OBJECTIVE: To explore the pathogenesis of two fetuses from one family affected with Joubert syndrome (JS). METHODS: Whole exome sequencing was employed to screen potential mutations in both fetuses. Suspected mutations were verified by Sanger sequencing. Impact of intronic mutations on DNA transcription was validated by cDNA analysis. RESULTS: Two novel TCTN1 mutations, c.342-8A>G and c.1494+1G>A, were identified in exons 2 and 12, respectively.cDNA analysis confirmed the pathogenic nature of both mutations with interference of normal splicing resulting in production of truncated proteins. CONCLUSION The genetic etiology of the family affected with JS has been identified.Above findings have enriched the mutation spectrum of TCTN1gene and facilitated understanding of the genotype-phenotype correlation of JS.
Abnormalities, Multiple ; diagnosis ; genetics ; Cerebellum ; abnormalities ; Eye Abnormalities ; diagnosis ; genetics ; Humans ; Kidney Diseases, Cystic ; diagnosis ; genetics ; Membrane Proteins ; genetics ; Mutation ; Pedigree ; Retina ; abnormalities ; Whole Exome Sequencing

Objective: To prepare a new type of phycocyanin/carboxymethyl chitosan-CD55 ligand peptide (CPC/CMC-CD55sp) nanospheres, and to study its targeted therapeutic effect on cervical cancer Caski cells. Methods: The novel CPC/CMC-CD55sp nanospheres (CPC/CMC-CD55sp) were synthesized by ionic cross-linking method, and the properties of nanospheres were observed by transmission electron microscopy (DLS) and fourier transform infrared spectroscopy (FTIR). The expression of CD55 on the surface of Caski and fibroblast (L-929) cells was detected by Western blotting and flow cytometry. The effect of nanospheres on the proliferation of Caski cells was detected by CCK-8. Flow cytometry and fluorescence microscopy were used to detect the uptake of microspheres by Caski cells; Western blotting and flow cytometry were used to detect the effect of CPC/CMC-CD55sp on expressions of apoptosis-related proteins and apoptosis rate in Caski cells; the hemolysis test was used to determine the biological safety of the drug. Results: CPC/ CMC-CD55sp was successfully prepared with good morphology and uniform diameter; and CD55 was highly expressed on the surface of Caski cells but low expressed on the surface of L-929 cells (P<0.01). CPC/CMC-CD55sp could targeted and efficiently reach Caski cells and be ingested into the cells. It exhibited weak hemolysis effect on human peripheral blood, which was in the safe range. CPC/ CMC-CD55sp displayed obvious inhibitory effect on Caski cell proliferation, and could induce cell apoptosis (P<0.05 or P<0.01). Conclusion: The new CPC/CMC-CD55sp can targeted inhibit the growth of cervical cancer Caski cells via inducing its apoptosis and has good bio-safety, which provides a new idea for the research and development of anti-tumor marine drugs.

Objective T o explore the com position characteristic of event related potential (E R P ) in dif-ferent visual acuity levels, and to provide theoretical basis for the objective assessm ent of visual acuity. Methods M onocular stim ulus w as perform ed on 16 selected subjects. T he subjects w ere required to look straight at the screen ahead and count the am ount of stim uli from different directions. T he pictures of optotype stim ulus w hich corresponding to three different visual acuity levels w ere show ed in the center of the screen. The ERP results w ere recorded separately. Results (1) The P1 am plitudes of m atch stim uli recorded under the supra-threshold visual acuity level w ere higher than that of m atch stim uli recorded under the threshold and sub-threshold visual acuity levels. T here w as no significant difference betw een the P 1 am plitudes of m atch stim uli recorded under the threshold and sub-threshold visual acuity levels. T he tendency of conflict stim uli w as sim ilar to that of m atch stim uli under three visual acuity levels. (2) In the 340-500 m s post-stim ulus range, P 300 com ponent w as found under supra-threshold and threshold visual acuity levels; no P 300 com ponent w as found in corresponding tim e w indow under sub-threshold visual acuity. T he differences of P 300 am plitudes am ong three visual acuity levels w ere statistically significant. T he am plitudes from high to low w ere the supra-threshold, threshold and sub-threshold visual acuity levels. Conclusion E R P can be a potential new m ethod for the objective assessm ent of visual acuity in forensic m edicine.

OBJECTIVETo explore the correlation between 13q33-q34 microdeletion and clinical phenotype.

METHODSRoutine chromosomal banding was performed to analyze the karyotype, while array-based comparative genomic hybridization (aCGH array) and single nucleotide polymorphism array(SNP array) were employed to investigate the genome copy number variations.

RESULTSThe karyotype of patient 1 was 46, XY, 9qh+,13qs. Patient 2 showed 46, XX, der (13). Patient 3 showed 46, XX, r(13) (p11.2q32) [43]/45, XX, 13[4]/46, XX, r(13;13) [2]/47, XX, 2r(13;13) [1]. Patient 4 did not undergo chromosome karyotyping analysis. Array analysis showed that four patients have different microdeletions in 13q33-34 region and had common features of 13q33-q34deletion including intellectual disability, facial dysmorphism, microcephaly, hypotonia, low birth weight and genital abnormality.

CONCLUSIONThe severity of phenotypes showed no correlation with the size of deletion in 13q33-q34. The lower percentage of patients with congenital heart disease suggested a complex pathogenesis of such disease. EFNB2, LIG4 and SOX1 in 13q33-34 region are promising candidates for mental retardation. LIG4 was also a likely candidate for microcephaly.

Child, Preschool ; Chromosome Banding ; methods ; Chromosome Deletion ; Chromosomes, Human, Pair 13 ; genetics ; Female ; Genetic Testing ; methods ; Humans ; Infant ; Intellectual Disability ; genetics ; Male

Objective: To investigate the community promotion feasibility of superficial needling plus club swing for post-stroke motion impairment of the shoulder joint. Methods:A total of 180 cases (duration <1.5 years) with post-stroke motion impairment of the shoulder joint were recruited from three community health centers in Changning District, 60 from each community. They were randomly allocated into an observation group (n=90) and a control group (n=90). Patients in both groups received standard internal and rehabilitation care. Patients in the observation group received additional superficial needling plus club swing. The visual analogue scale (VAS) was conducted before and 60 d after the treatment to evaluate the severity of shoulder pain. The active movement of the shoulder joint and activities of daily living (ADL) were also observed. Results:There were no between-group statistical differences before the treatment (allP>0.05). After a 60-day treatment, the shoulder pain severity, active range of motion of the shoulder joint and ADL in the observation group were significantly improved than those in the control group (allP<0.01). In addition, no adverse events were reported by participants in the observation group. Conclusion:Superficial needling plus club swing plays a positive role in improving post-stroke motion impairment of the shoulder joint. This safe, reliable and economical therapy has good patient compliance and is suitable for community promotion.

Objective T o study the effect of different attentional conditions on the event-related potential (E R P ) com ponents generated by the visual inform ation stim uli related to visual acuity, and provide a theoretical reference for clinical forensic visual objective evaluation. Methods W ith visual acuity opto-types as norm al form of visual inform ation stim uli, 15 volunteers as study subjects w ere supposed to ac-count the visual acuity optotypes under the attentional condition of visual stim uli. Furtherm ore, the sub-jects w ere required to listen to the storytelling carefully under the non-attentional condition of visual stim uli, and after the exam ination, they needed to answ er the story-related questions. A ll the E E G re-sults of tw o different attentional conditions from the subjects w ere recorded by 32 channel E R P system . Results U nder tw o attentional conditions, P 1 and P 300 com ponents w ere evoked by the visual acuity opto-types on supra-threshold and threshold visual acuity levels, w hile only P 1 com ponent w ere evoked by the visual acuity optotypes on sub-threshold levels. In the E R P w aveform s evoked by the visual acuity optotypes on supra-threshold, P 1 and P 300 am plitudes under attentional condition w ere larger than that un-der non-attentional condition. Conclusion A ttentional conditions can influence the detection of visual acuity. P 300 com ponent can be used to distinguish the visual acuity levels w ith supra-threshold and sub-threshold under non-attentional condition.

OBJECTIVE:To investigate the general regularity and characteristics of propylthiouracil (PTU)-associated small vasculitis (ASV),and to provide reference for rational drug use in the clinic. METHODS:ADR/ADE case reports of PTU-ASV published during 1990-2016 were retrieved. The data of 118 ADR cases were analyzed statistically. RESULTS:The incidence of PTU-ASV was higher in female and was highest in 18-59 age group. Drug dose of 87 patients were within 600 mg/d,and the inci-dence of PTU-ASV was the highest within 1-5 years after medication. Main clinical manifestations were renal and lung function in-jury. After drug withdrawal,59 patients received hormone therapy,and 30 patients received hormone combined immunosuppressive agent. Finally,115 patients were recovered and 3 patients died. CONCLUSIONS:In older to reduce or avoid the occurrence of ADR,it is necessary to regularly check antineutrophil cytoplasmic antibody related indexes and evaluate the symptoms of ADR.

OBJECTIVE:To excavate and evaluate the security alert signals of linezolid after marketing,and to provide refer-ence for rational drug use in clinic. METHODS:The reporting odds ratio(ROR)method was used to excavate the security alert signals from the adverse drug events(ADE)data in the OpenFDA platform of FDA during second quarter of 2004-2016. The low-er limit of 95%CI >1 was regarded as suggestive of ADE alert signal. RESULTS:A total of 6828534 reports were extracted, among which there were 7224 reports mainly induced by linezolid. Top 10 ADE reports were thrombocytopenia,drug interac-tion,thrombocytopenia,nausea,anaemia,serotonin syndrome,diarrhoea,pyrexia,drug ineffective,vomiting. After the detec-tion of top 200 ADE reports by ROR method,120 signals related to 18 system organ class(SOC)were identified. Top 5 ADE sig-nals in turn by SOC were medical examination,nervous system disorders,blood and lymphatic system disorders,metabolism and nutrition disorders,cardiac disorders. The high risk signals with clinical reference value included 42 cases of optic neuropathy (ROR=56.33),350 cases of serotonin syndrome(ROR=52.86),162 cases of lactic acidosis(ROR=18.30),31 cases of endo-carditis (ROR=15.38),566 cases of thrombocytopenia (ROR=14.29),122 cases of bone marrow failure (ROR=14.20),261 cases of panhematopenia (ROR=11.92),86 cases of disseminated intravascular coagulation (ROR=10.91),58 cases of toxic epidermal necrolysis(ROR=9.06),etc. As for ADE reports,male was slightly higher than female,and the patients in age group of ≥45 reported evidently more compared to younger age group. CONCLUSIONS:By detecting and evaluating alert signals of li-nezolid through OpenFDA platform,we could effectively lay the foundation for further research of pharmacovigilance.

Aim To explore the protective effects of lithium chloride ( LiCl ) on neurous injuries and phos-phorylation of tau protein at serine262 induced by okada-ic acid( OA) . Methods The neuroblastoma SK-N-SH cells were differentiated by all-trans-retinoic acid ( AT-RA) . The differentiated SK-N-SH cells were treated with OA to establish the Alzheimer′s disease cellular model. SK-N-SH cells′ viability and proliferation were measured by SRB test. Giemsa staining was used to observe cell morphology. The neurite length of SK-N-SH cells was measured by Image-Proplus software. Syn-aptophysin and phosphorylated tau protein at serine262 expression levels were tested by Western blot. Results The SK-N-SH cells which were treated with 10 μmol ·L-1 ATRA for 7 days displayed mature neuronal fea-tures. The synaptic length of SK-N-SH cells became longer. And the levels of serine262 phospho-tau was sig-nificantly elevated. 20~100 nmol·L-1 OA effectively inhibited the viability of differentiated SK-N-SH cells in a concentration-dependent manner and in a time-de-pendent manner. The OA treatment induced obvious synaptic atrophy in differentiated SK-N-SH cells. And the phosphorylation level of tau protein serine262 also greatly increased. The pretreatment with 10 mmol · L-1 LiCl significantly ameliorated the synaptic atrophy, the decrease of synaptophysin expression and the in-crease of tau phosphorylation at serine262 induced by OA in differentiated SK-N-SH cells. Conclusion LiCl could effectively inhibit OA-induced synaptic atro-phy in differentiated SK-N-SH cells, and it could also result in the increase of synaptophysin expression and the decrease of the phosphorylation of tau protein at serine262 .