Risk factors and prediction model for delayed bleeding after cold snare polypectomy: a retrospective study.

BACKGROUND: Delayed bleeding (DB) is a serious complication after cold snare polypectomy (CSP) for polyps in the colon. The present study aimed to investigate the incidence and risk factors of DB after CSP and to develop a risk-scoring model for predicting DB. METHODS: A retrospective study was conducted in four Chinese medical institutions. 10650 patients underwent CSP from June 2019 to May 2023. The study analyzed the rate of DB and extracted the general clinical information and polyp-related information of patients with postoperative DB. As a control, non-DB patients who received CSP at the same 4 hospitals were analyzed. A multivariate Cox regression analysis was performed to develop the prediction model. The model was further validated using a Kaplan-Meier log-rank analysis, receiver operating characteristic curve (ROC) plot and risk plot. RESULTS: In our study, we found a 0.24% rate of DB and the risk factors were history of hypertension, hyperlipidemia, antithrombotics use, antiplatelet use, anticoagulant use, abdominal operation, sigmoid colon lesion, hematoma, cold snare defect protrusion, polyp size, wound size, the grade of wound bleeding, and morphology of Ip. These factors were incorporated into the prediction model for DB after CSP. For 1, 3, and 5 days of bleeding, the AUC of the ROC curve was 0.912, 0.939, and 0.923, respectively. The Kaplan-Meier analysis indicated that the high-risk group had a significantly higher risk of DB than the low-risk group. CONCLUSIONS: This study screened the risk factors and established a prediction model of DB after CSP. The results may help preventing and reducing the DB rate after CSP of colorectal polyps.

Drug supply and assurance: a cross-sectional study of drug shortage monitoring varieties in China.

BACKGROUND: Drug shortage is a worldwide problem that seriously threatens public health. China released the most comprehensive list of key drug shortage monitoring varieties ever in 2022. We aim to analyze the attributes and characteristics of the medicines within the list to provide a reference for improving China's supply security of shortage drugs. METHODS: We used public data to extract information on drug types, dosage forms, indications, classification of clinical uses, whether they were included in medical catalogs such as the National Essential Drugs, and the number of drug and active pharmaceutical ingredient (API) manufacturers. A descriptive statistical analysis was used. RESULTS: Of the 980 drugs on the list, 99.59% were chemicals and 92.65% were injectables. Drugs for blood and hematopoietic organs, the cardiovascular system, and the digestive tract and metabolism ranked among the top three shortages. Verification of the medical catalogs showed that 90.41% of the drugs belonged to the national essential drugs, 95.10% were medicare drugs, 2.55% were volume-based procurement drugs, and 14.70% were for rare diseases, and 42.04% were for children. In terms of drug supply capacity, 21.33% of drug approvals are less than 10, and there were even 26 drugs for exclusive production, close to 90% of manufacturers need to purchase APIs from outside. Among the 256 APIs included in the list, 152 APIs had less than 10 manufacturers, and there were even 5 APIs produced by only one enterprise nationwide. CONCLUSIONS: The situation of drug shortages in China was severe and complex, with serious shortages of medicines adapted to basic medical and healthcare needs and clinically necessary medicines, and a need to improve the production capacity of drugs and the ability to supply APIs. We recommend strengthening drug monitoring and stockpiling and accelerating the approval of shortage drugs to improve drug supply security.

Robust, Ultrafast and Reversible Photoswitching in Bulk Polymers Enabled by Octupolar Molecule Design.

Improving the photoswitching rate and robustness of photochromic molecules in bulk solids is paramount for practical applications but remains an on-going challenge. Here, we introduce an octupolar design paradigm to develop a new family of visible light organic photoswitches, namely multi-branched octupolar Stenhouse Adducts (MOPSAs) featuring a C3-symmetrical A3-(D-core) architecture with a dipolar donor-acceptor (D-A) photochrome in each branch. Our design couples multi-dimensional geometric and electronic effects of MOPSAs to enable robust ultrafast reversible photoswitching in bulk polymers. Specifically, the optimal MOPSA (4 wt %) in commercial polyurethane films accomplishes nearly 100 % discoloration in 6 s under visible light with ∼ 100 % thermal-recovery in 17.4 s at 60 °C, while the acquired kinetics constants are 3∼7 times that of dipolar DASA counterpart and 1∼2 orders of magnitude higher than those of reported DASAs in polymers. Importantly, the MOPSA-doped polymer films sustain 500 discoloration/recovery cycles with slow degradation, superior to the existing DASAs in polymers (≤30 cycles). We discover that multi-dipolar coupling in MOPSA enables enhanced polarization and electron delocalization, promoting the rate-determining thermal cyclization, while the branched and non-planar geometry of MOPSA induces large free volume to facilitate the isomerization. This design can be extended to develop spiropyran or azobenzene-based ultrafast photochromic films. The superior photoswitching performance of MOPSAs together with their high-yield and scalable synthesis and facile film processing inspires us to explore their versatile uses as smart inks or labels for time-temperature indicators, optical logic encryption and multi-levelled data encryption.

m6A writer WTAP targets NRF2 to accelerate bladder cancer malignancy via m6A-dependent ferroptosis regulation.

Recent evidence have indicated that ferroptosis, a novel iron-dependent form of non-apoptotic cell death, plays a critical role in human cancers. Besides, emerging literatures have revealed the ovel function of N6-methyladenosine (m6A) in bladder cancer physiological. However, the underlying mechanism of m6A on bladder cancer is still unclear. Here, present work revealed that m6A methyltransferase ('writer') WTAP up-regulated in bladder cancer tissue and cells, indicating the poor prognosis of bladder cancer patients. Functionally, gain/loss-of-functional experiments illustrated that WTAP promoted the viability of bladder cancer cells and inhibited the erastin-induced ferroptosis. Mechanistically, there was a remarkable m6A modification site on 3'-UTR of endogenous antioxidant factor NRF2 RNA and WTAP could install its methylation. Moreover, m6A reader YTHDF1 recognized the m6A site on NRF2 mRNA and enhanced its mRNA stability. Therefore, these findings demonstrated potential therapeutic strategyies for bladder cancer via m6A-dependent manner.

A single-cell transcriptomic atlas of the human ciliary body.

The ciliary body critically contributes to the ocular physiology with multiple responsibilities in the production of aqueous humor, vision accommodation and intraocular immunity. Comparatively little work, however, has revealed the single-cell molecular taxonomy of the human ciliary body required for studying these functionalities. In this study, we report a comprehensive atlas of the cellular and molecular components of human ciliary body as well as their interactions using single-cell RNA sequencing (scRNAseq). Cluster analysis of the transcriptome of 14,563 individual ciliary cells from the eyes of 3 human donors identified 14 distinct cell types, including the ciliary epithelium, smooth muscle, vascular endothelial cell, immune cell and other stromal cell populations. Cell-type discriminative gene markers were also revealed. Unique gene expression patterns essential for ciliary epithelium-mediated aqueous humor inflow and ciliary smooth muscle contractility were identified. Importantly, we discovered the transitional states that probably contribute to the transition of ciliary macrophage into retina microglia and verified no lymphatics in the ciliary body. Moreover, the utilization of CellPhoneDB allowed us to systemically infer cell-cell interactions among diverse ciliary cells including those that potentially participate in the pathogenesis of glaucoma and uveitis. Altogether, these new findings provide insights into the regulation of intraocular pressure, accommodation reflex and immune homeostasis under physiological and pathological conditions.

Predation risk affects the ecotoxicity evaluation of antibiotics: Population growth and antioxidase activity in the ciliate Paramecium jenningsi.

Although predation risk exists under natural conditions, its role is usually ignored when evaluating the ecotoxicity of environmental contaminants, and the interaction between predation risk and antibiotic ecotoxicity is not yet clear. To investigate the nonconsumptive effects (NCEs) of predation on the ecotoxicity evaluation of antibiotics, the median lethal concentration (LC50), relative population growth rate (RGR), and activities of three antioxidases were measured in the ciliate Paramecium jenningsi exposed to graded concentrations of the antibiotics nitrofurazone (NFZ) or erythromycin (ERY) in the presence or absence of a predator, i.e., the ciliate Didinium nasutum. The results showed that (1) NCEs significantly reduced the LC50 of NFZ but had no effect on that of ERY; (2) predation pressure alone had no significant effect on the inhibitory rate of the P. jenningsi population, but the interaction with NFZ was synergistic, while that with CRY was additive; (3) the concentrationresponse (i.e., mortality) model for each antibiotic exposure with and without predation pressure differed significantly in the parameter slope; (4) RGRs were significantly reduced by antibiotic exposure or NCEs; only in NFZ-exposed groups did the RGRs decrease linearly with increasing exposure concentration; and (5) the activities of all three antioxidases significantly increased due to NCEs or following exposure to antibiotics. In brief, NCEs were detected in P. jenningsi, and these had additive or synergistic effects on antibiotic ecotoxicity, but their magnitude depended on the properties and exposure concentrations of the antibiotics. Our findings suggest that it is necessary to consider the roles of NCEs in the ecotoxicity evaluation of environmental contaminants.

Hydrogen Bond-Enhanced Nanoaggregation and Antisolvatochromic Fluorescence for Protein-Recognition by Si-Coumarins.

Silicon-substituted coumarin (SiC) was established as a substantial family of both intramolecular and intermolecular hydrogen bond (H-bond) enhanced fluorescent probes for sensitively tracking proteins in vivo through the assemble and disassemble of its nanoaggregates. The intramolecular H-bond in SiC has led to significant aggregation, antisolvatochromism, and strong fluorescence with bathochromically shifted spectra into far-red or near-infrared (NIR) regions in polar, protic environments. Without further furnishing with organic linkers, the compact skeleton of SiC bearing H-bond has ensured sensitively and selectively sensing the targeting proteins with the protic reaction pockets through efficient disassemble of the aggregates. In the existence of strong intermolecular H-bonds with the target protein pocket, SiC resolved as high as >250-fold fluorescence enhancement. Selectively tracking proteins, including human serum albumin, human carbonic anhydrase (hCAII), avidin, SNAP-tag protein, and translocator protein, has confirmed SiC a versatile skeleton for sensitively monitoring proteins in complicated biological systems.

Circular RNA circMTO1 suppressed the progression of renal cell carcinoma progression by sponging miR-211 and miR-204.

Despite considerable improvements in renal cell carcinoma (RCC) diagnostic and therapeutic strategy, the clinical prognosis of patients is far from satisfactory due to its recurrence and metastasis. Here, we attempted to explore the role of circMTO1 in RCC progression, and the underlying mechanism was further elucidated. We first detected the expression of circMTO1 in 90 pairs of RCC tissues and adjacent normal tissues using qRT-PCR. Besides, circMTO1, miR-211, miR-204 and KLF6 expression levels in RCC cells were also measured using qRT-PCR. MTT assay, cell migration, flow cytometry analysis, qRT-PCR and western blotting analysis were applied to evaluating the effect of circMTO1 in RCC cells. The bioinformatics analysis and the rescue experiment were devoted to the underlying mechanism. The results demonstrated CircMTO1 expression was significantly down-regulated in RCC tissues and cell lines. Besides, CircMTO1 inhibited cell proliferation, migration and invasion, induced apoptosis in RCC cells. In addition, CircMTO1 serves as a sponge for miR-211 and miR-204, KLF6 is a direct target of miR-211 and miR-204. Furthermore, circMTO1 and KLF6 overexpression rescued the suppression of miR-211/204 in RCC cell proliferation. In short, circMTO1 repressed RCC progression by regulating KLF6 via sponging miR-211 and miR-204, which may provide new idea of diagnosis and treatment in renal cell carcinoma.

Machine learning-based prediction of invisible intraprostatic prostate cancer lesions on 68 Ga-PSMA-11 PET/CT in patients with primary prostate cancer.

PURPOSE: 68 Ga-PSMA PET/CT has high specificity and sensitivity for the detection of both intraprostatic tumor focal lesions and metastasis. However, approximately 10% of primary prostate cancer are invisible on PSMA-PET (exhibit no or minimal uptake). In this work, we investigated whether machine learning-based radiomics models derived from PSMA-PET images could predict invisible intraprostatic lesions on 68 Ga-PSMA-11 PET in patients with primary prostate cancer. METHODS: In this retrospective study, patients with or without prostate cancer who underwent 68 Ga-PSMA PET/CT and presented negative on PSMA-PET image at either of two different institutions were included: institution 1 (between 2017 and 2020) for the training set and institution 2 (between 2019 and 2020) for the external test set. Three random forest (RF) models were built using selected features extracted from standard PET images, delayed PET images, and both standard and delayed PET images. Then, subsequent tenfold cross-validation was performed. In the test phase, the three RF models and PSA density (PSAD, cut-off value: 0.15 ng/ml/ml) were tested with the external test set. The area under the receiver operating characteristic curve (AUC) was calculated for the models and PSAD. The AUCs of the radiomics model and PSAD were compared. RESULTS: A total of 64 patients (39 with prostate cancer and 25 with benign prostate disease) were in the training set, and 36 (21 with prostate cancer and 15 with benign prostate disease) were in the test set. The average AUCs of the three RF models from tenfold cross-validation were 0.87 (95% CI: 0.72, 1.00), 0.86 (95% CI: 0.63, 1.00), and 0.91 (95% CI: 0.69, 1.00), respectively. In the test set, the AUCs of the three trained RF models and PSAD were 0.903 (95% CI: 0.830, 0.975), 0.856 (95% CI: 0.748, 0.964), 0.925 (95% CI:0.838, 1.00), and 0.662 (95% CI: 0.510, 0.813). The AUCs of the three radiomics models were higher than that of PSAD (0.903, 0.856, and 0.925 vs. 0.662, respectively; P = .007, P = .045, and P = .005, respectively). CONCLUSION: Random forest models developed by 68 Ga-PSMA-11 PET-based radiomics features were proven useful for accurate prediction of invisible intraprostatic lesion on 68 Ga-PSMA-11 PET in patients with primary prostate cancer and showed better diagnostic performance compared with PSAD.

The Underlying Molecular Basis and Mechanisms of Venous Thrombosis in Patients with Osteomyelitis: A Data-Driven Analysis.

Objective: Osteomyelitis (OM) is one of the most risky and challenging diseases. Emerging evidence indicates OM is a risk factor for increasing incidence of venous thromboembolism (VTE) development. However, the mechanisms have not been intensively investigated. Methods: The OM-related dataset GSE30119 and VTE-related datasets GSE19151 and GSE48000 were downloaded from the Gene Expression Omnibus (GEO) database and analyzed to identify the differentially expressed genes (DEGs) (OMGs1 and VTEGs1, respectively). Functional enrichment analyses of Gene Ontology (GO) terms were performed. VTEGs2 and OMGs2 sharing the common GO biological process (GO-BP) ontology between OMGs1 and VTEGs1 were detected. The TRRUST database was used to identify the upstream transcription factors (TFs) that regulate VTEGs2 and OMGs2. The protein-protein interaction (PPI) network between VTEGs2 and OMGs2 was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and then visualized in Cytoscape. Topological properties of the PPI network were calculated by NetworkAnalyzer. The Molecular Complex Detection (MCODE) plugin was utilized to perform module analysis and choose the hub modules of the PPI network. Results: A total of 587 OMGs1 and 382 VTEGs1 were identified from the related dataset, respectively. GO-BP terms of OMGs1 and shared DGEs1 were mainly enriched in the neutrophil-related immune response process, and the shared GO-BP terms of OMGs1 and VTEGs1 seemed to be focused on cell activation, immune, defense, and inflammatory response to stress or biotic stimulus. 230 VTEGs2, 333 OMGs2, and 13 shared DEGs2 were detected. 3 TF-target gene pairs (SP1-LSP1, SPI1-FCGR1A, and STAT1-FCGR1A) were identified. The PPI network contained 1611 interactions among 467 nodes. The top 10 hub proteins were TP53, IL4, MPO, ELANE, FOS, CD86, HP, SOCS3, ICAM1, and SNRPG. Several core nodes (such as MPO, ELANE, and CAMP) were essential components of the neutrophil extracellular traps (NETs) network. Conclusion: This is the first data-mining study to explore shared signatures between OM and VTE by the integrated bioinformatic approach, which can help uncover potential biomarkers and therapeutic targets of OM-related VTE.

Inhibition of endoplasmic reticulum stress by 4-phenylbutyrate alleviates retinal inflammation and the apoptosis of retinal ganglion cells after ocular alkali burn in mice.

OBJECTIVE: Retinal ganglion cell (RGC) apoptosis is one of the most severe complications that causes permanent visual impairment following ocular alkali burn (OAB). Currently, very few treatment options exist for this condition. This study was conducted to determine the effect of 4-phenylbutyric acid (4-PBA) on endoplasmic reticulum (ER) stress after OAB using a well-established OAB mouse model. METHODS: Ocular alkali burn was induced in C57BL/6 mouse corneas using 1 M NaOH. 4-PBA (10 mg/kg; 250 µL per injection) or saline (250 µL per injection) was injected intraperitoneally once per day for 3 days before the establishment of the OAB model. The apoptosis of retinal ganglion cells (RGCs) was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and the histological damage was examined by hematoxylin and eosin and immunofluorescence assay on retinal flat mounts. The key inflammatory response and the expression of ER stress-related markers in the retinal tissues were assessed by real-time PCR, western blotting and histologic analyses. RESULTS: 4-PBA significantly alleviated the apoptosis of RGCs and prevented the structural damage of the retina, as determined by the evaluation of RGC density and retinal thickness. Inhibition of ER stress by 4-PBA decreased the expression of vital proinflammatory cytokines, tumor necrosis factor alpha, and interleukin-1 beta; and suppressed the activation of retinal microglial cells and nuclear factor-kappa B (NF-κB). 4-PBA reduced the expression of the ER stress molecules, glucose-regulated protein 78, activated transcription factor 6, inositol-requiring enzyme-1 (IRE1), X-box-binding protein 1 splicing, and CCAAT/enhancer-binding protein homologous protein, in the retinal tissues and RGCs of OAB mice. CONCLUSIONS: The present study demonstrated that the inhibition of ER stress by 4-PBA alleviates the inflammatory response via the IRE1/NF-κB signaling pathway and protects the retina and RGCs from injury in an OAB mouse model. Such findings further suggest that 4-PBA might have potential therapeutic implications for OAB treatment.

Autologous Cultured Bone Marrow-Derived Mesenchymal Stem Cells in a Fibrin Spray to Treat Venous Ulcers: A Randomized Controlled Double-Blind Pilot Study.

We treated a small cohort of venous ulcers that were very unresponsive to standard and advanced therapies with autologous cultured bone marrow-derived mesenchymal stem cells (MSCs). This pilot clinical trial was randomized, controlled, and double-blinded. Subjects were treated with either normal saline (Group A), fibrin spray alone (Group B), or MSCs in fibrin (1 million cells/cm2 of wound bed surface) (Group C). The control and test materials were applied to the wound using a double-barreled syringe with thrombin and fibrinogen (with or without MSCs) in each barrel, or saline alone in both barrels. The MSCs were separated, cultured in vitro, and expanded in a dedicated Good Manufacturing Practice (GMP) facility from 30-50 ml of bone marrow aspirate obtained from the iliac crest in Group C subjects. To ensure that the study remained controlled and blinded, subjects who were randomized to one of the two control arms (saline or fibrin) underwent sham bone marrow aspiration performed by a hematologist who anesthetized the iliac crest area down to and pushing against the periosteum, but without penetrating the bone marrow. Therefore, both the clinician who evaluated wound progress and the study subjects had no knowledge of whether bone aspiration was actually performed and what treatment had been applied to the wound. The study was performed after full FDA investigational new drug (IND) approval. The primary endpoint was the rate of healing (wound closure as linear healing from the wound margins in cm/week), as measured by the Gilman equation. One-way ANOVA was used to calculate the statistical significance of differences between the mean healing rates of each of the 3 treatment groups every 4 weeks and over the 24 weeks of treatment. Overall, treatment with MSCs accelerated the healing rate by about 10-fold compared to those in the saline and fibrin control groups. Although the total number of patients in this pilot study was small (n=11), the statistical significance was surprisingly promising: p<0.01 and f-ratio of 15.9358. No serious adverse events were noted. This small but carefully performed prospective, controlled, randomized, and double-blinded pilot study in a rare population of totally unresponsive patients adds to previous reports showing the promise of MSCs in the treatment of chronic wounds and provides proof of principle for how to approach this type of very demanding clinical and translational research.

Effect of Tauroursodeoxycholic Acid on Inflammation after Ocular Alkali Burn.

Inflammation is the main cause of corneal and retinal damage in an ocular alkali burn (OAB). The aim of this study was to investigate the effect of tauroursodeoxycholic acid (TUDCA) on ocular inflammation in a mouse model of an OAB. An OAB was induced in C57BL/6j mouse corneas by using 1 M NaOH. TUDCA (400 mg/kg) or PBS was injected intraperitoneally (IP) once a day for 3 days prior to establishing the OAB model. A single injection of Infliximab (6.25 mg/kg) was administered IP immediately after the OAB. The TUDCA suppressed the infiltration of the CD45-positive cells and decreased the mRNA and protein levels of the upregulated TNF-α and IL-1ß in the cornea and retina of the OAB. Furthermore, the TUDCA treatment inhibited the retinal glial activation after an OAB. The TUDCA treatment not only ameliorated CNV and promoted corneal re-epithelization but also attenuated the RGC apoptosis and preserved the retinal structure after the OAB. Finally, the TUDCA reduced the expression of the endoplasmic reticulum (ER) stress molecules, IRE1, GRP78 and CHOP, in the retinal tissues of the OAB mice. The present study demonstrated that the TUDCA inhibits ocular inflammation and protects the cornea and retina from injury in an OAB mouse model. These results provide a potential therapeutic intervention for the treatment of an OAB.

Th17 Activation and Th17/Treg Imbalance in Prolonged Anterior Intraocular Inflammation after Ocular Alkali Burn.

Ocular alkali burn (OAB) is a sight-threatening disease with refractory ocular inflammation causing various blinding complications. Th17 lymphocytes account for the pathogeneses of the autoimmune disease and chronic inflammation, but their role in prolonged anterior intraocular inflammation after OAB is still unknown. A rat OAB model was established for this purpose. Anterior intraocular inflammation was observed in both the acute and late phases of OAB, and histological examination confirmed the presence of inflammatory cell infiltration and fibrin exudation in the anterior segment. Luminex xMAP technology and qPCR were used to evaluate the intraocular levels of cytokines. The levels of IL-1ß, IL-6, and TNF-α were significantly elevated during the acute phase. The expression of IL-17A gradually increased from day 7 onwards and remained at a relatively high level. Immunofluorescence was performed to identify Th17 cells. CD4 and IL-17A double positive cells were detected in the anterior chamber from days 7 to 28. Flow cytometry showed that the frequency of Th17 cells increased in both lymph nodes and spleen, while the frequency of Treg cells remained unchanged, resulting in an elevated Th17/Treg ratio. The present study suggests that Th17 activation and Th17/Treg imbalance account for prolonged anterior intraocular inflammation after OAB.

METTL3 attenuates proliferative vitreoretinopathy and epithelial-mesenchymal transition of retinal pigment epithelial cells via wnt/ß-catenin pathway.

Proliferative vitreoretinopathy (PVR) is a refractory vitreoretinal fibrosis disease, and epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is the key pathological mechanism of PVR. However, few studies focused on the role of METTL3, the dominating methyltransferase for m6A RNA modification in PVR pathogenesis. Immunofluorescence staining and qRT-PCR were used to determine the expression of METTL3 in human tissues. Lentiviral transfection was used to stably overexpress and knockdown METTL3 in ARPE-19 cells. MTT assay was employed to study the effects of METTL3 on cell proliferation. The impact of METTL3 on the EMT of ARPE-19 cells was assessed by migratory assay, morphological observation and expression of EMT markers. Intravitreal injection of cells overexpressing METTL3 was used to assess the impact of METTL3 on the establishment of the PVR model. We found that METTL3 expression was less in human PVR membranes than in the normal RPE layers. In ARPE-19 cells, total m6A abundance and the METTL3 expression were down-regulated after EMT. Additionally, METTL3 overexpression inhibited cell proliferation through inducing cell cycle arrest at G0/G1 phase. Furthermore, METTL3 overexpression weakened the capacity of TGFß1 to trigger EMT by regulating wnt/ß -catenin pathway. Oppositely, knockdown of METTL3 facilitated proliferation and EMT of ARPE-19 cells. In vivo, intravitreal injection of METTL3-overexpressing cells delayed the development of PVR compared with injection of control cells. In summary, this study suggested that METTL3 is involved in the PVR process, and METTL3 overexpression inhibits the EMT of ARPE-19 cells in vitro and suppresses the PVR process in vivo.

Etiology, microbiological isolates, and antibiotic susceptibilities in culture-proven pediatric endophthalmitis: a 9-year review.

PURPOSE: To analyze the etiology, microbiological isolates, and antibiotic susceptibilities of endophthalmitis in pediatric patients. METHODS: Patients aged < 18 years with culture-positive endophthalmitis in Zhongshan Ophthalmic Center between January 2010 and December 2018 were included retrospectively. RESULTS: A total of 127 patients (127 eyes) were included, and 108 (85%) had posttraumatic endophthalmitis. Streptococcus (21.4%), coagulase-negative Staphylococcus (14.5%), Aspergillus (6.9%), and Bacillus cereus (5.3%) were the common organisms. The proportion of Streptococcus decreased with age (40.0% in 0-3 years, 16.3% in 4-12 years, and 6.3% in 13-17 years), while coagulase-negative Staphylococcus increased from 5.7% to 18.8%. Overall, fluoroquinolones achieved the highest antibiotic susceptibility rate (> 95%), while the susceptibility of isolated bacteria to tobramycin and cefazolin was only 60.2% and 59.4%, respectively. The susceptibility rates of Gram-positive cocci to cephalosporins were nearly 90%. For Gram-negative bacilli, susceptibility to neomycin was 91.3%. CONCLUSION: Trauma was the main etiology for pediatric endophthalmitis. Although Streptococcus was the most prevalent organism in general, the dominant pathogen varied with age, which merits clinical attention. Fluoroquinolones showed the highest antibiotic efficacy; however, commonly used antibiotics tobramycin and cefazolin showed relatively low antibiotic susceptibility. Thus, antibiotic resistance in pediatric populations merits clinical attention.

The retinal vasculature pathophysiological changes in vision recovery after treatment for indirect traumatic optic neuropathy patients.

PURPOSE: To evaluate the retinal vasculature pathophysiological changes of indirect traumatic optic neuropathy (ITON) patients after effective surgery. METHODS: Monocular ITON patients who underwent endoscopic trans-ethmosphenoid optic canal decompression (ETOCD) or conservative treatments in Zhongshan Ophthalmic Center from January 2017 to June 2020 were recruited. Visual acuity (VA), visual evoked potential (VEP), oxygen saturation of retinal blood vessels (SO2), and optical coherence tomography angiography (OCT-A) were measured. All patients were followed up at least 3 months after treatments. RESULTS: A total of 95 ITON patients were recruited, including 77 patients who underwent ETOCD and 18 patients who underwent conservative treatments. After treatments, more patients received ETOCD (59/77 = 76.6%) presented with improved VA compared with the patients with conservative treatments (6/18 = 33.3%). Compared with the pre-therapeutic measurements, VEP were significantly improved after surgery in ETOCD-treated patients (P < 0.05). Latent periods of P1 and N2, as well as amplitude of P2 of VEP parameters, showed more sensitive to vision recovery (P < 0.05). Retinal artery SO2 and the differences between arteries and veins were improved in ETOCD-treated patients (P < 0.05). Meanwhile, with OCT-A examination, the retinal thickness and retinal vessel density were notably better in ETOCD-treated patients after surgery than that in patients received conservative treatments (P < 0.05). CONCLUSIONS: Vision recovery after effective treatment of ITON patients was associated with the increased oxygen saturation of retinal vessels, better availability of oxygen in the retina, greater vessel density, and thicker retinas, which might further underlie the vasculature mechanism of vision recovery in ITON patients.

Risk Factors and Prognosis of Pediatric Open Globe Injuries without Initial Light Perception.

PURPOSE: The aim of this study was to investigate the possible risk factors and prognosis of initial no light perception (NLP) in pediatric open globe injuries (POGI). PROCEDURES: This retrospective, comparative, interventional case-control study included 865 eyes of POGI patients presenting to a tertiary referral ophthalmic center from January 1, 2011 to December 31, 2015. Eyes were divided into 2 groups: the NLP group included eyes with initial NLP, and the light perception (LP) group included eyes with initial LP or vision better than LP. RESULTS: The following risk factors were significantly related to initial NLP: severe intraocular hemorrhage (OR 3.287, p = 0.015), retinal detachment (RD; OR 2.527, p = 0.007), choroidal damage (OR 2.680, p = 0.016), and endophthalmitis (OR 4.221, p < 0.001). Choroidal damage is related to remaining NLP after vitreoretinal surgery (OR 12.384, p = 0.003). At the last visit, more eyes in the NLP group suffered from silicone oil-sustained status (OR 0.266, p = 0.020) or ocular atrophy (OR 0.640, p = 0.004), and fewer eyes benefitted from final LP (OR 41.061, p < 0.001) and anatomic success (OR 4.515, p < 0.001). CONCLUSION: Severe intraocular hemorrhage, RD, choroidal damage, and endophthalmitis were possible predictors of initial NLP in POGI. Choroidal damage was the major factor related to an NLP prognosis. Traumatized eyes with initial NLP could be anatomically and functionally preserved by vitreoretinal surgery.

Dermal Fibroblasts from Chronic Wounds Exhibit Paradoxically Enhanced Proliferative and Migratory Activities that May be Related to the Non-Canonical Wnt Signaling Pathway.

It is generally thought that dermal fibroblasts from chronic wounds are in a state of senescence, which contributes to the failure to heal. This assumption, based on limited experimental evidence, has led to the widespread use of therapeutic approaches focused on delivering new fibroblasts and/or increasing resident fibroblast activity to promote healing. In this study, we decided to re-visit the evidence for the relative inactivity of resident chronic wound fibroblasts. We therefore evaluated the proliferative and migratory activities of matching, patient-derived dermal fibroblasts from a chronic wound (wound dermal fibroblasts, or WDF), ipsilateral thigh newly created acute wound dermal fibroblasts (ADF, Day-3 after wounding the normal thigh skin), and ipsilateral thigh normal dermal skin fibroblasts (NDF). This approach was used in each of 10 consecutive non-selected individual patients with a venous leg ulcer, and allowed us to determine whether WDF are intrinsically less active than NDF and AWD. Cell migration and proliferation were quantified by a live-cell analysis system and MTT assay, respectively, in low (0.5%) or high (10%) levels of fetal bovine serum (FBS). In addition, the ability of patient-derived fibroblasts to modulate wound re-epithelialization in vivo was analyzed by transplantation in a mouse tail full-thickness wound model. Wnt5a mRNA, its ROR1 co-receptors, and ROR2 mRNA levels were determined by qRT-PCR. We report that WDF had increased -SMA and increased levels of Wnt5a. Moreover, using live-cell imaging in a scratch assay monolayer model, WDF showed baseline migratory activity similar to those of NDF and ADF, and such activity was not stimulated by FBS. WDF showed the same capacity to increase wound re-epithelialization as NDF and ADF. Together, these results suggest that WDF are not actually less "active" than NDF and ADF. This enhanced activity of chronic wound fibroblasts may lead to high energy requirements that contribute to a failure to heal. The findings may represent a new paradigm for wound chronicity, impaired healing, and high recurrence rates.

Development of a rabbit model of persistent hypotony without ciliary body injury.

In order to study the pathophysiological alterations of the ciliary body (CB) during persistent hypotony, it is necessary to develop an animal model without CB injury. In this study, we successfully established a modified model of persistent hypotony without CB injury in New Zealand rabbits. A 23-gauge pars plana vitrectomy (PPV) was performed and a trocar-formed fistula was allowed to remain in situ, to produce a continuous outflow of intraocular fluid. Both eyes underwent PPV with normal intraocular pressure (IOP); eyes with no surgical intervention were used as controls. The IOP was monitored and used to evaluate the reliability of the model. Secondary changes of hypotony were evaluated by slit-lamp biomicroscopy and B scans while morphological changes of the CB were observed by haematoxylin and eosin staining. The mean IOP in the hypotony groups were consistently lower than 6 mmHg. Furthermore, there were no significant differences in IOP between the PPV control group and normal eyes. Collectively, our data indicate that this model successfully simulates the secondary changes of hypotony, including a reduction in corneal size, corneal oedema, anterior chamber inflammation, morphological alterations of the CB, cataract, retinal detachment, and choroidal detachment. The morphological structure of the CB tissue changed dramatically after persistent hypotony, indicating that normal IOP may be required in order to maintain normal function in the CB. This model of persistent hypotony potentially represents a valuable tool for future studies aiming to investigate the pathophysiological mechanisms underlying CB dysfunction and other secondary changes that occur during hypotony.