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

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

BACKGROUND: Although some studies have been done on the functional change of cochlea in chickens during prolonged administration of kanamycin,few studies on ultrastructural changes in chicken cochlea have been reported.OBJECTIVE: To observe ultrastructural changes of the chicken basilar papilla following poisoning with prolonged administration of kanamycin.DESIGN: A completely randomized design and controlled observation.SETTING: Affiliated Xinhua Hospital, Shanghai Second Medical University.MATERIALS:The experiment was conducted in Xinhua Hospital Affiliated to Medical College, Shanghai Jiao Tong University from June 2001 to August 2003. Newly born Roman chickens (n=78), of either sex, provided by Shanghai Guixing Breeding Chick Farm, were used as subjects.METHODS: 200 mg/kg kanamycin was injected into muscles daily at day 3 after birth for 10 days. Then they were divided into 3 groups randomly:①typical application group: The chickens were applied with drugs no longer, and then killed at days 1, 3,7, 10 and 15, 6 chickens in each time phase. ②prolonged application group: 200 mg/kg kanamycin per day were injected into muscles continuously, and then killed at days 13, 17, 20, 25and 30, 6 chickens in each time phase. ③control group: The chickens were not treated with any drug. They were assigned into 3, 13 and 33 days groups with 6 chickens in each time phase. When the chickens were killed they were at the same age with the experime ntal animals at days 0, 10 and 30 of kanamycin treatment. All the experimental animals were studied with auditory brain-stem response (ABR) and scanning electron microscopy in chicken basilar papilla to observe ultrastructural change of cochlea, threshold, latency and amplitude of ABR wave I.MAIN OUTCOME MEASURES: ①Ultrastructural change of the chicken basilar papilla, and ② ABR result of chicken.RESULTS: A total of 78 Roman chickens were involved in the result analysis, without dropout. ①Outcome of ABR: Loss and recovery of chicken ABR threshold value was similar between within continuous administration for 20 days and administration for 10 days plus 10 days of recovery (drug withdrawal group). Twenty days after administration, ABR threshold significantly increased again. ②Outcome of scanning electron microscopy: At the end of 10-day kanamycin administration, hair cells in 40％ proximal chicken basilar papilla were destroyedand disappeared completely. Although continuous administration was performed, the hair cells began to regenerate and repair after damage. Within the 20-day continuous administration, the regenerated hair cells of basilar papilla developed maturity, which was mostly coincident with the administration for 10 days group. At day 25, regenerated hair cells of proximal basilar papilla were injured once again. At day 30, most of the regenerated hair cells were destroyed and disappeared.CONCLUSION: Prolonged administration of kanamycin obviously prevents the full repair of chicken basilar papilla damaged by kanamycin poisoning.

Objectives To explore the brain white matter integrity among the patients with buprenorphine tables,scopolamine and promethazine solution(BSP) dependence after abstinence.Methods BSP-dependent patients( n=16)and age/eduction-matched healthy control subjects ( n=18) were assessed by diffusion tensor imaging (DTI) after 3 days,1 month and 2 months of abstinence.White matter (WM) integrity was measured with DTI as fractional anisotropy ( FA),an index of intravoxel orientational coherence of white matter fibers.Results Compared with health controls,FA values were significantly lower in frontal,parietal,temporal and corpus callosum in the BSP addicts after 3-day withdrawal (P＜0.001,uncorrected).Increased FA values in left superior frontal cortex,right medial frontal gyms and fight inferior parietal gyrus were found in BSP users after 2 months of abstinence (P ＜0.001,uncorrected).However,no significant difference was found between these BSP addicts after 1-month abstince.Compared with health controls,BSP dependent subjects still exhibited significantly lower FA in the corpus callosum,frontal,parietal and temporal WM after 2-month withdrawal (P ＜ 0.001,uncorrected ).Conclusion The abnormalities showed less recovery in BSP dependent individuals with abstinence in white matter that suggests that rehabilitation time should be further prolonged for BSP addicts and emphasis cognitive-behavioral therapy to assist BSP abusers rebuild social functions.

Objective To investigate the expression of FRAT1 and β-catenin in human brain glioma,analyze the correlation between the expression and clinical pathological grades and the correlation of the two genes.Methods FRAT1 and β-catenin were detected by immunohistochemistry in 84 human brain glioma tissues and 6 human normal brain tissues.Results 66.7 ％ (56/84) and 77.4 ％ (65/84) of human brain glioma tissues expressed FRAT1 and β-catenin protein,whereas no FRAT1 and β-catenin protein expression was detected in human normal brain tissues.The expression levels of FRAT1 and ββ-catenin increased markedly with the ascending of pathologic grade of tumor specimens (r =0.55,P ＜ 0.01,r =0.70,P ＜ 0.01),there was a positive correlation between FRAT1 and β-catenin (r =0.77,P ＜ 0.01).Conclusion FRAT1 and β-catenin over-expression maybe closely related with occurrence and development of human brain gliomas.The results provide important supplements for the research of Wnt/β-catenin pathway.Meanwhile,FRAT1 may act as a valuable biomarker for molecular diagnosis of glioma and a potential target for gene therapy of glioma.