AIM: To evaluate the prevalence of refractive errors and ocular biometry in 3573 freshman students at Tianjin Medical University for 4 consecutive years. METHODS: In this university-based, cross-sectional study, comprising 3573 students, visual acuity (VA), slit-lamp examination, non-cycloplegic auto-refraction, and ocular biometry were recorded. RESULTS: The prevalence of myopia increased annually, from 2017 to 2020 were 93.5%, 94.5%, 95.9%, and 96.2%, respectively (P=0.03), and the prevalence of high myopia was 25.7%, 26.9%, 28.6%, and 28.6%, respectively. Males tended to have a higher percentage of total astigmatism than females, with astigmatism ≥0.75 and ≥1.0 D criteria. The percentage of with-the-rule astigmatism, against-the-rule astigmatism, and oblique astigmatism was 90.3%, 5.8%, and 3.9%, respectively, with astigmatism ≥1.00 D criteria. The mean spherical equivalent, axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), corneal radius (CR), and lens position (LP) were 4.37±2.52 D, 25.28±1.24 mm, 539.49±34.98 μm, 3.31±0.34 mm, 3.47±0.21 mm, 7.8±0.28 mm, and 5.04±0.32 mm, respectively. With diopter increase in myopia, the AL became longer, CR became steeper, ACD became deeper, LT became thinner, and LP became more posterior (all P<0.01). Females had a shorter AL, thinner CCT, smaller CR, shallower ACD, thicker lens, and more anterior LP than males (P<0.01). The 64% of high myopia had AL≥26 mm, meanwhile, 5.8% mild myopia and 21.1% moderate myopia had AL≥26 mm. With AL≥26 mm, mild and moderate myopia compared to high myopia, AL was shorter (26.51±0.46 vs 26.87±0.70 mm), CR was larger (8.10±0.3 vs 7.85±0.23 mm) and LT was thinner (3.39±0.19 vs 3.45±0.19 mm, P<0.001). CONCLUSION: The prevalence of myopia and high myopia is significantly high in freshman students. The majority of astigmatism is with-the-rule. Inconformity of refractive errors and ocular biometry existed in some students. Attention should be paid to the ocular biometry of myopia.

Damage to sperm DNA was proposed to play an important role in embryonic development. Previous studies focused on outcomes after fresh embryo transfer, whereas this study investigated the influence of sperm DNA fragmentation index (DFI) on laboratory and clinical outcomes after frozen embryo transfer (FET). This retrospective study examined 381 couples using cleavage-stage FET. Sperm used for intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF) underwent density gradient centrifugation and swim up processing. Sperm DFI had a negative correlation with sperm motility ( r = −0.640, P < 0.01), sperm concentration ( r = −0.289, P < 0.01), and fertilization rate of IVF cycles ( r = −0.247, P < 0.01). Sperm DFI examined before and after density gradient centrifugation/swim up processing was markedly decreased after processing (17.1% vs 2.4%, P < 0.01; 65 randomly picked couples). Sperm progressive motility was significantly reduced in high DFI group compared with low DFI group for both IVF and ICSI (IVF: 46.9% ± 12.4% vs 38.5% ± 12.6%, respectively; ICSI: 37.6% ± 14.1% vs 22.3% ± 17.8%, respectively; both P < 0.01). The fertilization rate was significantly lower in high (≥25%) DFI group compared with low (<25%) DFI group using IVF (73.3% ± 23.9% vs 53.2% ± 33.6%, respectively; P < 0.01) but was equivalent in high and low DFI groups using ICSI. Embryonic development and clinical outcomes after FET were equivalent for low and high DFI groups using ICSI or IVF. In this study, sperm DFI did not provide sufficient information regarding embryo development or clinical outcomes for infertile couples using FET.

Small molecule covalent drugs have proved to be desirable therapies especially on drug resistance related to point mutations. Secondary mutations of FLT3 have become the main mechanism of FLT3 inhibitors resistance which further causes the failure of treatment. Herein, a series of 4-(4-aminophenyl)-6-phenylisoxazolo [3,4-b] pyridine-3-amine covalent derivatives were synthesized and optimized to overcome the common secondary resistance mutations of FLT3. Among these derivatives, compound F15 displayed potent inhibition activities against FLT3 (IC 50 = 123 nM) and FLT3-internal tandem duplication (ITD) by 80% and 26.06%, respectively, at the concentration of 1 μM. Besides, F15 exhibited potent activity against FLT3dependent human acute myeloid leukemia (AML) cell lines MOLM-13 (IC 50 = 253 nM) and MV4-11 (IC 50 = 91 nM), as well as BaF3 cells with variety of secondary mutations. Furthermore, cellular mechanism assays indicated that F15 inhibited phosphorylation of FLT3 and its downstream signaling factors. Notably, F15 could be considered for further development as potential drug candidate to treat AML.

Aim: The clinical benefits of FLT3 inhibitors against acute myeloid leukemia (AML) have been limited by selectivity and resistance mutations. Thus, to identify FLT3 inhibitors possessing high selectivity and potency is of necessity. Methods & results: The authors used computational methods to systematically compare pocket similarity with 269 kinases. Subsequently, based on these investigations and beginning with in-house compound 10, they synthesized a series of 6-methyl-isoxazol[3,4- b]pyridine-3-amino derivatives and identified that compound 45 (IC50: 103 nM) displayed gratifying potency in human AML cell lines with FLT3-internal tandem duplications mutation as well as FLT3-internal tandem duplications-tyrosine kinase domain-transformed BaF3 cells. Conclusion: The integrated biological activity results indicated that compound 45 deserves further development for therapeutic remedies for AML.

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