MYC-targeted genes predict distant recurrence in patients with ocular adnexal extranodal marginal zone lymphoma.

Ocular adnexal extranodal marginal zone lymphoma (OA-EMZL) is the most frequent subtype of ocular adnexal lymphoma, with a high propensity for recurrence. Distant recurrence (DR) as an essential prognostic event has unique clinical risk factors, but whether distinct molecular features exist remains poorly understood. Here, we identified potential biomarkers using proteomic analysis of 27 OA-EMZL samples. The MYC-targeted genes PCNA, MCM6, and MCM4 were identified as candidates. MYC-targeted genes were further identified as the most significantly activated gene set in patients with DR. The candidate genes were verified in samples from 11 patients with DR and 33 matched controls using immunohistochemistry. The 3-year and 5-year AUC values of MCM6 (0.699 and 0.757) were higher than those of Ki-67 (0.532 and 0.592). High expressions of MCM6 and MCM4 were significantly associated with shorter distant recurrence-free survival (Log-rank p = 0.017, Log-rank p = 0.0053). Multivariate Cox regression identified MCM6 expression as an independent risk factor for DR (HR, 6.86; 95% CI, 1.32-35.79; P = 0.02). Knockdown of c-Myc in B cells resulted in decreased MCM6 and MCM4 expression and reduced proliferative capacity. Our results suggest that activation of the MYC-targeted gene is a distinct molecular feature of DR in OA-EMZL. MYC-targeted gene, MCM6, is a promising pathological biomarker for DR.

Comprehensive circular RNA expression profiling with associated ceRNA network in orbital venous malformation.

Purpose: Orbital venous malformation (OVM), the most common type of vascular malformation in adults, has a great impact on both visual and cosmetic factors. Circular RNAs (circRNAs) play important roles in various ophthalmological diseases; however, little is known about their function in the pathogenesis of OVM. Methods: We obtained differentially expressed circRNAs, mRNAs, and miRNAs based on RNA sequencing of four OVM tissues and four normal orbital vascular tissues. The circRNA-mRNA coexpression network and circRNA-miRNA-mRNA and competing endogenous RNA (ceRNA) networks were constructed using miRanda software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify the up- and downregulated mRNAs in the circRNA-miRNA-mRNA ceRNA network. Results: Overall, we identified 45 upregulated and 144 downregulated circRNAs, as well as 2,175 upregulated and 1,274 downregulated mRNAs and 156 upregulated and 168 downregulated miRNAs in OVM samples compared with normal orbital vascular tissues. The expression changes of mRNAs and circRNAs detected by quantitative real-time PCR (qRT-PCR) were in line with the RNA-seq results. Then, a ceRNA regulatory network was constructed with these differentially expressed circRNAs, mRNAs, and miRNAs. GO functional analysis revealed that most related biological processes involved extracellular matrix organization, positive regulation of actin nucleation, and so on, which were thought to be involved in the evolution of OVM. KEGG pathway analysis of upregulated mRNAs showed that mucin-type O-glycan biosynthesis, glycosaminoglycan degradation, and the PI3K (Gene ID: 5290; OMIM: 613089)-AKT (Gene ID: 207; OMIM: 114500) signaling pathway were all enriched in OVM samples. Conclusions: Our study provides novel insight into the regulatory mechanism of circRNAs, miRNAs, and mRNAs in the pathogenesis of OVM.

Automatic orbital computed tomography coordinating method and quantitative error evaluation based on signed distance field.

BACKGROUND: Orbital computed tomography (CT) is commonly used for the diagnosis and digital evaluation of orbital diseases. Yet, this approach requires longer scanning time, increased radiation exposure, and, especially, difficult patient positioning that can affect judgment and data processing. According to high-quality research on orbital imaging, computer-assisted surgery, and artificial intelligent diagnostic development, the correction of a coordinate system is a necessary procedure. Nevertheless, existing manual calibration methods are challenging to reproduce and there is no objective evaluation system for errors. PURPOSE: To establish a method for automatic calibration of orbital CT images and implementation of quantitative error evaluation. MATERIAL AND METHODS: A standard three-dimensional (3D) orbit model was manually adjusted, and optimized orbital models were reconstructed based on the initial registration of the skull-bound directed bounding box and the registration of the mutual information method. The calibration error was calculated based on the signed distance field. Seventeen cases of orbital CT were quantitatively evaluated. RESULTS: A new method for automatic calibration and quantitative error evaluation for orbital CT was established. The calibrated model error with ±2 mm accounted for 81.61% ± 6.91% of the total models, and the error of ±1 mm accounted for 53.49% ± 7.07% of the total models. CONCLUSION: This convenient tool for orbital CT automatic calibration may promote the related quantitative research based on orbital CT. The automated operation and small error are beneficial to the popularization and application of the tool, and the quantitative evaluation facilitates other coordinate systems.

Modified deep anterior lamellar dissection for corneal opacity during vitrectomy: case reports.

BACKGROUND: To introduce a modified deep anterior lamellar dissection technique to improve visibility during surgery for vitreoretinal diseases with coexisting corneal opacity. CASE PRESENTATION: Two patients with retinal detachment and coexisting corneal blood staining or corneal decompensation underwent modified deep anterior lamellar dissections followed by vitrectomy. The modified deep anterior lamellar dissection techniques, unlike the dissection and removal of corneal lamellar in a typical deep anterior lamellar keratoplasty, included the creation and preservation of a deep lamellar corneal flap, the retroillumination to visualize and easily remove the remaining opaque stroma on the Descemet membrane, and the big air bubble technique in the eye with endothelial decompensation. The patient's own cornea flap was sutured back after vitrectomy was done. The modified dissection techniques provided adequate fundus view during vitrectomy while removing as less corneal tissue as possible and decreasing the surgical complications and the requirement of a fresh cornea. Postoperatively, in case 1, the corneal blood staining was gradually absorbed and the vision improved from light perception to counting fingers. In case 2, even though the cornea remained cloudy and the vision was poor, the cornea endothelial decompensation was stable and asymptomatic. Both retinas were attached after silicone oil removal at 6-month follow-up. CONCLUSIONS: This modified and limited deep anterior lamellar corneal dissection procedure appears to be a useful alternative to penetrating keratoplasty, ophthalmic endoscope and temporary keratoprosthesis during the vitrectomy with coexisting corneal opacity.

Impact of Full-Incision Double-Eyelid Blepharoplasty on Tear Film Dynamics and Dry Eye Symptoms in Young Asian Females.

BACKGROUND: Dry eye symptoms as a complication of double-eyelid blepharoplasty are controversial. This article evaluates tear film dynamics and changes in dry eye symptoms after cosmetic double-eyelid blepharoplasty in young Asian female. METHODS: One hundred and twenty patients underwent full-incisional double-eyelid blepharoplasty. Subjective and objective parameters were documented before surgery, at 1 week, 1 month and 3 months post-surgery, which included Ocular Surface Disease Index questionnaire (OSDI), tear meniscus height (TMH), noninvasive breakup time (NIBUT), Schirmer I test, corneal and conjunctival fluorescein staining scores, and palpebral fissure height. Dry eyes were defined based on the DEWS II criteria: OSDI ≥ 13 points and NIBUT < 10 s. Patients were divided into two groups, group A included patients with redundant skin, while group B included patients with absence of redundant skin. RESULTS: The incident rate of dry eyes preoperatively, and at 1 week, 1 month and 3 months were 12.5%, 12.5%, 32.5%, and 16.67%. OSDI scores were significantly increased at 1 week (9.71 ± 10.07, P < 0.001) and 1 month (11.35 ± 12.28, P < 0.001) postoperatively. A significant increase in TMH, NIBUT and Schirmer's test I values were observed at 1 week post-surgery (P < 0.001). Patients in group A showed higher OSDI scores compared to group B at 1 week and 1 month (P = 0.051) post-surgery, and the other variables showed no difference between the groups. CONCLUSIONS: Cosmetic double-eyelid blepharoplasty may temporarily affect tear film dynamics and aggravate dry eye symptoms in young females. However, these changes generally recover 3 months postoperatively. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Lyar Is a New Ligand for Retinal Pigment Epithelial Phagocytosis.

Phagocytosis is critical to tissue homeostasis, as highlighted by phagocytosis defect of retinal pigment epithelial (RPE) cells with debris accumulation, photoreceptor degeneration and blindness. Phagocytosis ligands are the key to delineating molecular mechanisms and functional roles of phagocytes, but are traditionally identified in individual cases with technical challenges. We recently developed open reading frame phage display (OPD) for phagocytosis-based functional cloning (PFC) to identify unknown ligands. One of the identified ligands was Ly-1 antibody reactive clone (Lyar) with functions poorly defined. Herein, we characterized Lyar as a new ligand to stimulate RPE phagocytosis. In contrast to its reported nucleolar expression, immunohistochemistry showed that Lyar was highly expressed in photoreceptor outer segments (POSs) of the retina. Cytoplasmic Lyar was released from apoptotic cells, and selectively bound to shed POSs and apoptotic cells, but not healthy cells. POS vesicles engulfed through Lyar-dependent pathway were targeted to phagosomes and colocalized with phagosome marker Rab7. These results suggest that Lyar is a genuine RPE phagocytosis ligand, which in turn supports the validity of OPD/PFC as the only available approach for unbiased identification of phagocytosis ligands with broad applicability to various phagocytes.

Novel mutations in the RB1 gene from Chinese families with a history of retinoblastoma.

Retinoblastoma is an aggressive eye cancer that develops during infancy and is divided into two clinical types, sporadic and heritable. RB1 has been identified as the only pathological gene responsible for heritable retinoblastoma. Here, we identified 11 RB1 germline mutations in the Han pedigrees of 17 bilateral retinoblastoma patients from China. Four mutations were nonsense mutations, five were splice site mutations, and two resulted in a frame shift due to an insertion or a deletion. Three of the mutations had not been previously reported, and the p.Q344L mutation occurred in two generations of retinoblastoma patients. We investigated phenotypic-genotypic relationships for the novel mutations and showed that these mutations affected the expression, location, and function of the retinoblastoma protein. Abnormal protein localization was observed after transfection of the mutant genes. In addition, changes in the cell cycle distribution and apoptosis rates were observed when the Saos-2 cell line was transfected with plasmids encoding the mutant RB1 genes. Our findings expand the spectrum of known RB1 mutations and will benefit the investigation of RB1 mutation hotspots. Genetic counseling can be offered to families with heritable RB1 mutations.

A modified staged surgical intervention for blepharophimosis-ptosis-epicanthus inversus syndrome: 125 cases with encouraging results.

BACKGROUND: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant condition characterized by typical eyelid malformations that include blepharophimosis, ptosis, epicanthus inversus, and telecanthus. METHODS: We retrospectively reviewed 125 consecutive BPES patients who underwent staged surgical intervention from July 2003 to December 2011. All patients underwent initial medial and lateral canthoplasties, followed by blephroptosis correction 6 to 12 months afterward. The parameters that were studied included horizontal palpebral fissure length (PFL), vertical interpalpebral fissure height, inner intercanthal distance (IICD), the ratio of IICD to PFL, and frontalis function (FF). Facial photographs were taken preoperatively and postoperatively. Paired and group t tests were used for statistical analysis to evaluate surgical outcomes. RESULTS: After consecutive operations, the mean PFL increased from 19.5 to 25.7 mm (mean difference, 6.2 mm; P < 0.01). The mean interpalpebral fissure height increased from 3.4 to 8.5 mm (mean difference, 5.1 mm; P < 0.01). The mean IICD decreased from 38.0 to 30.9 mm (mean difference, 7.1 mm; P < 0.01). The mean FF was 7.3 mm for BPES patients approximately 5 years old and 10.4 mm for patients approximately 7 years old. There was no difference between children who underwent muscle flap suspension and healthy children of the same age (P > 0.05). CONCLUSIONS: The modified staged surgical intervention, including Y-V flap, von Ammon, and frontalis muscle flap suspension, provided effective results both in function and cosmesis for BPES. The FF was not weakened by surgery.

Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis.

Tubby and tubby-like protein 1 (Tulp1) are newly identified phagocytosis ligands to facilitate retinal pigment epithelium (RPE) and macrophage phagocytosis. Both proteins without classical signal peptide have been demonstrated with unconventional secretion. Here, we characterized them as novel MerTK ligands to facilitate phagocytosis. Tulp1 interacts with Tyro3, Axl and MerTK of the TAM receptor tyrosine kinase subfamily, whereas tubby binds only to MerTK. Excessive soluble MerTK extracellular domain blocked tubby- or Tulp1-mediated phagocytosis. Both ligands induced MerTK activation with receptor phosphorylation and signalling cascade, including non-muscle myosin II redistribution and co-localization with phagosomes. Tubby and Tulp1 are bridging molecules with their N-terminal region as MerTK-binding domain and C-terminal region as phagocytosis prey-binding domain (PPBD). Five minimal phagocytic determinants (MPDs) of K/R(X)(1-2)KKK in Tulp1 N-terminus were defined as essential motifs for MerTK binding, receptor phosphorylation and phagocytosis. PPBD was mapped to the highly conserved 54 amino acids at the C-terminal end of tubby and Tulp1. These data suggest that tubby and Tulp1 are novel bridging molecules to facilitate phagocytosis through MerTK.

The role of Bax and Bcl-2 in gemcitabine-mediated cytotoxicity in uveal melanoma cells.

Gemcitabine (GEM), a new cytotoxic agent, was shown to be effective against uveal melanoma (UM) which is noted for its resistance to chemotherapy. In this study, we found the different sensitivities to GEM in UM cell lines and identified apoptotic cell death as the cause of GEM cytotoxicity. Both UM cell lines showed an increase in Bax protein levels and activation of cleaved Caspase 3. Additionally, SP6.5 cells showed a gradual increase in Bcl-2 expression over time, whereas VUP cells showed almost none. After interfering in the expression of Bcl-2, the sensitivity to GEM was obviously enhanced in SP6.5 cells. These results suggest that an increase in Bax plays a crucial role in apoptotic cell death induced by GEM in the absence of p53. Moreover, inhibition of Bcl-2 expression can efficiently enhance the cytotoxic effect of, and sensitivity to, GEM in UM cells.

Prediction model of radiotherapy outcome for Ocular Adnexal Lymphoma using informative features selected by chemometric algorithms.

BACKGROUND: Ocular Adnexal Lymphoma (OAL) is a non-Hodgkin's lymphoma that most often appears in the tissues near the eye, and radiotherapy is the currently preferred treatment. There has been a controversy regarding the prognostic factors for systemic failure of OAL radiotherapy, the thorough evaluation prior to receiving radiotherapy is highly recommended to better the patient's prognosis and minimize the likelihood of any adverse effects. PURPOSE: To investigate the risk factors that contribute to incomplete remission in OAL radiotherapy and to establish a hybrid model for predicting the radiotherapy outcomes in OAL patients. METHODS: A retrospective chart review was performed for 87 consecutive patients with OAL who received radiotherapy between Feb 2011 and August 2022 in our center. Seven image features, derived from MRI sequences, were integrated with 122 clinical features to form comprehensive patient feature sets. Chemometric algorithms were then employed to distill highly informative features from these sets. Based on these refined features, SVM and XGBoost classifiers were performed to classify the effect of radiotherapy. RESULTS: The clinical records of from 87 OAL patients (median age: 60 months, IQR: 52-68 months; 62.1% male) treated with radiotherapy were reviewed. Analysis of Lasso (AUC = 0.75, 95% CI: 0.72-0.77) and Random Forest (AUC = 0.67, 95% CI: 0.62-0.70) algorithms revealed four potential features, resulting in an intersection AUC of 0.80 (95% CI: 0.75-0.82). Logistic Regression (AUC = 0.75, 95% CI: 0.72-0.77) identified two features. Furthermore, the integration of chemometric methods such as CARS (AUC = 0.66, 95% CI: 0.62-0.72), UVE (AUC = 0.71, 95% CI: 0.66-0.75), and GA (AUC = 0.65, 95% CI: 0.60-0.69) highlighted six features in total, with an intersection AUC of 0.82 (95% CI: 0.78-0.83). These features included enophthalmos, diplopia, tenderness, elevated ALT count, HBsAg positivity, and CD43 positivity in immunohistochemical tests. CONCLUSION: The findings suggest the effectiveness of chemometric algorithms in pinpointing OAL risk factors, and the prediction model we proposed shows promise in helping clinicians identify OAL patients likely to achieve complete remission via radiotherapy. Notably, patients with a history of exophthalmos, diplopia, tenderness, elevated ALT levels, HBsAg positivity, and CD43 positivity are less likely to attain complete remission after radiotherapy. These insights offer more targeted management strategies for OAL patients. The developed model is accessible online at: https://lzz.testop.top/.

Predicting the risk of distant and local recurrence for patients with ocular adnexal extranodal marginal zone lymphoma: a matched case-control study.

BACKGROUND/AIMS: Extranodal marginal zone lymphoma of ocular adnexa (OA-EMZL) is the most frequent type of ocular adnexal lymphomas, with a high rate of disease recurrence. Precise patient stratification based on disease recurrence is understudied. This study aims to identify risk factors of distant recurrence (DR) and local recurrence (LR) to construct a prognostic model optimising rapid decision of therapeutic strategies. METHODS: A total of 104 patients diagnosed with OA-EMZL between January 2011 and February 2020 were enrolled. Propensity score matching was performed for DR and LR groups. A nomogram was generated using a multivariate Cox proportional hazards model. RESULTS: After matching, different independent risk factors of DR and LR were identified. Monocyte percentage (p=0.015) and M category >0 (p=0.043) were significant independent risk factors of DR. Epiphora (p<0.001) was the significant independent risk factor of LR. Three factors (monocyte percentage, M category >0, age >60) were integrated into the nomogram to predict the risk of DR. It had a relatively better discriminative ability for distant recurrence-free survival (C-index: 3-year, 0.784; 6-year, 0.801) than IPI score (C-index: 3-year, 0.663; 6-year, 0.673) in the cohort of all patients. CONCLUSION: Our analyses suggested DR and LR as two distinct prognostic events, and additionally identified novel risk factors of them. The nomogram may serve as a practical tool for the prognostic estimation and rapid decision of therapeutic strategies for patients with OA-EMZL.

Binocular head-mounted chromatic pupillometry can detect structural and functional loss in glaucoma.

Aim: The aim of this study is to evaluate the utility of binocular chromatic pupillometry in detecting impaired pupillary light response (PLR) in patients with primary open-angle glaucoma (POAG) and to assess the feasibility of using binocular chromatic pupillometer in opportunistic POAG diagnosis in community-based or telemedicine-based services. Methods: In this prospective, cross-sectional study, 74 patients with POAG and 23 healthy controls were enrolled. All participants underwent comprehensive ophthalmologic examinations including optical coherence tomography (OCT) and standard automated perimetry (SAP). The PLR tests included sequential tests of full-field chromatic stimuli weighted by rods, intrinsically photosensitive retinal ganglion cells (ipRGCs), and cones (Experiment 1), as well as alternating chromatic light flash-induced relative afferent pupillary defect (RAPD) test (Experiment 2). In Experiment 1, the constricting amplitude, velocity, and time to maximum constriction/dilation were calculated in three cell type-weighted responses, and the post-illumination response of ipRGC-weighted response was evaluated. In Experiment 2, infrared pupillary asymmetry (IPA) amplitude and anisocoria duration induced by intermittent blue or red light flashes were calculated. Results: In Experiment 1, the PLR of POAG patients was significantly reduced in all conditions, reflecting the defect in photoreception through rods, cones, and ipRGCs. The variable with the highest area under the receiver operating characteristic curve (AUC) was time to max dilation under ipRGC-weighted stimulus, followed by the constriction amplitude under cone-weighted stimulus and the constriction amplitude response to ipRGC-weighted stimuli. The impaired PLR features were associated with greater visual field loss, thinner retinal nerve fiber layer (RNFL) thickness, and cupping of the optic disk. In Experiment 2, IPA and anisocoria duration induced by intermittent blue or red light flashes were significantly greater in participants with POAG than in controls. IPA and anisocoria duration had good diagnostic value, correlating with the inter-eye asymmetry of visual field loss. Conclusion: We demonstrate that binocular chromatic pupillometry could potentially serve as an objective clinical tool for opportunistic glaucoma diagnosis in community-based or telemedicine-based services. Binocular chromatic pupillometry allows an accurate, objective, and rapid assessment of retinal structural impairment and functional loss in glaucomatous eyes of different severity levels.

Evaluation of the Glaucomatous Macular Damage by Chromatic Pupillometry.

INTRODUCTION: This study aimed to examine the performance of binocular chromatic pupillometry for the objective and rapid detection of primary open-angle glaucoma (POAG), and to explore the association between pupillary light response (PLR) features and structural glaucomatous macular damage. METHODS: Forty-six patients (mean age 41.00 ± 13.03 years) with POAG and 23 healthy controls (mean age 42.00 ± 11.08 years) were enrolled. All participants underwent sequenced PLR tests of full-field, superior/inferior quadrant-field chromatic stimuli using a binocular head-mounted pupillometer. The constricting amplitude, velocity, and time to max constriction/dilation, and the post-illumination pupil response (PIPR) were analyzed. The inner retina thickness and volume measurements were determined by spectral domain optical coherence tomography. RESULTS: In the full-field stimulus experiment, time to pupil dilation was inversely correlated with perifoveal thickness (r = - 0.429, P < 0.001) and perifoveal volume (r = - 0.364, P < 0.001). Dilation time (AUC 0.833) showed good diagnostic performance, followed by the constriction amplitude (AUC 0.681) and PIPR (AUC 0.620). In the superior quadrant-field stimulus experiment, time of pupil dilation negatively correlated with inferior perifoveal thickness (r = - 0.451, P < 0.001) and inferior perifoveal volume (r = - 0.417, P < 0.001). The dilation time in response to the superior quadrant-field stimulus showed the best diagnostic performance (AUC 0.909). In the inferior quadrant-field stimulus experiment, time to pupil dilation (P < 0.001) correlated well with superior perifoveal thickness (r = - 0.299, P < 0.001) and superior perifoveal volume (r = - 0.304, P < 0.001). CONCLUSION: The use of chromatic pupillometry offers a patient-friendly and objective approach to detect POAG, while the impairment of PLR features may serve as a potential indicator of structural macular damage.

Potentiation of tumor radiotherapy by a radiation-inducible oncolytic and oncoapoptotic adenovirus in cervical cancer xenografts.

The p53 tumor suppressor pathway is impaired in more than 90% of cervical cancers and cancer-derived cell lines as a result of infection by human papillomavirus (HPV). The HPV E6 oncoprotein forms complexes with p53 and promotes its degradation via ubiquitin-dependent mechanism. In our study, we attempted to improve the clinical outcomes of this combined therapy by modifying the p53-targeted adenovirus to become radiation-responsive. The antitumor adenovirus was constructed by inserting a radiation-responsive expression cassette composed of the promoter of early growth response-1 (Egr-1) and the proapoptotic protein TRAIL. We showed that the addition of adenovirus containing Egr-1/TRAIL significantly increased cell death and apoptosis caused by radiotherapy. In mice bearing xenograft tumors, intratumoral administration of the Egr-1/TRAIL adenovirus followed by radiation significantly reduced tumor growth and enhanced tumor survival. Our Egr-1/TRAIL adenoviral gene product may offer a novel "one-two punch" tumor therapy for cervical cancers not only by potentiating radiation treatment but also by preserving p53 defect-specific tumor killing of the oncolytic adenovirus.

The combination of polyalanine expansion mutation and a novel missense substitution in transcription factor FOXL2 leads to different ovarian phenotypes in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) patients.

STUDY QUESTION: What are the implications of multiple alterations of the forkhead box L2 (FOXL2) gene in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) patients? SUMMARY ANSWER: A multi-mutation of FOXL2, consisting of the expansion of the polyalanine tract from 14 to 24 residues (FOXL2-Ala24), an novel Y186C substitution from c.557A>G, and a synonymous variant (c.505G>A), had a cumulative effect on ovarian phenotypes in BPES patients. WHAT IS KNOWN ALREADY: Mutations in FOXL2, a gene encoding a forkhead transcription factor cause BPES. Overall, the expansion of the polyalanine tract of FOXL2 from 14 to 24 residues (FOXL2-Ala24) accounts for 30% of intragenic mutations. STUDY DESIGN, SIZE, DURATION: In this study, patients from seven BPES families and six sporadic cases were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: We conducted an extensive clinical, hormonal and functional study in 20 patients carrying the expansion of the polyalanine tract of FOXL2 associated with BPES. A multi-mutation of FOXL2 was detected in one BPES family that showed more severe BPES symptoms. Subcellular localization and transactivation studies were performed for the constructs of FOXL2-Ala24, Y186C and FOXL2-Ala24-Y186C. MAIN RESULTS: We described the first multi-mutation of FOXL2 (c. [672_701dup30; 557A>G]) that leads to the polyalanine expansion of +10 residues (FOXL2-Ala24) combined with an Y186C substitution and a synonymous variant in a Chinese BPES family. This multi-mutation genotype was associated with more serious BPES clinical manifestations and the development of esotropia in the right eye. In in vitro studies, the multi-mutation affected the function of FOKL2 on the StAR promoter and DK3, and induced more aggressive aggregation and mislocalization of FOXL2 protein. The synonymous variant, while not affecting amino acid coding, causes a change in the RNA stem-loop structure. LIMITATIONS, REASONS FOR CAUTION: The multi-mutation of FOXL2 was detected in one BPES family and it needs to be validated further by more BPES subjects. WIDER IMPLICATIONS OF THE FINDINGS: The results of our study contribute new insights into the research field of BPES caused by the multi-mutation of FOXL2. STUDY FUNDING/COMPETING INTERESTS: This study was supported by Shanghai Leading Academic Discipline Project (Grant number S30205) and Shanghai Jiao Tong University School of Medicine Doctor Innovation Fund (Grant number 201131). The authors have no competing interests to declare.

Combined treatment with an oncolytic adenovirus and antitumor activity of vincristine against retinoblastoma cells.

Treatment trends of retinoblastoma (RB) have gradually evolved from eye enucleation and external radiation to local treatment. Combined treatment with an oncolytic virus and chemotherapy is currently a new method in RB treatment. To investigate the therapeutic effect of oncolytic adenovirus SG600 in combination with vincristine (VCR) on retinoblastoma in vitro, the cell viability, cell cycle effects and apoptotic activity of HXO-RB(44) cells treated with SG600, VCR or SG600 plus VCR were measured using a cell counting kit-8-based procedure and flow cytometry. Western blot analysis for Akt, p-Akt, p-p53 and p-Rb protein was performed to investigate the underlying mechanisms of combined therapy. The combination therapy exerted a synergistic antitumor effect via a type of G(2)/M and S phase arrest rather than the induction of apoptosis. The combination of VCR and SG600 further reduced Akt phosphorylation compared with cells treated with VCR alone, suggesting that SG600 could overcome chemoresistance, perhaps by down-regulating Akt in RB cells. An increase in the expression of p-p53 and decrease in p-Rb expression in HXO-RB(44) after co-treatment might be associated with cell cycle block. Western blot examination revealed that VCR might enhance SG600 replication. These results suggest that viro-chemo combination therapy is a feasible and potentially promising approach for the treatment of retinoblastoma.

Elasticity and damping ratio measurement of droplets on super-hydrophobic surfaces.

The measurement of the droplets' elasticity is vitally important in microfluidic and ink-jet printing. It refers to the ability of the droplet to restore its original shape and strong robustness. This study investigated a novel method to measure elasticity. The plate coated with super-hydrophobic layers pressed on a droplet and the elastic force was recorded by an electronic balance. Meanwhile, a mathematical model was constructed to calculate the changes of the droplet area under the force. The measurement showed that external work mainly converts into surface energy and the damping ratio increases from 0.068 to 0.261 with the increase of mass fraction from 0 to 80 wt%. It also indicates that the novel method can accurately and efficiently measure the elasticity of droplets.

Transumbilical Single-incision Laparoscopic Surgery for Harvesting Rib and Costal Cartilage.

The study aimed to introduce a rib and costal cartilage harvesting surgery by transumbilical single-incision laparoscopy and evaluate its efficiency and safety. Methods: Patients who underwent rib and costal cartilage harvest under different approaches (direct open approach and transumbilical) were collected in this retrospective study. The differences in the pain scores [visual analog scale (VAS)], postoperative appearance, and complications were compared between the two groups at 1, 2, 3, and 7 days after surgery. In addition, based on the minimal clinically important difference and the generalized estimating equation, the differences were compared between the two groups in terms of the VAS score. Results: On postoperative day 1, the VAS scores of the direct open approach group and the transumbilical group were significantly different, that is, 7.29 and 6.10, respectively (P < 0.001). Also, the generalized estimating equation results were different (P < 0.001). An interaction was observed between different groups and days, that is, a statistical difference was observed in the VAS score between the two groups (P < 0.001). In terms of aesthetics and complications, patients from the transumbilical group had no scars on the chest wall and no obvious postoperative complications. Conclusions: Transumbilical single-incision laparoscopic surgery is an innovative surgical approach for harvesting ribs and costal cartilage, which leaves no scars on the skin of the chest wall and has the advantages of slight postoperative pain, quick recovery, and fewer complications. This novel surgery is beneficial to patients with higher aesthetic requirements.

Diagnosis and treatment of needle retention after blepharoplasty.

BACKGROUND: Needle retention is a rare but dangerous complication in ophthalmologic and oculoplastic surgery, with a limited literature detailing this issue. This study aimed to summarize the characteristics of needle retention after blepharoplasty, introduce intervention experience, and offer preventive suggestions. METHODS: This retrospective case series included six eyes of 6 consecutive Chinese patients that received prior initial blepharoplasties and presented to the emergency unit. Demographics, clinical features, and complications of all patients were collected, and diagnoses were made by three-dimensional computed tomography (3D-CT) scanning with volume rendered technique. All needles were removed by minimally invasive surgery. RESULTS: All patients accepted their initial blepharoplasty either at private cosmetic clinics (5/6) or at a friend's home (1/6). Only on using 3D-CT scanning, could the location of retained needles be confirmed. Needles were located in the lateral part of the left-sided eyelid for all patients, and resided in the orbicularis layer (5/6) or periosteum (1/6). In needle removal surgeries, four patients (2/3) accepted percutaneous small incision method, and the remaining two (1/3) were treated via their existing wounds. No intra- or postoperative complications during operations or follow up were found. CONCLUSIONS: Diagnosis of needle retention is based on histories, and use of 3D-CT scanning is recommended for location. The retained needle should be removed promptly before its potentially devastating migration begins, and small incisional surgery with an aesthetic design is effective. Authentic private and public institutionally qualified surgeons in cosmetic surgery should be validated and supervised by the Government.