[Combination with different anticholinergic eyedrops for the treatment of children myopia].

Objective: To observe the efficacy and feasibility of a new therapy using a combination of different anticholinergic eyedrops in controlling myopia progression and axial prolongation in adolescents. Methods: Between July 2013 and June 2014, a total of 150 myopia adolescents aged 6-12 years were recruited at the clinic of Tongji Hospital in Shanghai. Participants were assigned in a 1∶2∶2 ratio to placebo group (no medication), combined treatment group (0.5% racanisodamine eyedrops were used twice a day during semesters, 1% atropine eyedrops were used before sleep during vacation) and atropine group (1% atropine eyedrops were used before sleep everyday). All subjects wore glasses. Visual acuity, best corrected visual acuity, cycloplegic refraction, corneal curvature, axial length, intraocular pressure, fundus and adverse events were recorded every 6 months during follow-up for 24 months. Results: At baseline, there was no significant difference in age,equivalent spherical mirror number and axial length among the three groups (all P>0.05). At the end of the second year,the mean myopia progression (changes of spherical equivalent) was -2.34 (-2.93,-1.75) D,-0.63 (-1.00,-0.50) D and -0.25 (-0.50,-0.06) D in placebo group, combined treatment group and atropine group, respectively (P<0.001), and there was statistically significant difference between each two groups (all P<0.001). The axial length change of each group were (1.51±0.23) mm, (0.69±0.30) mm and (0.31±0.30) mm, respectively (P<0.001), and there was statistically significant difference between each two groups (all P<0.001). Conclusion: Therapy using a combination of different anticholinergic eyedrops can effectively control the progression of myopia and axial prolongation in adolescents, and increase the compliance of children and the safety of drug use.

Association of single-nucleotide polymorphisms, rs2235371 and rs2013162, in the IRF6 gene with non-syndromic cleft palate in northeast China.

The aim of this study was to determine the association between two SNPs (rs2235371 and rs2013162) in the interferon regulatory factor 6 (IRF6) gene and non-syndromic cleft palate (NSCP) in northeast China. We genotyped these two SNPs in 104 NSCP cases, as well as in 178 parents and 300 controls. Case-control and case-parent analyses were performed using χ2 tests and family-based association tests (FBAT). Results indicated that there were significant differences in both genotypic and allelic distributions between patients and controls at rs2235371 and rs2013162 in the IRF6 gene. Case-parent analysis revealed over-transmission of the C allele in rs2235371 and the A allele in rs2013162. Lastly, FBAT showed over-transmission of the CA haplotype. This study demonstrated that the two SNPs, rs2235371 and rs2013162, are strongly associated with NSCP in the northeast Chinese population.

Mutation analysis of four Chinese families with pure hereditary spastic paraplegia: pseudo- X-linked dominant inheritance and male lethality due to a novel ATL1 mutation.

We studied four Chinese families with pure hereditary spastic paraplegia (HSP) to investigate the clinical features and associated genetic mutations. Linkage analysis was performed for all families to map the disease locus onto autosomal chromosomes, and related loci involved in HSP on the X chromosome were also examined. Polymerase chain reaction (PCR) sequencing was used to detect gene mutations. To confirm the influence of a splice-site mutation on mRNA, we used reverse transcription-PCR and direct sequencing. Linkage analysis and ATL1 gene sequencing of amniocytes were performed for prenatal genetic diagnosis. One missense variant (c.1517T>A) and a splice-site mutation (c.1245+1G>A) in SPAST, and two missense variants (c.715C>T, c.1204T>G) in ATL1 were identified. The c.1245+1G>A mutation caused a deletion of exon 9 in the SPAST gene. Prenatal genetic diagnosis showed that fetus did not carry the ALT1 c.1204T>G mutation. Follow-up was maintained for 5 years, and the negative result was confirmed by evidence of a healthy growing boy. We identified two novel mutations and two previously reported mutations in SPAST and ATL1, respectively. The family with the ATL1 c.1204T>G mutation exhibited male-lethality, female infancy-onset, and pseudo- X-linked dominant transmission, which had never been previously reported for HSP. Characteristic facial features were also noticed. The boy on whom prenatal gene diagnosis was performed is healthy and without unusual facies, suggesting that the c.1204T>G mutation might be related to these features. The results extend the genetic spectrum of HSP and suggest that linkage analysis remains a powerful tool in gene discovery studies.

Variations in WNT3 gene are associated with incidence of non-syndromic cleft lip with or without cleft palate in a northeast Chinese population.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect. Several WNT genes are involved in craniofacial embryogenesis, and therefore may play an important role in the etiology of NSCL/P. Two SNPs (rs3809857 and rs9890413) in the WNT3 gene were subjected to case-control and case-parent analysis by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 236 unrelated patients with NSCL/P, including 128 elementary families (185 mothers and 154 fathers), and 400 control individuals from northeast China. The rs3809857 SNP, under the assumption of a dominant model, was found to induce a 2-fold lower risk of NSCL/P ORGG vs GT + TT = 0.605, 95%CI = 0.436-0.839, P = 0.003). Moreover, the family-based association test revealed an under-transmission for the minor allele T. On the other hand, we observed a significant association in the case-control and case-parent analysis of the SNP rs9890413. In addition, the P values for the haplotype of rs3809857-rs9890413 were observed to be statistically significant (P = 0.004). In conclusion, our study confirmed the association between the WNT3 variant and NSCL/P in the population tested.

A novel mutation of the MFN2 gene in a Chinese family with Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (CMT) is a group of clinically and genetically heterogeneous inherited neuromuscular disorders. At present, more than 30 loci have been reported to be associated with CMT disease; point mutations in the mitofusin 2 (MFN2) gene is one of the most common causes. We studied a Chinese family with CMT disease in which the phenotype of affected individuals varied, and the weakness condition of the distal legs in males, except the proband, was less severe than in females in this family. Linkage analysis and PCR sequencing revealed a missense mutation (NM_014874.3:c.1066 A>G) in the MFN2 gene, resulting in an animo acid substitution of threonine to alanine in condon 356 (Thr356Ala). This is a novel phenotype and mutation for CMT family.

Experimental investigation of the mammary gland tumour phantom for multifrequency microwave radio-thermometers.

Microwave radiometry is a spectral measurement technique for resolving the electromagnetic radiation of matter when its temperature is above absolute zero. The radio-thermometer utilises this technique and consequently can provide temperature distributions in subcutaneous biological tissues. A new phantom was proposed that imitates a mammary gland tumour, and the brightness temperature was observed using radio-thermometers operated at different frequencies, 1.75GHz and 3GHz. The proposed phantom, simulating heat diffusion propagated by tissues around real tumours, revealed that the thermal characteristics of the tumour imitator were well matched to the heat transfer properties of a real tumour and a proportional linear relationship between the location of the tumour imitator and the brightness temperature in a homogenous medium was established. From experiments using the proposed mammary gland tumour phantom and a clinical trial on patients with breast cancer, it could be concluded that a radio-thermometer with a short wavelength (lambda = 10cm, i.e. f= 3GHz) is useful to resolve a thermal anomaly at a shallow depth in an homogenous medium such as a breast.

Resonant optical nonlinearity measurement of Yb(3+) / Al(3+) codoped optical fibers by use of a long-period fiber grating pair.

A new method of measuring optical nonlinearity for resonant nonlinear optical fibers is proposed. A long-period fiber grating (LPG) pair was used to measure the nonlinear refractive index n(2) of a Yb(3+)/Al (3+) codoped optical fiber, which was spliced between the two LPGs, as the fiber was pumped with a laser diode. The nonlinear refractive index of the Yb(3+)/Al (3+) codoped fiber near 1580 nm depended on the pump power. As the pump power increased, the nonlinear refractive index decreased. At launched pump powers of 2-8 mW, the nonlinear refractive index of the Yb(3+)/Al (3+) codoped fiber near 1580 nm was ~7.5x10(-15)m (2)/W .

Observation and analysis of residual stress development resulting from OH impurity in optical fibers.

We report experimental results on the development of residual stress due to OH impurity in optical fibers. The effect of OH impurity on residual stress is demonstrated by direct residual stress measurement. The residual stress at the outer-cladding/jacketing-tube boundary of the fiber drawn at 3.48 N was found to be -61 MPa . The residual compressive stress is attributed to the viscosity decrease induced by a significant OH impurity at the boundary, as measured by a Fourier transform infrared microscope.

Residual stress relaxation in the core of optical fiber by CO(2) laser irradiation.

We observed residual stress relaxation by CO(2) laser irradiation in the cores of optical fibers by direct stress measurement. It was demonstrated that the mechanical stress was fully relaxed by CO(2) laser irradiation and that the remaining stress in the core was thermal stress that was due to a mismatch of the thermal expansion coefficients of the fiber core and cladding. The net core stresses after relaxation were 17, 68, and 203 MPa in Ge-B-codoped fibers drawn at 0.53, 1.38, and 3.48 N, respectively. Changes in the refractive indices of the cores as a result of residual stress relaxation were also estimated.

Azetidin-2-one derivatives as inhibitors of thrombin.

A series of 3-(3-guanidinopropyl)-azetidin-2-one derivatives was prepared and evaluated as inhibitors of cleavage of synthetic substrates in vitro by the serine proteases thrombin, trypsin and plasmin. The N-unsubstituted, 4-phenethyl derivative 9a demonstrated weak inhibition of these enzymes but acetylation of the beta-lactam N atom afforded 9b, an effective, time-dependent inhibitor of thrombin and a potent inhibitor of plasmin. Variation of the 4-position of the beta-lactam ring was examined in conjunction with different N-substituents to provide a series of potent, time-dependent inhibitors of thrombin. A C-4 substituent was essential for good inhibitory properties and, in general, polar C-4 substituents enhanced the selectivity of inhibition for thrombin compared to plasmin. A trans relationship between the C-4 and C-3 substituents was found to be superior to a cis disposition whilst homologation of the guanidinopropyl side chain to that of a guanidinobutyl moiety reduced activity. Several compounds were effective inhibitors of thrombin-induced clot formation in human plasma in vitro but activity in this assay did not correlate well with inhibition of thrombin-induced cleavage of a synthetic substrate, presumably a consequence of inherent chemical instability and degradation in plasma.

Active site-directed thrombin inhibitors--II. Studies related to arginine/guanidine bioisosteres.

A series of N-arylsulfonylarginine amides was synthesized wherein the guanidine or arginine moiety was isosterically replaced by a number of heterocyclic functionalities. These compounds were evaluated as potential active-site inhibitors of thrombin. Bisamidines 11a-n showed a similar SAR to that of simple arginine compounds. The ex vivo clotting time measurement of 11d after ip dosing showed prolongation of clotting time in rats.