3-23.2. Other patients of the pedigree harbored the same variants, while those without the phenotypes did not harbor the variants. The results of high-resolution karyotyping and FISH revealed that the mother of the proband carried a reciprocal translocation between 4p and 8p, and her karyotype was 46,XX,t(4;8)(p16;p23). No karyotypic abnormality was detected in his father. CONCLUSION The abnormal phenotypes of this pedigree may be attributed to 4p microduplication in conjunct with 8p microdeletion derived from a maternal balanced translocation between 4p and 8p.
Chromosome Aberrations ; Chromosome Duplication ; Chromosomes, Human, Pair 4 ; Chromosomes, Human, Pair 8 ; Female ; Genetic Testing ; Humans ; In Situ Hybridization, Fluorescence ; Intellectual Disability ; genetics ; Karyotyping ; Pedigree ; Phenotype