As one of the most serious hereditary neuromuscular disease, spinal muscular atrophy (SMA) is caused by the loss or mutation of survival motor neuron 1 (SMN1) gene. It leads to a decrease in the level of SMN protein and a consequent loss of alpha neurons and progressive muscle atrophy resulting in the progressive muscle weakness, the significant disability and the shortened lifespan. Up till now, only three drugs have been approved for SMA, including the gene therapy drug onasemnogene abeparvovec. The antisense oligonucleotide drug nusinersen and and the small molecule chemical drug risdiplam were briefly introduced. Some representative samples of the small molecule chemical drugs and antisense oligonucleotide drugs targeting SMN2 in the clinical trial or preclinical research phases were also reviewed.

Adolescent ; Adult ; Angiography, Digital Subtraction ; Child ; Decompression, Surgical ; methods ; Female ; Humans ; Magnetic Resonance Angiography ; Male ; Middle Aged ; Optic Nerve Injuries ; diagnostic imaging ; pathology ; Young Adult

Objective To establish human choriocarcinoma JeG-3 cell line resistant to floxuridine (FUDR)and describe the characteristics of this FUDR-resistant subline.The thymidylate synthase (TS) expression level in FUDR-resistant subline was also discussed.Methods The FUDR-resistant sub-line JeG-3/FUDRA was established by intermitted exposure to grads increased FUDR.Reversed microscope was used to observe the morphological changes in FUDR-resistant sub-line.Population doubling time was calculated and compared based on the growth curve of these two cell lines,cell cycles and chromosomal ploidy were assayed with flow cytometry methods.The chemo-luminescence assay was used to detect the hormone secretion by two kinds of cell lines.The resistant index (RI) was measured by cell counting kit-8 (CCK-8)assay.Quantitative RT-PCR was used to detect the mRNA expression level of TS and we also detected the TS mRNA expression level in different doses exposed subline.Results The RI of JeG-3/FUDRA was 31.62.Compared with the JeG-3 cell,the FUDR-resistant cell line had gross changes in morphological,cell growth,cell cycles and chromosomal numbers.The ability of human chorionic gonadotrop(hCG) and progesterone secretion was lower in JeG-3/FUDRA subline.The trend of TS mRNA expression was:while exposed to low concentration of FUDR,the TS mRNA expression level was downregulated,then followed the increasing dose of the drug,the expression level of TS mRNA ascended gradually.When the terminal concentration was reached,the expression level of TS mRNA in JeG-3/FUDRA subline was higher than that of JeG-3 cell line (P＜0.05).Conclusions We established the FUDR-resistant subline of JeG-3 successfully.The TS mRNA expression level is stage-related to the different concentration and different phase in FUDR exposure.Our data suggested that TS mRNA expression level may not be used as a biomarker to predict the chemosensitivity in FUDR-based chemotherapy.

Objective:To obtain a large amount of erythromycin B and to investigate the activity site in eryK. Methods:The key sequence of the BC loop region in eryK gene was knocked out and the eryK gene with 101 bp deleted was amplified by overlapping PCR,and cloned into vector pWHM3 to construct recombinant plasmid. The Saccharopolyspora erythraea mutant AK17 was constructed through chromosomal homologous recombination technique.Results and Conclusions:The S.erythraea mutant AK17 was constructed. The results of TCL and MS analysis showed that the major fermentation product of AK17 is erythromycin B.

Adult ; Air Pollutants ; adverse effects ; Humans ; Male ; Military Medicine ; Monitoring, Physiologic ; Noise, Occupational ; adverse effects

BACKGROUNDAlternatives to the conventional auro-galvanoforming ceramic bridge need to be evaluated in long-term longitudinal studies before being recommended for restoration of dentition defects. This study aimed to evaluate the clinical performance of a ceramic bridge with auro-galvanoforming primary coping and Ni-Cr pontic for restoration of dentition defects.

METHODSIn total, 114 ceramic bridges with auro-galvanoforming (primary coping and Ni-Cr pontic) were placed in 112 patients with dentition defects. Among them, 83 bridges in 82 patients were available for follow-up after 7 years. We evaluated marginal integrity, color match, gingival inflammation, fracture of ceramic bridges, and recurrent caries.

RESULTSMarginal integrity of the ceramic bridges was perfect in all patients. Most ceramic bridges maintained their original color. Fracture was found in three bridges; the rest were free of fracture, breakage, and loosening. Recurrent abutment caries were not found. Ceramic bridges with auro-galvanoforming (primary coping and Ni-Cr pontic) produced satisfactory clinical outcomes - equivalent to the conventional porcelain-fused-to-metal restoration. This technique is especially useful for dentition defects of the molar area and is cheaper than restoration with noble metal bridges.

CONCLUSIONSCeramic bridges with auro-galvanoforming (primary coping and Ni-Cr pontic) performed well for the restoration of dentition defects during this follow-up period. More studies are warranted to further evaluate this technique as an alternative to the conventional porcelain-fused-to-metal restoration.

Adult ; Aged ; Cementation ; Ceramics ; Dental Materials ; Dental Occlusion ; Dental Prosthesis ; methods ; Denture Design ; Denture, Partial, Fixed ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Young Adult

Objective To summarize the experience of minimally invasive treatment in upper ureteral calculi complicated with urinary tract infection.Methods Retrospectively analyzed the clinical data of 40 cases with upper ureteral calculi complicated with urinary tract infection who were treated from December 2009 to December 2013.Results Twenty-one cases were performed with retrograde catheterization at cystoscopy and 11 cases were performed with percutaneous nephrostomy directed by B-ultrasound in the stage Ⅰ,the infection were controlled after operation 2-6 d.These patients were successfully cured by extracorporeal shock-wave lithotripsy (ESWL),ureterorenoscope lithotripsy (URL) or percutaneous nephrolithotomy (PCNL) in the stage Ⅱ].The remaining 8 cases were successfully cured by URL with antiinfection therapy in the stage Ⅰ.All patients had no ureteral perforation,laceration,urine derived sepsis and severe bleeding complications.All of ureteral calculi were drained after 2-10 weeks.The average hospital stay was 13.4 d.Patients were followed up for 1-12 months after the stone expulsion,the average was 6 months.There was 3 patients who with preoperative renal dysfunction had been improved after URL,and other patients' renal function returned to normal.Conclusions The therapy of retrograde catheterization at cystoscopy and percutaneous nephrostomy directed by B-ultrasound in the stage Ⅰ,combined with ESWL,URL or PCNL in the stage Ⅱ in treating upper ureteral calculi complicated with urinary tract infection have more advantage such as less complication,rapid control of infection and complete removal of stones.It is an ideal method.

BACKGROUNDPost and post-core systems are used to restore extensively damaged teeth. Among these systems, cast alloy post and core, prefabricated threaded alloy post and prefabricated simple alloy post are most frequently applied in China nowadays. In Europe and North America a combined application of the fiber post, resin-core and crown has been applied to restore seriously destructed teeth with satisfactory results in recent years. This study was intended to evaluate the clinical effect of carbon fiber post system on restoration of child anterior tooth defect after root canal therapy, based on 3 - 5 years' observation.

METHODSOne hundred and six children with incompletely established occlusion were observed and followed for an average of 42 months (ranging from 36 to 60 months). Eighty-five upper teeth and forty-one lower teeth were restored with carbon fiber post system and composite jacket crown. Periodic check-up was conducted for periodontal condition and restoration effect.

RESULTSOne hundred and twenty-one (96.2%) restorations were successful. Four jacket crowns (3.0%) were lost. One tooth (0.8%) had slight gingival inflammation. Tooth root or post fracture and gingival stain were not observed. X-ray showed there was no obvious change in aspects including the width of periodontal membrane, the density of alveolar bone and the height of alveolar ridge crest.

CONCLUSIONSCarbon-fiber post system can satisfy the clinical requirements of young patients who have residual anterior crown and root caused by trauma or caries, and have incomplete occlusion and have completed root canal therapy. This system helps realize good esthetic result for patients and easy practice for dentists. Carbon fiber post is safe and convenient, especially for sick children.

Adolescent ; Carbon ; Child ; Dental Restoration, Permanent ; Humans ; Post and Core Technique ; Root Canal Therapy

Tumor cell energy metabolism is dependent on glycolysis and oxidative phosphorylation.Tumor cells,because of its rapid growth,often show increased intake of glucose and other nutrients,increased glycolysis and so on.In recent years,the study on energy metabolism of tumor cells has received extensive attention.This paper summarizes the required nutrients,regulatory networks and therapeutic targets in the energy metabolism of tumor cells,and provides important reference for future research and clinical treatment.

Background Age-related macular degeneration (AMD) is a heritable,progressive degenerative disorder that triggers central visual impairment.Research demonstrated that the single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor 1 (VEGFR1) gene is associated with AMD in different population.However,the results varied among diversified ethnic origin composition and distinct regions.Objective This study was to investigate the associations between the SNPs of VEGFR1 genetic variants along with smoking exposure and the risk of AMD in Hui and Han ethnics in the Ningxia population in China.Methods A case-control study was conducted.Four hundreds and thirty-two AMD patients including 325 Han ethnic patients and 107 Hui ethnic patients were recruited from March 2011 to June 2015,and 906 ethnicity-and gender-matched age-related cataract patients were contemporaneously recruited as control group,including 698 Han ethnic patients and 208 Hui ethnic patients.Periphery blood sample of 5 ml was collected from the subjects and genomic DNA was prepared.Eight tagging SNPs loci were acquired to cover rs2281827,rs3936415,rs7337610,rs7981680,rs9554320,rs9554322,rs9582036 and rs9943922,and the genotypes of SNPs were detected by using MassARRAYTM time-of-flight mass spectrometry system.Chi-square test and multi-factor Logistic regression analysis were utilized to estimate the discrepancy of allele frequency and genotype distribution in Hui and Han AMD patients.Moreover,the correlation of AMD with smoking and age statue were further analyzed.This study protocol complied with Helsinki Declaration and was approved by Ethic Committee of Ningxia Eye Hospital.Written informed consent was obtained before any relevant medical examination.Results There were significant differences in the age between AMD group and control group in both Han and Hui ethnicity (Han:P =0.000;Hui:P =0.009).The smoking exposure was significantly different between AMD group and control group in Han ethnicity (P =0.000),and smoking was the independent risk factor of AMD disease in Han ethnicity of N ingxia region (odds ratio [OR] =2.622,95％ confidence interval [CI]:1.899-3.619).The allele frequencies of SNPs were not significantly different in the AMD patients between Han and Hui ethnicity (all at P＞0.05).However,the allele frequencies and genotype distribution of rs7337610 and rs9554322 SNPs were significantly different between the AMD group and control group in both Han and Hui ethnicity (all at P=0.00).The genotype distribution of rs9582036 and rs9943922 SNPs was significantly different between the AMD group and control group in Han ethnicity (P=0.02,0.00).Allelic G of rs7337610 was the protective factor of AMD disease in Han and Hui ethnieity (OR=0.354,95％ CI:0.288-0.435;OR=0.446,95％ CI:0.315-0.632),while allelic C of rs9554322 was the risk factor of AMD disease in Han and Hui ethnicity (OR=1.671,95％ C1:1.234-2.262;OR=3.661,95％ CI:2.156-6.218).Allelic A of rs9582036 was the risk factor of AMD disease in Han ethnicity (OR =1.477,95％ CI:1.124-1.940).Conclusions Smoking is the independent risk component for Han population with AMD.Of the eight SNPs tagged,the genotypes and alleles of rs9554322 and rs7337610 seems to confer susceptibility to AMD in both Han and Hui ethnicity,the genotypes and alleles of rs9582036 and rs9943922 confer susceptibility to AMD in only Han ethnicity.