Background Clinical work found that triamcinolone acetonide (TA)bleeding during vitrectomy in proliferative diabetic retinopathy (PDR),but its mechanism is not clear.Objective This study was to explore the anastalsis of TA in vitrectomy for PDR.Methods A prospective study was performed.Twelve eyes of 12 patients who received vitrectomy combined with the intraocular use of TA for PDR were in cluded in Tianjin Medical University General Hospital from 2011 to 2014 and served as TA group.Thirty-two eyes of 32 patients who underwent vitrectomy for epimacular membrane or macular hole were enrolled as control group.The vitreous specimens of 0.6 ～0.8 ml was collected during the surgery.The concentrations of urokinase plasminogen activator (u-PA),tissue plasminogen activator (t-PA) and plasminogen activator inhibitors 1 (PAI-1) in vatreous were measured by ELISA.Results The mean contents u-PA,t-PA and PAI-1 in the vatreous were 25.45,127.44 and 0.42 ng/ml respectively in the TA group,and those the mean contents in the control group were 22.94,142.37 and 0.27 ng/ml respectively,shouwing a significant difference between the TA group and the control group (Z=-2.268,P＜0.05).NO significant difference was found in vitreous t-PA and PAI-1 between TA and control groups (Z =-0.092,-1.847,both at P＞0.05).Conclusions Vitreous u-PA content is increased in PDR eyes,which is more likely to lead bleeding.Anastalsis of TA during vitrectomy for PDR may be relatived to decreasing vitreous t-PA and u-PA contents as well as increasing PAI-1 contents.

Objective:To observe the level of microparticles in the vitreous of patients with proliferative diabetic retinopathy (PDR), and preliminarily explore the role of microparticles in the pathogenesis of PDR.Methods:A case control study. From January to December 2018, 54 cases of 54 eyes of PDR patients (PDR group) and 20 cases of non-diabetic retinopathy patients (control group), who were diagnosed and treated with vitrectomy (PPV) in the Department of Ophthalmology, Tianjin Medical University General Hospital vitreous samples were included in the study. Among 54 eyes in the PDR group, there were 42, 21, and 17 eyes with vitreous hemorrhage (VH), traction retinal detachment (TRD), and previous intravitreal injection of drugs, respectively. Among the 20 eyes of the control group, idiopathic macular hole, idiopathic anterior macular membrane, vitreous macular traction syndrome, and complete lens dislocation were 6, 6, 2, and 6 eyes, respectively. The PDR group was divided into uncombined TRD group and combined TRD group according to PDR stage and whether TRD occurred, with 33 and 21 eyes, respectively. According to the presence or absence of VH, they were divided into groups with VH and without VH, with 42 eyes and 12 eyes, respectively. According to whether anti-vascular endothelial growth factor (VEGF) drugs were injected into the intravitreal cavity 3 days before PPV, they were divided into anti-VEGF drug group and no anti-VEGF drug group, with 17 eyes and 37 eyes respectively. The levels of retinal photoreceptor cells (RMP), platelets (PMP), endothelial cells (EMP) and phosphatidylserine (PS-MP) expressing on the membrane surface in the sample were detected by flow cytometry. The comparison between the two groups of samples was performed by t test, and the comparison between multiple groups of samples was performed by one-way analysis of variance or Mann-Whitney test. Results:Compared with the control group, the vitreous RMP level of the PDR group was significantly decreased, and the EMP and PMP levels were significantly increased. The differences were statistically significant ( t=-2.361, 5.064, 3.531; P=0.018, <0.001, 0.001). There was no statistically significant difference in PS-MP levels between the two groups ( t=-1.617, P=0.110). Compared with the TRD group, the levels of RMP and PMP in the vitreous of the TRD group were significantly increased, and the difference was statistically significant ( t=-2.221, -2.098; P=0.031, 0.041). The level of EMP in the vitreous body of the anti-VEGF drug group was significantly lower than that of the non-anti-VEGF drug group, however, it was still higher than the control group. The difference was statistically significant ( Z=-2.430, -2.499; P=0.015, 0.012). The level of PMP in the vitreous body of the eye without VH was significantly higher than that in the group with VH, and the difference was statistically significant ( t=-3.097, P=0.003). Conclusions:The elevated levels of EMP and PMP in the vitreous of PDR patients may be related to the damage of retinal capillaries; intravitreal injection of anti-VEGF drugs before surgery can reduce the level of EMP. VH may be related to the procoagulant effect of PMP.

Objective:To observe the morphological changes of the sylvian fissure on the transthalamic section of fetal brain at 20-32 weeks, and grade the fetal sylvian fissure development by means of a simple scoring system and explore its clinical feasibility.Methods:From September 2018 to June 2020, 487 normal single fetuses of 20-32 weeks were examined in Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University. The sylvian fissure maturation was analyzed on the transthalamic section of fetal brain at 20-32 weeks and was graded from 0 to 5: un-visualized (grade 0), shallow arc (grade 1), obtuse-angled platform (grade 2), right-angled platform (grade 3), acute-angled platform (grade 4), and closed operculum (grade 5). The pregnancy outcomes and gestational age were recorded.Statistical analysis was performed by SPSS 20.0 software using box plot, Mann-Whitney U test, Weighted Kappa coefficient. Results:Left sylvian fissuer grades were obtained in 280 fetuses and right sylvian fissure grades were obtained in 247 fetuses. The fetal sylvian fissure maturation at 20-32 weeks was graded from 0 to 5, which increased with advancing gestation. Grade 0 only appeared in 3 fetuses at 20 weeks, and 99.4% fetuses at 20 weeks had grade ≥1. Grade 1 appeared in 20-22 weeks, grade 2 in 20-25 weeks, grade 3 in 22-26 weeks, grade 4 in 25-32 weeks, and grade 5 in 27-32 weeks. Box-plot and Mann-Whitney U test showed that gestational week distribution of sylvian fissure at all grades was symmetric on both sides ( P>0.05). The Weighted Kappa coefficients were 0.857(95% CI=0.750-0.957) and 0.939 (95% CI=0.859-1.000), respectively, with strong consistency regarding inter- and intra-observer agreements. Conclusions:Fetal sylvian fissure maturation at 20-32 weeks can be evaluated by means of a simple scoring system with symmetrical grading of both sides.

Proliferative vitreoretinopathy (PVR) is a complication of ocular trauma, rhegmatogenous retinal detachment (RRD), and also a common cause of RRD repair surgery failure.Abnormal proliferation, migration and epithelial mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells play a leading role in the formation of PVR epiretinal membrane.Rapamycin is the specific inhibitor of mammalian target of rapamycin (mTOR). It selectively binds to the cell protein FKBP-12 and directly binds to the FKBP12-rapamycin domain (FRB) of FKBP rapamycin associated protein (FRAP) to inhibit mTOR activity.Rapamycin has a variety of rapalog (rapamycin analog), which inhibits cell proliferation and regulate cell cycle by inhibiting mTOR signal transduction pathway.It also plays a certain role in inhibiting RPE cell abnormal proliferation, migration and EMT in PVR, and protecting the repair of glial cells, inhibiting the inflammatory cells and preventing the vascular endothelial cell damage.In recent years, the clinical trials and drug studies have shown the important role of rapamycin in ocular diseases.In addition, the evidence on ocular administrations and drug safety of rapamycin has been gradually accumulated.This article reviewed the protective effects and safety of rapamycin on RPE cells and other cells in PVR.

Objective:To assess the significance of counting the number of caudal vertebral ossification centers (OCN) below fetal terminal conus medullaris in the screening for closed spina bifida and tethered cord syndrome (TCS).Methods:The OCN was counted in 961 normal fetuses(normal group) between 17 and 41 gestational weeks and in 140 fetuses with closed spina bifida or tethered cord syndrome(abnormal group) from Jan.2013 to Dec.2020 in Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Women and Children′s Hospital, School of Medicine, Xiamen University and Maternity and Child Health Care of Guangxi Zhuang Autonomous Region. The OCN was counted in the dorsal mid-sagittal section of fetal caudal spine.The reliability and agreement test were evaluated by intraclass correlation coefficients in another 50 normal fetuses. The OCN was compared between two groups. ROC curve and the cut-off value were constructed and calculated.Results:In normal group, the N increased with the growing of gestational age.In the subgroup of 17-20 weeks, the OCN ranged from 5 to 7 in most fetuses. In the others subgroups, the OCN was equal to or greater than 6 in 99.9% cases and more than 6 in 97.1% cases. In abnormal group, OCN was less than 7 in 93.0% fetuses and less than 6 in 82.8% cases. There were statistical differences between the two groups except for the subgroup of 17-20 gestational weeks( P<0.05). With the cut-off value of 6.5, the specificity and sensitivity were 93.0% and 94.3% respectively for predicting the presence of closed spinal dysraphism or TCS. Conclusions:OCN is a simple way to evaluate the position of conus medullaris and to screen for the skin-covered spine dysraphism or TSC. OCN is more than 6 in most normal fetuses. Further evaluation of spine is required in fetuses with N less than or equal to 6.

The emergence of regular short repetitive palindromic sequence clusters (CRISPR) and CRISPR- associated proteins 9 (Cas9) gene editing technology has greatly promoted the wide application of genetically modified pigs. Efficient single guide RNA (sgRNA) is the key to the success of gene editing using CRISPR/Cas9 technology. For large animals with a long reproductive cycle, such as pigs, it is necessary to screen out efficient sgRNA
Animals ; CRISPR-Cas Systems/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; Gene Editing ; RNA, Guide/genetics* ; Swine

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.