[Clinical features and genetics studies of Finnish variant late infantile neuronal ceroid lipofuscinosis in two families].

Objective: To report clinical feature and results of genetic analysis of 3 patients from 2 families with Finnish variant late infantile neuronal ceroid lipofuscinosis. Methods: The clinical and ultrastructural features of 3 patients with progressive neurodegenerative diseases were retrospectively analyzed from October 2014 to December 2016 in Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center. The whole exon sequencing and Sanger sequencing were used to analyze the molecular genetics of the patients and their parents. Results: The probands were 11 years and 3 moths, 9 years and 1 month,10 years and 1 month old. All were normal at birth, and from 5-6 years old they began to develop "regression of cognition and motion, impaired vision". Physical examination at the first consultation: clear minded butignorant, unable to speak and understand instructions, unable to stand up and sit alone, unable to maintain postureupright. The brain magnetic resonance imaging(MRI) indicated diffuse cerebral and cerebellar atrophy, white matter damage. Blood biochemistry, lactic acid, acid-base balancewere normal. Electron microscopic examination of peripheral blood lymphocytes showed swelling of the nucleus, autophagy, intracellular massive deposits and abnormal vacuoles. Two compound heterozygous c.334C> T (p.Arg112Cys) and c.595C> T (p.Arg199Ter) mutations of CLN5 gene were identified in the two siblings, and the proband 3 was c.335G> A (p.Arg199His) homozyousmutation, which were inherited from their unaffected parents. Conclusions: The 3 cases with Finnish variant late infantileneuronal ceroid lipofuscinosises were normal at birth, cognitive and motor function was regressed at preschool age.Brain MRI showed whole brain atrophy, white matter lesions, there were no bovious difference from other neurodegenerative diseases. Blood biochemistry and pathological examination of lymphocytes had no specific changes. The pathogenic genes were CLN5,most are inherited in autosomal recessive way.

Analysis of serum microRNA expression in male workers with occupational noise-induced hearing loss.

Occupational noise-induced hearing loss (ONIHL) is a prevalent occupational disorder that impairs auditory function in workers exposed to prolonged noise. However, serum microRNA expression in ONIHL subjects has not yet been studied. We aimed to compare the serum microRNA expression profiles in male workers of ONIHL subjects and controls. MicroRNA microarray analysis revealed that four serum microRNAs were differentially expressed between controls (n=3) and ONIHL subjects (n=3). Among these microRNAs, three were upregulated (hsa-miR-3162-5p, hsa-miR-4484, hsa-miR-1229-5p) and one was downregulated (hsa-miR-4652-3p) in the ONIHL group (fold change >1.5 and Pbon value <0.05). Real time quantitative PCR was conducted for validation of the microRNA expression. Significantly increased serum levels of miR-1229-5p were found in ONIHL subjects compared to controls (n=10 for each group; P<0.05). A total of 659 (27.0%) genes were predicted as the target genes of miR-1229-5p. These genes were involved in various pathways, such as mitogen-activated protein kinase (MAPK) signaling pathway. Overexpression of miR-1229-5p dramatically inhibited the luciferase activity of 3' UTR segment of MAPK1 (P<0.01). Compared to the negative control, HEK293T cells expressing miR-1229-5p mimics showed a significant decline in mRNA levels of MAPK1 (P<0.05). This preliminary study indicated that serum miR-1229-5p was significantly elevated in ONIHL subjects. Increased miR-1229-5p may participate in the pathogenesis of ONIHL through repressing MAPK1 signaling.

[The application and influence factors of FACIT Fatigue Scale in SLE patients].

Objective: To evaluate the application and influence factors of the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue) scale in patients with systemic lupus erythematosus (SLE). Methods: SF-36 questionnaires were used to estimate the health-related quality of life (HRQOL) of SLE patients in Chinese Han population.FACIT-Fatigue scale was applied to measure fatigue.Disease activity was determined by SLE disease activity index (SLEDAI), meanwhile demographic parameters such as gender, disease duration, etc. were recorded. Results: A total of 223 patients with SLE were enrolled in the survey.FACIT-Fatigue scale was negatively correlated with SF-36 (P<0.05). FACIT-Fatigue scale of patients with SLE were correlated with education, erythrocyte sedimentation rate (ESR), C3, and SLEDAI score (P<0.05). The degree of bodily pain, the status of mental health and the amount of complement C3 were the independent factors of FACIT-Fatigue (P<0.1). Conclusion: FACIT-Fatigue scale is related to disease activity, quality of life, age and ESR in patients with SLE.There fore, reduce the disease activity and improve the quality of life of SLE patients may be helpful to reduce the fatigue of patients with SLE.

Defective eyelid leading edge cell migration in C57BL/6-corneal opacity mice with an "eye open at birth" phenotype.

Development of the eyelid requires coordination of the cellular processes involved in proliferation, cell size alteration, migration, and cell death. C57BL/6J-corneal opacity (B6-Co) mice are mutant mice generated by the administration of N-ethyl-N-nitrosourea (100 mg/kg). They exhibit the eyelids open at birth phenotype, abnormal round cell shape from tightened F-actin bundles in leading edge keratinocytes at E16.5, and gradual corneal opacity with neovessels. The tip of the leading edge in B6-Co mice did not move forward, and demonstrated a sharp peak shape without obvious directionality. Analysis of the biological characteristics of B6-Co mice demonstrated that abnormal migration of keratinocytes could affect eyelid development, but proliferation and apoptosis in B6-Co mice had no effect. Mutant gene mapping and sequence analysis demonstrated that in B6-Co mice, adenosine was inserted into the untranslated regions, between 3030 and 3031, in the mRNA 3'-terminal of Fgf10. In addition, guanine 7112 was substituted by adenine in the Mtap1B mRNA, and an A2333T mutation was identified in Mtap1B. Quantitative real-time polymerase chain reaction analysis showed that expression of the Hbegf gene was significantly down-regulated in the eyelids of B6- Co mice at E16.5, compared to B6 mice. However, the expression of Rock1, Map3k1, and Jnk1 genes did not show any significant changes. Abnormal keratinocyte migration and down-regulated expression of the Hbegf gene might be associated with impaired eyelid development in B6-Co mice.

[Influencing factors for the use of earplugs in workers exposed to noise in a city].

OBJECTIVE: To investigate the current status of hearing loss and the use of earplugs in workers exposed to noise who have been provided earplugs in a city, as well as major influencing factors for the use of earplugs. METHODS: Cluster random sampling was used to conduct a questionnaire survey in workers exposed to noise who had been provided earplugs in 15 enterprises with noise exposure in a city from June to December, 2014. RESULTS: In the workers exposed to noise who had been provided earplugs, the rate of high-frequency anomaly in both ears was 57.8%, and the workers who kept wearing earplugs only accounted for 55.4%. The results of binary logistic regression analysis showed that the protective factors for the use of earplugs included workers' own feeling of hearing condition (OR=1.704), comfort of earplugs (OR= 1.892), enterprise's inspection of the use of earplugs (OR=1.461), workers' knowledge of the function and usage of earplugs (OR=1.581), workers' understanding of the necessity of earplugs (OR=4.482), workers' initiative to search for related data (OR=4.029), the use of earplugs by colleagues (OR=5.071), and reminders from family members or friends (OR=2.678) (all P<0.05). CONCLUSION: The workers exposed to noise in this city have a high rate of abnormal hearing, and only half of the workers keep wearing earplugs during work. The use of earplugs is related to the factors including workers' own feeling of hearing condition, comfort of earplugs, workers' knowledge of protection, the enterprise' s management of hearing protection, and environmental support.

Association between rs1049673 polymorphism in CD36 and premature coronary heart disease.

Risk factors for premature coronary heart disease in China can be multiple; we investigated Chinese Han patients with premature coronary heart disease and a possible association with CD36 polymorphism at rs1049673, rs7755, and rs321159 sites. Outpatients were recruited according to chest X-ray coronary arteriography results; they were divided into two groups: early coronary artery lesions (premature coronary heart disease group, test group) and a control group. Coronary arteriography and laboratory blood examinations were conducted to analyze risk factors for coronary heart disease and CD36 polymorphisms. Seventy nine test and 56 control group patients were recruited. Compared with the control, the test groups had a significantly higher proportion of male patients, smoking, diabetes and metabolic syndromes, significantly higher levels of TG, LDL-C, ox-LDL, WBC, UA, FBG, and significantly lower levels of HDL-C. For rs1049673, rs7755, and rs321159 sites, patients with premature coronary heart disease have family genetic predisposition at high LDL-C level with GA, AA, and TT genotypes. Unconditional logistic regression analysis showed that gender, diabetes, high TG, LDL-C level and C carriers of rs1049673 significantly affected risk for premature coronary heart disease.

Over-expressing CYLD augments antitumor activity of TRAIL by inhibiting the NF-κB survival signaling in lung cancer cells.

The death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in tumor cells. But studies have demonstrated that many tumor cells were resistant to TRAIL-induced apoptosis. CYLD is recognized as a negative regulator of nuclear factor-kappa B(NF-κB) activity. To explore a correlation between CYLD expression and responsiveness to TRAIL in lung cancer cell lines, we established lung cancer cell lines that stably express CYLD. Our data provided the first evidence that increased expression of CYLD directly blocks TRAIL-induced NF-κB activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. CYLD may act as a therapeutic target of lung cancer. Targeting CYLD, in combination with TRAIL, may be a new strategy to treat lung cancer with high NF-κB activity.