Study on the role of MYCN in retinoblastoma by inhibiting p53 and activating wnt/ßcatenin/Fra-1 signaling pathway by reducing DKK3.

Retinoblastoma (RB) is a pediatric malignancy, typically diagnosed at birth or during early childhood. The pathogenesis of RB is marked by the amplification of the Basic Helix-Loop-Helix (BHLH) Transcription Factor MYCN, which serves as a transcriptional regulator capable of binding to Dickkopf 3 (DKK3). However, the precise role of DKK3 in the malignant progression of RB cells caused by MYCN remains elusive. In the present study, the expression of MYCN was either overexpressed or interfered in RB cells. Subsequently, the expression level of DKK3 was assessed through quantitative real-time polymerase chain reaction and western blot analysis. Cell proliferation was evaluated using the Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine staining, while cell cycle progression and apoptosis were analyzed by flow cytometry and western blot analysis, respectively. Additionally, the expression of proteins involved in the Wnt/ß-catenin/Fra-1/p53 signaling pathway was evaluated via western blot analysis. To gain further insights, Wnt agonists and the P53 inhibitor PFT-α were introduced into exploration. The current investigation revealed a negative correlation between the expression levels of MYCN and DKK3 in RB cells. Additionally, DKK3 overexpression inhibited cell proliferation, promoted cell apoptosis, and arrested cell cycle in RB cells with high expression of MYCN. Moreover, enhanced DKK3 expression inhibited proliferation, promoted cell cycle arrest and apoptosis of RB cells by modulating the wnt/ßcatenin/Fra-1/p53 signaling pathway. Furthermore, in vivo experiments revealed that overexpression of DKK3 inhibits the growth of RB tumors. Collectively, our findings elucidate that MYCN stimulates the Wnt/ß-catenin/Fra-1 pathway by suppressing DKK3 expression, ultimately suppressing p53 activity and contributing to malignant progression of RB.

Characterizing atom clouds using a charge-coupled device for atom-interferometry-based G measurements.

Precise information of positions and sizes of atom clouds is required for atom-interferometry-based G measurements. In this work, characterizing atom clouds using a charge-coupled device (CCD) is presented. The parameters of atom clouds are extracted from fluorescence images captured by the CCD. For characterization, in-situ calibration of the magnification of the imaging system is implemented using the free-fall distance of atom clouds as the dimension reference. Moreover, influence of the probe beam on measuring the positions of atom clouds is investigated, and a differential measurement by reversing the direction of the probe beam is proposed to suppress the influence. Finally, precision at sub-mm level for characterizing atom clouds is achieved.

Multivariate analysis of the effect of Chalazia on astigmatism in children.

BACKGROUND: Chalazion may affect visual acuity. This study aimed to evaluate refractive status of chalazia and effect of different sites, sizes, and numbers of chalazion on astigmatism. METHODS: Three hundred ninety-eight patients aged 0.5-6 years were divided into the chalazion group (491 eyes) and the control group (305 eyes). Chalazia were classified according to the site, size, and number. Refractive status was analyzed through the comparison of incidence, type, mean value and vector analysis. RESULTS: The incidence, type, refractive mean and of astigmatism in the chalazion group were higher than those in the control group, and the difference was statistically significant (P < 0.05). For comparison of the incidence, the middle-upper eyelid (50%) was highest, followed by 41.77% in the medial-upper eyelid, both higher than that in the control group (P < 0.05). In medium (54.55%) and large groups (54.76%) were higher than that in the control group (27.21%) (P < 0.05). In multiple chalazia, the astigmatism incidence for chalazion with two masses was highest (56%), much higher than that in the control group (P < 0.05). However, this difference was not significant in chalazion with ≥3 masses (P > 0.05). For comparison of the refractive mean,the medial-upper eyelid, middle-upper eyelid and medial-lower eyelid were higher than the control group (P < 0.05) (P < 0.05). The 3-5 mm and >5 mm group were higher than those in the control group and <3 mm group(P < 0.05), and the>5 mm group was larger than the 3-5 mm group，suggesting that the risk of astigmatism was higher when the size of masses > 5 mm. Astigmatism vector analysis can intuitively show the differences between groups, the results are the same as refractive astigmatism. CONCLUSION: Chalazia in children can easily lead to astigmatism, especially AR and OBL. Chalazia in the middle-upper eyelid, size ≥3 mm, and multiple chalazia (especially two masses) are risk factors of astigmatism. Invasive treatment should be performed promptly if conservative treatment cannot avoid further harm to the visual acuity due to astigmatism.

Effect of the BOPPPS model combined with case-based learning versus lecture-based learning on ophthalmology education for five-year paediatric undergraduates in Southwest China.

BACKGROUND: To investigate the effect of the bridge-in, objective, preassessment, participatory learning, post assessment, and summary (BOPPPS) model combined with case-based learning (CBL) on ophthalmology teaching for five-year paediatric undergraduates. METHODS: The effects of the BOPPPS model combined with CBL (BOPPPS-CBL) and traditional lecture-based learning (LBL) on ophthalmology teaching were compared among students in a five-year programme. The questionnaire surveys of the students were collected and statistically analysed after the class. The final examination scores, including on elementary knowledge and case analysis, in the two groups were analysed. RESULTS: There were no statistically significant differences between the teachers and students in the baseline data. More students agreed that the BOPPPS-CBL model helped develop their problem-solving skills, analytical skills and motivation for learning better than the LBL model. There was no significant difference in learning pressure between the two groups. The final examination scores of the BOPPPS-CBL group were significantly higher than those of the LBL group. The overall course satisfaction of the BOPPPS-CBL group was obviously higher than that of the LBL group. CONCLUSIONS: The BOPPPS-CBL model is an effective ophthalmology teaching method for five-year paediatric undergraduates.

Severe ophthalmia neonatorum in Southwest China: a 5-year review of demographics, microbiological results, and risk factors.

PURPOSE: To evaluate the microbiological characteristics and risk factors of severe ophthalmia neonatorum (ON) in Southwest China. METHODS: In this retrospective review, data on demography, microbiological results, and risk factors were analyzed. Data were obtained from medical records of patients with severe ON treated at Children's Hospital of Chongqing Medical University from January 2015 to December 2019. To understand the risk factors for severe ON, maternal and neonatal factors were compared between the severe and non-severe ON groups. RESULTS: A total of 1397 neonates with ON were included, of whom 12% (n = 172) had severe ON, and 88% (n = 1225) had non-severe ON. Microbial detection and drug susceptibility tests were performed on 169 patients with severe ON. Culture results were positive for 76 patients, with gram-positive bacteria in 71.1% (n = 54), gram-negative bacteria in 25.0% (n = 19), and multiple microorganisms in 3.9% (n = 3) neonates. The most commonly detected organisms were Staphylococcus aureus (29%) and Staph. epidermis (27%), followed by Escherichia coli (8%). Neisseria gonorrhea (8%), Moraxella catarrhal (5%), Streptococcus pneumoniae (4%), Haemophilus influenza (4%), and Chlamydia trachomatis (1%). The main risk factors for severe ON were obstruction of the nasolacrimal duct (χ2 = 10.794, P = 0.001), meconium aspiration syndrome (χ2 = 6.252, P = 0.012), and cesarian section (χ2 = 5.118, P = 0.024). Neonatal ocular prophylaxis was a protective factor for severe conjunctivitis (χ2 = 6.905, P = 0.009). CONCLUSIONS: Staphylococcus is the most common pathogen of severe ON. Nasolacrimal duct obstruction (NLDO) is a risk factor for ON.

Thygeson's superficial punctate keratitis (TSPK): a paediatric case report and review of the literature.

BACKGROUND: Thygeson's superficial punctate keratitis (TSPK) is reportedly a rare disease with an insidious onset, numerous remissions and exacerbations, and a long duration. The corneal lesions are elevated, whitish-grey in colour, and granular in the intraepithelium. A few reported cases of TSPK exist, and paediatric experience is limited. Due to the unknown aetiology and controversial treatment strategies for TSPK, we performed a literature review to summarize the criteria for the diagnosis, treatment and prognosis of TSPK to provide a basis for the treatment of TSPK in paediatric patients. CASE PRESENTATION: The clinical course of a boy with TSPK who repeatedly presented with episodes of tearing, photophobia and foreign body sensation in both eyes is described. Irritation was uncontrollable with antiviral and antibiotic medications, and it was managed by corticosteroids. No recurrence was reported at the 1-year follow-up after corticosteroid replacement and tapering. CONCLUSIONS: The clinical features, treatment and prognosis between adult and paediatric TSPK patients have many similarities. The diagnosis of TSPK in children is more difficult, leading to missed diagnosis. TSPK needs to be carefully differentiated from other types of keratitis, especially intraepithelial secondary and other infectious ocular surface diseases.

Edaravone prevents high glucose-induced injury in retinal Müller cells through thioredoxin1 and the PGC-1α/NRF1/TFAM pathway.

CONTEXT: Oxidative injury in a high-glucose (HG) environment may be a mechanism of diabetic retinopathy (DR) and edaravone can protect retinal ganglion cells by scavenging ROS. OBJECTIVE: To explore the effect of edaravone on HG-induced injury. MATERIALS AND METHODS: First, Müller cells were cultured by different concentrations of glucose for different durations to obtain a suitable culture concentrations and duration. Müller cells were then divided into Control, HG + Vehicle, HG + Eda-5 µM, HG + Eda-10 µM, HG + Eda-20 µM, and HG + Eda-40 µM groups. Cells were cultured by 20 mM glucose and different concentrations of edaravone for 72 h. RESULTS: The IC50 of glucose at 12-72 h is 489.3, 103.5, 27.92 and 20.71 mM, respectively. When Müller cells were cultured in 20 mM glucose for 72 h, the cell viability was 52.3%. Edaravone significantly increased cell viability compared to Vehicle (68.4% vs 53.3%; 78.6% vs 53.3%). The EC50 of edaravone is 34.38 µM. HG induced high apoptosis rate (25.5%), while edaravone (20 and 40 µM) reduced it to 12.5% and 6.89%. HG increased the DCF fluorescence signal (189% of Control) and decreased the mitochondrial membrane potential by 57%. Edaravone significantly decreased the DCF fluorescence signal (144% and 132% of Control) and recovered the mitochondrial membrane potential to 68% and 89% of Control. Furthermore, HG decreased the expression of TRX1, PGC-1α, NRF1 and TFAM, which were restored by edaravone. DISCUSSION AND CONCLUSION: These findings provide a new potential approach for the treatment of DR and indicated new molecular targets in the prevention of DR.

Influence of Vitamin A deficiency on the transcriptomic profile of rat meibomian glands.

PURPOSE: Vitamin A deficiency (VAD) is associated with chalazion in young children. However, the underlying molecular mechanism remains unclear. In the present study, transcriptome data from rat meibomian glands (MGs) were analyzed to reveal specific molecular responses to VAD. METHODS: Total RNA was extracted and purified for library preparation and transcriptome sequencing. Differentially expressed genes (DEGs) between vitamin A normal (VAN) and VAD rats were analyzed using DESeq software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were performed using the GO seq R package and KOBAS software. Real-time quantitative reverse transcription polymerase chain reaction was used to validate the RNA sequencing results. RESULTS: The number of DEGs in the VAD group compared to the VAN group was 3129 (1531 upregulated and 1598 downregulated) in the rat MGs. VAD upregulated a large number of lipid metabolism-related genes. GO analysis showed that the most enriched and meaningful terms were related to lipid metabolism (e.g., "oxidation-reduction process, GO: 0,055,114," "lipid metabolic process, GO: 000,662"). KEGG pathway analysis showed that most of the enriched signaling pathways were involved in lipid metabolism, including the PPAR signaling pathway associated with retinoic acid (RA)-mediated nuclear receptors. CONCLUSION: These findings demonstrate that VAD regulates the expression of numerous genes in the rat MG and that many of these genes are involved in lipid metabolic pathways.

Association between allergic conjunctivitis and provisional tic disorder in children.

BACKGROUND: Allergic diseases are associated with a higher risk of Tourette's syndrome (TS). Provisional tic disorder (PTD) and eye blinking are often reported as the initial symptoms both in TS and in allergic conjunctivitis (AC). OBJECTIVE: To investigate the association between AC and PTD in children of 4-10 years of age in southwest China. METHODS: This case-control study was carried out at the Children's Hospital of Chongqing Medical University between January 2016 and June 2017. Age- and gender-matched children without PTD were included as the control group. Intraocular pressure was measured by non-contact tonometry, tear film break-up time by slit-lamp examination, and allergens by skin prick test (SPT). Multivariable logistic regression analysis was applied to adjust for the simultaneous effects of AC, dry eye, and allergic history in children with PTD. RESULTS: The frequency of AC was higher in the PTD group (74.3%, 52/70) than in the control group (17.1%, 12/70) (P < 0.001). The frequencies of positive SPT were found to be higher in the PTD group (80.0%, 56/70) than in the control group (20.0%, 14/70). AC, dry eye, and history of allergic rhinitis were significantly associated with PTD. CONCLUSION: The frequencies of AC are high in children with PTD. AC and dry eye may be both associated with PTD in children.

Lacrimal passage irrigation in children with Stevens-Johnson syndrome or toxic epidermal necrolysis: a five-year retrospective study.

BACKGROUND: To identity the effect of lacrimal system irrigation in the acute stage in children with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). METHODS: A retrospective review of 39 patients with SJS or TEN from 2012 to 2017 was analyzed. Patients were divided into two subgroups according to whether they received irrigation in the acute stage. The irrigation group included 21 inpatients and the control group included 18 inpatients. The χ2 test was used to compare clinical findings and data in both groups. RESULTS: The rate of lacrimal system obstructions in the chronic stage of SJS or TEN in the irrigation group was significantly lower than in the control group (p < 0.01). A significant difference was also found between the epiphora rates in patients with SJS or TEN in the chronic stage in the two groups (p = 0.047). One of 15 patients with mild dry eyes or without dry eyes in the irrigation group had epiphora, and it affected five of 12 in the control group. The difference between the two groups was significant (p = 0.03). Epiphora in the two patients in the control group was long-term, owing to the disappearance of puncta marks. CONCLUSIONS: Lacrimal system irrigation with dexamethasone drops in the acute stage was a simple way to lessen lacrimal system obstructions and epiphora in patients with SJS or TEN. It should be considered a conventional ocular treatment for SJS or TEN.

Incidence of retinopathy of prematurity in southwestern China and analysis of risk factors.

BACKGROUND: The aim of this study was to screen for retinopathy of prematurity (ROP) in southwestern China and understand the prevalence and risk factors of ROP, which may provide evidence useful in the prevention and treatment of ROP. MATERIAL/METHODS: 1864 preterm infants (gestational age of <37 weeks and birth weight of ≤2500 g) underwent ROP screening from January 2009 to November 2012 in Southwest China. The medical information of infants during perinatal period was reviewed, and risk factors of ROP were determined. A total of 1614 infants were recruited for final analysis. RESULTS: Incidence of ROP was 12.8%. The first, second, third, and fourth stage of ROP was found in 64.6%, 29.6%, 3.4%, and 0.5% of infants, respectively. No fifth stage of ROP was observed. In addition, 7.7% of infants required surgical intervention. In our Department of Neonatology, the incidence of ROP was 20.0%, which was significantly higher than in non-hospitalized patients (9.9%). The incidence of ROP remained unchanged over the years. Independent risk factors of ROP included low birth weight (p=0.049), low gestational age (p=0.008), days of oxygen supplementation (p=0.008), and myocardial injury after birth (p=0.001). CONCLUSIONS: The prevalence of ROP in preterm infants is relatively high in Southwest China, and low birth weight, low gestational age, days of oxygen supplementation, and myocardial injury after birth are independent risk factors for ROP.

Flipped Classroom Based on Outcomes-Based Education Improves Student Engagement and Clinical Analysis Competence in Undergraduates Ophthalmology Clerkship.

Objective: To investigate the effectiveness of flipped classrooms (FC) based on outcomes-based education (OBE) on clinical ophthalmology clerkships. Methods: Ninety-nine undergraduates were non-randomly assigned to the FC based on the OBE (FC-OBE) group or traditional lecture (TL) group in the ophthalmology clerkship. Pre- and post-tests were performed to assess student learning outcomes. Anonymous questionnaires were collected to compare students' attitudes and classroom engagements between the two groups. Results: More participants agreed FC-OBE was helpful in developing teamwork ability and knowing the work standard. Teaching staff in the FC-OBE classroom received higher evaluations. More participants in the FC-OBE group had higher classroom engagement in skills and emotions than in the TL group. The post-class test scores, mainly case analysis scores were higher in the FC-OBE group than in the TL group. Conclusion: FC-OBE classroom improves student engagement and clinical analysis competence in undergraduate ophthalmology clerkship.

Decrease in retinal neuronal cells in streptozotocin-induced diabetic mice.

PURPOSE: Little is known about retinal neuronal loss in the retinas of diabetic mice. The purpose of this study was the quantitative assessment of retinal neural cell number in diabetic mice. METHODS: Five-week-old C57BL/6 mice were used as a diabetic model with streptozotocin. Mice were studied over the course of 6 and 12 weeks after the onset of diabetes. Intraocular pressure (IOP) was measured with a noninvasive TonoLab tonometer. The retinal ganglion cells (RGCs) were counted at two different time points after the induction of diabetes and examined using the immunofluorescence technique and quantitative analysis. RESULTS: The diabetic mice had significantly elevated IOP levels at 6 and 12 weeks after the onset of diabetes compared with the age-matched control mice (p<0.01 and p<0.001, respectively). The temporal course of Brn3a+ RGC and Neuronal Nuclei+RGC (NeuN+ RGC) loss induced by intraperitoneal injection of streptozotocin followed a similar trend. At 6 and 12 weeks after the onset of diabetes, the number of Brn3a+ RGCs (p<0.05 at 6 weeks; p<0.001 at 12 weeks) and NeuN+ RGCs (p<0.05 at 6 weeks; p<0.001 at 12 weeks) was significantly lower in diabetic mice than age-matched control mice. In the retinal flatmounts, the number of Brn3a+ RGCs (p<0.05 at 6 weeks, p<0.01 at 12 weeks) was also significantly lower in diabetic mice than control mice. The IOP in diabetic mice was negatively related with RGCs in cross sections. The cut-off value of IOP was 14.2 mmHg for diabetes. CONCLUSIONS: This is a specific quantitative study of neural cell loss in the retina during diabetes. These data suggest that retinal neural cell reduction occurs in diabetic mice. It indicates that RGC loss may be an important component of diabetic retinopathy.

Downregulation of miR-211-5p Promotes Carboplatin Resistance in Human Retinoblastoma Y79 Cells by Affecting the GDNF-LIF Interaction.

Purpose: To investigate the role of the miR-211-5p-GDNF signaling pathway in carboplatin resistance of retinoblastoma Y79 cells and what factors it may be affected by. Methods: A carboplatin-resistant retinoblastoma cell line (Y79R) was established in vitro. RNA-seq and microRNA-seq were constructed between Y79 and Y79R cells. RNA interference, RT-PCR, Western blot (WB), and flow cytometry were used to verify the expression of genes and proteins between the two cell lines. The TargetScan database was used to predict the microRNAs that regulate the target genes. STING sites and Co-Immunoprecipitation (COIP) were used to study protein-protein interactions. Results: GDNF was speculated to be the top changed gene in the drug resistance in Y79R cell lines. Moreover, the speculation was verified by subsequent RT-PCR and WB results. When the expression of GDNF was knocked down, the IC50 of the Y79R cell line significantly reduced. GDNF was found to be the target gene of miR-211-5p. Downregulation of miR-211-5p promotes carboplatin resistance in human retinoblastoma Y79 cells. MiR-211-5p can regulate the expression of GDNF. Our further research also found that GDNF can bind to LIF which is also a secreted protein. Conclusion: Our results suggest that downregulation of miR-211-5p promotes carboplatin resistance in human retinoblastoma Y79 cells, and this process can be affected by GDNF-LIF interaction. These results can provide evidence for the reversal of drug resistance of RB.

Refractive status and optical components in premature infants with and without retinopathy of prematurity: A 4- to 5-year cohort study.

This study was aimed to investigate the characteristics of refractive parameters in premature infants and children aged 3-8 years with mild retinopathy of prematurity (ROP) and to explore the effects of premature delivery and mild ROP on the development of refractive status and ocular optical components. Premature infants who underwent ocular fundus oculi screening in our hospital between January 2009 and February 2011 were included and divided into the ROP group and the non-ROP group. Full-term infants were the controls. The results of the annual ocular examination conducted between 2014 and 2018 were analysed, and the refractive status, optical components, and developmental trends were compared among the three groups. The total follow-up time was 4-5 years. The prevalence of myopia and astigmatism was high in the ROP group (P < 0.05). In the non-ROP group, the prevalence of myopia was also higher than that in the control group. The prevalence of myopia increased with age in the ROP and non-ROP groups, while the prevalence of astigmatism remained unchanged. In the ROP group, the corneal refractive power was the largest, the lens was the thickest and the ocular axis was the shortest; in the control group, the corneal refractive power was the smallest, the lens was the thinnest, and the ocular axis was the longest. These parameters in the non-ROP group were between those in the two groups mentioned above (P < 0.05). The corneal refractive power was relatively stable at 3-8 years old in the three groups. The change in lens thickness was small in both the ROP group and the non-ROP group (P = 0.75, P = 0.06), and the lens became thinner in the control group (P < 0.001). The length of the ocular axis increased in the three groups. Preterm infants are more likely to develop myopia than full-term infants, and children with ROP are more likely to develop both myopia and astigmatism. Thicker lenses were the main cause of the high prevalence of myopia in premature infants with or without ROP.

IL-17B/IL-17RB signaling cascade contributes to self-renewal and tumorigenesis of cancer stem cells by regulating Beclin-1 ubiquitination.

Cancer stem cells (CSCs) are characterized by robust self-renewal and tumorigenesis and are responsible for metastasis, drug resistance, and angiogenesis. However, the molecular mechanisms for the regulation of CSC homeostasis are incompletely understood. This study demonstrated that the interleukin-17 (IL-17)B/IL-17RB signaling cascade promotes the self-renewal and tumorigenesis of CSCs by inducing Beclin-1 ubiquitination. We found that IL-17RB expression was significantly upregulated in spheroid cells and Lgr5-positive cells from the same tumor tissues of patients with gastric cancer (GC), which was closely correlated with the degree of cancer cell differentiation. Recombinant IL-17B (rIL-17B) promoted the sphere-formation ability of CSCs in vitro and enhanced tumor growth and metastasis in vivo. Interestingly, IL-17B induced autophagosome formation and cleavage-mediated transformation of LC3 in CSCs and 293T cells. Furthermore, inhibition of autophagy activation by ATG7 knockdown reversed rIL-17B-induced self-renewal of GC cells. In addition, we showed that IL-17B also promoted K63-mediated ubiquitination of Beclin-1 by mediating the binding of tumor necrosis factor receptor-associated factor 6 to Beclin-1. Silencing IL-17RB expression abrogated the effects of IL-17B on Beclin-1 ubiquitination and autophagy activation in GC cells. Finally, we showed that IL-17B level in the serum of GC patients was positively correlated with IL-17RB expression in GC tissues, and IL-17B could induce IL-17RB expression in GC cells. Overall, the results elucidate the novel functions of IL-17B for CSCs and suggest that the intervention of the IL-17B/IL-17RB signaling pathway may provide new therapeutic targets for the treatment of cancer.

Measuring the effective height for atom gravimeters by applying a frequency jump to Raman lasers.

As the existence of the gravity gradient, the output of gravimeters is actually the gravitational acceleration at the reference instrumental height. Precise knowledge of the reference height is indispensable in the utilization of gravity measurements, especially for absolute gravimeters. Here, we present an interferometric method to measure the distance between the atomic cloud and a reflecting mirror directly, which consequently determines the reference height of our atom gravimeter. This interferometric method is based on a frequency jump of Raman lasers applied at the π pulse of the atom interferometer, which induces an additional phase shift proportional to the interested distance. An uncertainty of 2 mm is achieved here for the distance measurement, and the effect of the gravity gradient on absolute gravity measurements can thus be constrained within 1 µGal. This work provides a concrete-object-based measurement of the reference height for atom gravimeters.

Dual Role of MSC-Derived Exosomes in Tumor Development.

Mesenchymal stem cells (MSCs) are a class of adult stem cells derived from the mesoderm. They can self-renew, have multidirectional differentiation potential, and can differentiate into a variety of mesenchymal tissues. MSCs can produce a large number of exosomes, which can mediate information exchange and transmission between cells in the tumor microenvironment under conditions of rest or stress. Recent studies have reported conflicting findings regarding the effect of MSC-derived exosomes on tumors. Some studies have suggested that MSC-derived exosomes can promote tumor growth and metastasis, but others have reported that they can inhibit tumor cell growth. Here, we investigate the two sides of the debate regarding the effect of MSC-derived exosomes on tumors and analyze the reasons for the divergent findings.

Nasolacrimal Duct Probing for Young Children With Congenital Nasolacrimal Duct Obstructions in China: A 10-Year Systematic Review.

PURPOSE: To investigate the success rate of probing for young children with nasolacrimal duct obstructions and the risk factors involved. METHODS: The medical records of 3,143 patients (3,928 eyes) who received nasolacrimal duct probing in southwest China were collected. These included delivery method, age and gender, preoperative treatments, anesthesia methods, probing procedure, and follow-up clinical records. Then the relationship between the success rates of the probing and a few probable risk factors were analyzed. RESULTS: Children delivered by eutocia were more likely than those delivered by cesarean section to have nasolacrimal duct obstruction. The total success rate of the probing was 85.2%. Patients older than 19 months had a lower completion rate compared with those younger than 1 year (P < .01). In the follow-up observations, the younger age groups were more likely to have higher success rates than the older ones (P < .05) using pairwise comparison. The success rates also had a significant relationship with the type of obstruction and older patients were more likely to have complex obstruction (odds ratio: 1.13, 95% confidence interval: 1.08 to 1.19, P < .001). CONCLUSIONS: This large-scale study proved several factors affect the success rate of nasolacrimal duct probing, and confirmed children delivered by eutocia were more likely to have nasolacrimal duct obstruction. [J Pediatr Ophthalmol Strabismus. 2019;56(6):365-372.].

Marginal Vitamin A Deficiency Affects the Expression Levels and Localization of Retinoic Acid Receptor and Retinoid X Receptor in Rats Meibomian Gland.

PURPOSE: To assess the effects of marginal vitamin A deficiency (MVAD) on rat Meibomian gland morphology as well as retinoic acid receptor (RAR) and retinoid X receptor (RXR) amounts and localization. METHODS: Eight adult female rats were randomized into MVAD and vitamin A normal (VAN) groups, and fed vitamin A-deficient and normal control diets, respectively, for 3 weeks before mating. At postnatal week 4 (P4w), eight newborn animals in both groups were euthanized, respectively. Then, serum retinol levels were analyzed. Meibomian glands from P4w animals were further assessed upon hematoxylin and eosin staining. RAR and RXR gene and protein expression amounts were detected by real time polymerase chain reaction (qRT-PCR), immunofluorescence and western blotting, respectively. RESULTS: Secretory cell nuclei had reduced areas, while the multilayered squamous epithelium of the ductule was overtly thinner in MVAD rats compared with VAN animals. RXR-α showed highest mRNA amounts among all RA receptors; compared with control values, RXR-α showed overtly decreased mRNA amounts in animals with MVAD. In addition, compared with normal rats, MVAD rats had starkly lower RXR-α and RXR-γ expression levels. Furthermore, only the RXR-α protein was detected in the nucleus of cells forming the multilayered squamous epithelium of the ductule in VAN rats. CONCLUSION: RARs and RXRs may be involved in the regulation of Meibomian gland function. RXR-α and 9-cis RA signaling affects Meibomian gland function, and the mechanisms of retinoids on secretory cells and the ductule epithelium may differ. ABBREVIATIONS: MVAD: marginal vitamin A deficiency; RAR: retinoic acid receptor; RXR: retinoid X receptor; VAN: vitamin A normal; RA: retinoic acid; RAREs: retinoic acid responsive elements; HPLC: high performance liquid chromatography; atRA: all-trans retinoic acid; MGD: Meibomian gland dysfunction; CRABPs: cellular retinoic acid-binding proteins.