Context-aware learning for cancer cell nucleus recognition in pathology images.

MOTIVATION: Nucleus identification supports many quantitative analysis studies that rely on nuclei positions or categories. Contextual information in pathology images refers to information near the to-be-recognized cell, which can be very helpful for nucleus subtyping. Current CNN-based methods do not explicitly encode contextual information within the input images and point annotations. RESULTS: In this article, we propose a novel framework with context to locate and classify nuclei in microscopy image data. Specifically, first we use state-of-the-art network architectures to extract multi-scale feature representations from multi-field-of-view, multi-resolution input images and then conduct feature aggregation on-the-fly with stacked convolutional operations. Then, two auxiliary tasks are added to the model to effectively utilize the contextual information. One for predicting the frequencies of nuclei, and the other for extracting the regional distribution information of the same kind of nuclei. The entire framework is trained in an end-to-end, pixel-to-pixel fashion. We evaluate our method on two histopathological image datasets with different tissue and stain preparations, and experimental results demonstrate that our method outperforms other recent state-of-the-art models in nucleus identification. AVAILABILITY AND IMPLEMENTATION: The source code of our method is freely available at https://github.com/qjxjy123/DonRabbit. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Clinical, radiographic characterizations and complications of maxillary molar in a periodontitis population: a retrospective study based on CBCT radiography.

OBJECTIVE: This study was aimed to delineate the clinical, CBCT radiographic characteristics, and complications of maxillary molar in a periodontitis population. MATERIALS AND METHODS: Medical records and CBCT images were utilized to identify adult patients with periodontitis in a tertiary referral dental hospital between June 2019 and December 2020. CBCT scan images were used to characterize the detailed bone thickness, absorbing height, and position of maxillary molar as well as their associated conditions. All relevant descriptive epidemiological data, clinical information, radiographic details, and associated complications were recorded and statistically analyzed. RESULTS: According to the above criteria, 577 eligible periodontitis patients were enrolled and defined as research cohort here with mean age 45 ± 4.8 years. Male patients outnumbered females with a gender ratio of 1.23:1. Our results demonstrated that the bone loss of maxillary first molar was more serious than that of second molar with tooth position symmetry. The occurrence of various complications (periodontal abscess, pulp lesions, furcation lesion, and mucosal thickening) was significantly correlated to periodontal-related clinical parameters of maxillary molar. CONCLUSIONS: Our results demonstrated the more serious bone loss of maxillary first molar with tooth position symmetry. The occurrence of various complications was significantly correlated to periodontal-related clinical parameters. Our findings offer valuable information concerning the clinical, radiographic characteristics, and complications of maxillary molar in a periodontitis population. CLINICAL RELEVANCE: These findings are beneficial for clinicians to comprehensively understand the bone status, pathogenesis, and clinical management of maxillary molar in periodontitis.

Antimicrobial activity against Staphylococcus aureus and genome features of Lactiplantibacillus plantarum LR-14 from Sichuan pickles.

The persistence of Staphylococcus aureus within biofilm can lead to contamination of medical devices and life-threatening infections. Luckily, lactic acid bacteria (LAB) have an inhibitory effect on the growth of these bacteria. This study aims to select LAB strains from fermented vegetables, and analyze their potential inhibition activities against S. aureus. In total, 45 isolates of LAB were successfully isolated from Sichuan pickles, and the CFS of Lactiplantibacillus plantarum LR-14 exerted the strongest inhibitory effect against S. aureus. Moreover, S. aureus cells in planktonic and biofilm states both wrinkled and damaged when treated with the CFS of L. plantarum LR-14. In addition, whole genome sequencing analysis indicates that L. plantarum LR-14 contains various functional genes, including predicted extracellular polysaccharides (EPS) biosynthesis genes, and genes participating in the synthesis and metabolism of fatty acid, implying that L. plantarum LR-14 has the potential to be used as a probiotic with multiple functions.

Gas Sensors Based on Single-Wall Carbon Nanotubes.

Single-wall carbon nanotubes (SWCNTs) have a high aspect ratio, large surface area, good stability and unique metallic or semiconducting electrical conductivity, they are therefore considered a promising candidate for the fabrication of flexible gas sensors that are expected to be used in the Internet of Things and various portable and wearable electronics. In this review, we first introduce the sensing mechanism of SWCNTs and the typical structure and key parameters of SWCNT-based gas sensors. We then summarize research progress on the design, fabrication, and performance of SWCNT-based gas sensors. Finally, the principles and possible approaches to further improving the performance of SWCNT-based gas sensors are discussed.

Rho-GEF trio regulates osteoclast differentiation and function by Rac1/Cdc42.

Many bone diseases result from abnormal bone resorption by osteoclasts (OCs). Studying OC related regulatory genes is necessary for the development of new therapeutic strategies. Rho GTPases have been proven to regulate OC differentiation and function and only mature OCs can carry out bone resorption. Here we demonstrate that Rac1 and Cdc42 exchange factor Triple functional domain (Trio) is critical for bone resorption caused by OCs. In this study, we created LysM-Cre;Triofl/fl conditional knockout mice in which Trio was conditionally ablated in monocytes. LysM-Cre;Triofl/fl mice showed increased bone mass due to impaired bone resorption caused by OCs. Furthermore, our in vitro analysis indicated that Trio conditional deficiency significantly suppressed OC differentiation and function. At the molecular level, Trio deficiency significantly inhibited the expression of genes critical for osteoclastogenesis and OC function. Mechanistically, our researches suggested that perturbed Rac1/Cdc42-PAK1-ERK/p38 signaling could be used to explain the lower ability of bone resorption in CKO mice. Taken together, this study indicates that Trio is a regulator of OCs. Studying the role of Trio in OCs provides a potential new insight for the treatment of OC related bone diseases.

Pax2 is essential for proliferation and osteogenic differentiation of mouse mesenchymal stem cells via Runx2.

Mesenchymal stem cells (MSCs) have been widely studied in the field of regenerative medicine with the potential to solve osteoporosis. Paired box 2 (Pax2), as a transcription factor, is the master regulator of embryogenesis and oncogenesis. However, the function of Pax2 in osteogenesis is unknown. Here, we reported for the first time that the expression of Pax2 gradually increased during osteogenic differentiation of mouse MSCs, and osteoprogenitor cells. However, detected in osteoblastic cells of mouse tibia, the expression of Pax2 in the embryonic stage was higher than that in adulthood. In C3H/10/T1/2 cells and compact bone-derived mouse MSCs (mMSCs), Pax2 knock-down inhibited the proliferation of these cells, down-regulated the expression of osteogenic marker genes, as well as repressed the ALP activity and mineralization. In addition, Pax2 enhanced the transcriptional activity of Runx2, and activated the MAPK pathway genes (ERK, JNK and p38). Furthermore, knock-down of Pax2 repressed the mMSCs-mediated bone regeneration in an ectopic bone formation model. In conclusion, Pax2 promotes osteogenesis of mouse MSCs, suggesting that Pax2 has a role in the pathophysiology of bone related diseases, and has potential application in bone tissue regeneration.

The role of Rho-GEF Trio in regulating tooth root development through the p38 MAPK pathway.

Trio, the Rho guanine nucleotide exchange factor (Rho-GEF), plays diverse roles in cell migration, cell axon guidance and cytoskeleton reorganization. Conserved during evolution, Trio encodes two guanine nucleotide exchange factor domains (GEFs) and activates small GTPases. The Rho-family small GTPases RhoA and Rac1, which are target molecules of Trio, have been described to engage in craniofacial development and tooth formation. However, the exact role of Trio in tooth development remains elusive. In this study, we generated Wnt1-cre;Triofl/fl mice to address the potential function of Trio in tooth development. Wnt1-cre;Triofl/fl mice showed short root deformity as well as decreased expression of odontogenic makers such as RUNX2, OSX, OCN, and OPN. In vitro, Trio was silenced in human stem cells of dental papilla (SCAPs). Compared with the control group, the proliferation and migration ability in the experimental group was disrupted. After knocking down Trio in SCAPs, the cells showed phenotypes of poor odontogenic differentiation and weak mineralized nodules. To study the underlying mechanism, we investigated the p38 MAPK pathway and found that loss of Trio blocked the cascade transduction of p38 MAPK signaling. In conclusion, we identified Trio as a novel coordinator in regulating root development and clarified its relevant molecular events.

High-Performance Materials Improve the Early Shrinkage, Early Cracking, Strength, Impermeability, and Microstructure of Manufactured Sand Concrete.

The poor early shrinkage and cracking performances of manufactured sand concrete, waste powder concrete, and recycled aggregate concrete are the main difficulties in engineering applications. To solve these problems, early shrinkage and cracking, strength, and impermeability tests were performed on high-volume stone powder manufactured sand concrete mixed with fly ash and slag powder (FS), a shrinkage-reducing agent (SRA), polyvinyl alcohol (PVA) fibers, and a superabsorbent polymer (SAP). Furthermore, the microstructures and pore structures of these concretes were revealed using nuclear magnetic resonance (NMR) and scanning electron microscopy (SEM). The results showed that the mixture of FS, SRA, PVA fibers, and SAP could effectively inhibit the shrinkage strain and cracking area of the concrete. The effect of the SAP on reducing the early shrinkage of the concrete is the greatest, and the shrinkage strain can be reduced by 76.49%. The PVA fibers had the most obvious effect on inhibiting the early cracking of the concrete, and the total cracking area was reduced by 66.91%. Significantly, the incorporation of the FS can improve the particle gradation and the pore structure and improve its compactness. The PVA fibers not only provide good carriers for cement-based materials but also enhance the bonding force between the particles inside the concrete, filling the pores inside the concrete, inhibiting the loss of water, and reducing the generation of internal microcracks. The FS and PVA can reduce the shrinkage and cracking risk and improve the strength and impermeability of the concrete. Although the SRA and SAP can reduce the shrinkage and cracking risks, it will lead to a significant decrease in the later strength and impermeability. The main reason is that the SRA leads to an increase in micropores in the matrix and microcracks near the aggregate, which are not conducive to the development of the strength and penetration resistance of the MS. Similarly, the SAP can promote the rapid formation of ettringite (Aft) at an early age and improve the early shrinkage, early cracking, and early strength of the concrete. However, with an increase in age, the residual pores, after SAP dehydration, will cause the deterioration of the concrete pore structure, resulting in the deterioration of the strength and impermeability.

RtNAC055 promotes drought tolerance via a stomatal closure pathway linked to methyl jasmonate/hydrogen peroxide signaling in Reaumuria trigyna.

The stomata regulate CO2 uptake and efficient water usage, thereby promoting drought stress tolerance. NAC proteins (NAM, ATAF1/2, and CUC2) participate in plant reactions following drought stress, but the molecular mechanisms underlying NAC-mediated regulation of stomatal movement are unclear. In this study, a novel NAC gene from Reaumuria trigyna, RtNAC055, was found to enhance drought tolerance via a stomatal closure pathway. It was regulated by RtMYC2 and integrated with jasmonic acid signaling and was predominantly expressed in stomata and root. The suppression of RtNAC055 could improve jasmonic acid and H2O2 production and increase the drought tolerance of transgenic R. trigyna callus. Ectopic expression of RtNAC055 in the Arabidopsis atnac055 mutant rescued its drought-sensitive phenotype by decreasing stomatal aperture. Under drought stress, overexpression of RtNAC055 in poplar promoted ROS (H2O2) accumulation in stomata, which accelerated stomatal closure and maintained a high photosynthetic rate. Drought upregulated the expression of PtRbohD/F, PtP5CS2, and PtDREB1.1, as well as antioxidant enzyme activities in heterologous expression poplars. RtNAC055 promoted H2O2 production in guard cells by directly binding to the promoter of RtRbohE, thus regulating stomatal closure. The stress-related genes RtDREB1.1/P5CS1 were directly regulated by RtNAC055. These results indicate that RtNAC055 regulates stomatal closure by maintaining the balance between the antioxidant system and H2O2 level, reducing the transpiration rate and water loss, and improving photosynthetic efficiency and drought resistance.

The role of globular heads of the C1q receptor in HPV 16 E2-induced human cervical squamous carcinoma cell apoptosis is associated with p38 MAPK/JNK activation.

BACKGROUND: Human papillomavirus type 16 (HPV 16) E2 protein is a multifunctional DNA-binding protein. HPV 16 E2 regulates many biological responses, including DNA replication, gene expression, and apoptosis. The purpose of this study was to investigate the relationship among the receptor for globular heads of the human C1q (gC1qR) gene expression, HPV 16 E2 transfection and apoptosis regulation in human cervical squamous carcinoma cells (C33a and SiHa). METHODS: gC1qR expression was examined in C33a and SiHa cells using real-time PCR and Western blot analysis. Apoptosis of C33a and SiHa cells was assessed by flow cytometry. C33a and SiHa cell viability, migration and proliferation were detected using the water-soluble tetrazolium salt (WST-1) assay, a transwell assay and 3H-thymidine incorporation into DNA (3H-TdR), respectively. RESULTS: C33a and SiHa cells that were transfected with a vector encoding HPV 16 E2 displayed significantly increased gC1qR gene expression and p38 mitogen-activated protein kinase (p38 MAPK)/c-jun N-terminal kinase (JNK) activation as well as up-regulation of cellular apoptosis, which was abrogated by the addition of gC1qR small interfering RNA (siRNA). Furthermore, the changes in C33a and SiHa cell viability, migration and proliferation that were observed upon HPV 16 E2 transfection were abrogated by SB203580 (a p38 MAPK inhibitor) or SP600125 (a JNK inhibitor) treatment. CONCLUSION: These data support a mechanism whereby HPV 16 E2 induces apoptosis by silencing the gC1qR gene or inhibiting p38 MAPK/JNK signalling in cervical squamous cell carcinoma.

Enrichment of Large-Diameter Semiconducting Single-Walled Carbon Nanotubes by Conjugated Polymer-Assisted Separation.

Semiconducting single-walled carbon nanotubes (s-SWCNTs) with large diameters are highly desired in the construction of high performance optoelectronic devices. However, it is difficult to selectively prepare large-diameter s-SWCNTs since their structure and chemical stability are quite similar with their metallic counterparts. In this work, we use SWCNTs with large diameter as a raw material, conjugated polymer of regioregular poly-(3-dodecylthiophene) (rr-P3DDT) with long side chain as a wrapping agent to selectively separate large-diameter s-SWCNTs. It is found that s-SWCNTs with a diameter of ~1.9 nm are effectively enriched, which shows a clean surface. By using the sorted s-SWCNTs as a channel material, we constructed thin-film transistors showing charge-carrier mobilities higher than 10 cm2 V-1 s-1 and on/off ratios higher than 103.

Oral pathogen aggravates atherosclerosis by inducing smooth muscle cell apoptosis and repressing macrophage efferocytosis.

Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen, particularly the Porphyromonas gingivalis (P. gingivalis), by inducing apoptosis. However, it remains obscure whether accumulated apoptotic cells in P. gingivalis-accelerated plaque formation are associated with impaired macrophage clearance. Here, we show that smooth muscle cells (SMCs) have a greater susceptibility to P. gingivalis-induced apoptosis than endothelial cells through TLR2 pathway activation. Meanwhile, large amounts of miR-143/145 in P.gingivalis-infected SMCs are extracellularly released and captured by macrophages. Then, these miR-143/145 are translocated into the nucleus to promote Siglec-G transcription, which represses macrophage efferocytosis. By constructing three genetic mouse models, we further confirm the in vivo roles of TLR2 and miR-143/145 in P. gingivalis-accelerated atherosclerosis. Therapeutically, we develop P.gingivalis-pretreated macrophage membranes to coat metronidazole and anti-Siglec-G antibodies for treating atherosclerosis and periodontitis simultaneously. Our findings extend the knowledge of the mechanism and therapeutic strategy in oral pathogen-associated systemic diseases.

Macrophage MVP regulates fracture repair by promoting M2 polarization via JAK2-STAT6 pathway.

OBJECTIVE: Major vault protein (MVP) is vital in various macrophage-related inflammatory diseases. However, the effects of MVP on macrophage polarization during fracture repair are still unknown. METHODS: We used Mvpflox/floxLyz2-Cre mice (myeloid-specific MVP gene knockout, abbreviated as MacKO) and Mvpflox/flox (abbreviated as MacWT) mice to compare their fracture healing phenotype. Next, we traced the changes in macrophage immune status in vivo and in vitro. We further explored the effects of MVP on osteogenesis and osteoclastogenesis. Finally, we re-expressed MVP in MacKO mice to confirm the role of MVP in fracture healing. RESULTS: The lack of MVP in macrophages impaired their transition from a pro-inflammatory to an anti-inflammatory phenotype during fracture repair. The increased secretion of pro-inflammatory cytokines by macrophages promoted their osteoclastic differentiation and impaired BMSC osteogenic differentiation, ultimately leading to impaired fracture repair in MacKO mice. Last, adeno-associated virus (AAV)-Mvp tibial injection significantly promoted fracture repair in MacKO mice. CONCLUSIONS: Our findings showed MVP has a previously unknown immunomodulatory role in macrophages during fracture repair. Targeting macrophage MVP may represent a novel therapeutic method for fracture treatment.

Multiplexed Genome Editing for Efficient Phenotypic Screening in Zebrafish.

Zebrafish are widely used to investigate candidate genes for human diseases. While the emergence of CRISPR-Cas9 technology has revolutionized gene editing, the use of individual guide RNAs limits the efficiency and application of this technology in functional genetics research. Multiplexed genome editing significantly enhances the efficiency and scope of gene editing. Herein, we describe an efficient multiplexed genome editing strategy to generate zebrafish mutants. Following behavioural tests and histological examination, we identified one new candidate gene (tmem183a) for hearing loss. This study provides a robust genetic platform to quickly obtain zebrafish mutants and to identify candidate genes by phenotypic readouts.

Semi-Supervised Cell Detection with Reliable Pseudo-Labels.

Pathological images play an important role in the diagnosis, treatment, and prognosis of cancer. Usually, pathological images contain complex environments and cells of different shapes. Pathologists consume a lot of time and labor costs when analyzing and discriminating the cells in the images. Therefore, fully annotated pathological image data sets are not easy to obtain. In view of the problem of insufficient labeled data, we input a large number of unlabeled images into the pretrained model to generate accurate pseudo-labels. In this article, we propose two methods to improve the quality of pseudo-labels, namely, the pseudo-labeling based on adaptive threshold and the pseudo-labeling based on cell count. These two pseudo-labeling methods take into account the distribution of cells in different pathological images when removing background noise, and ensure that accurate pseudo-labels are generated for each unlabeled image. Meanwhile, when pseudo-labels are used for model retraining, we perform data distillation on the feature maps of unlabeled images through an attention mechanism, which further improves the quality of training data. In addition, we also propose a multi-task learning model, which learns the cell detection task and the cell count task simultaneously, and improves the performance of cell detection through feature sharing. We verified the above methods on three different data sets, and the results show that the detection effect of the model with a large number of unlabeled images involved in retraining is improved by 9%-13% compared with the model that only uses a small number of labeled images for pretraining. Moreover, our methods have good applicability on the three data sets.

Bioimmobilization of lead in phosphate mining wasteland by isolated strain Citrobacter farmeri CFI-01.

Industrial phosphate rock (PR) treatment has introduced lead (Pb) contamination into phosphate mining wasteland, causing serious contamination. Although bioremediation is considered an effective method and studies have investigated the bioimmobilization of Pb contamination in phosphate mining wasteland by phosphate-solubilizing bacteria (PSB), the bioimmobilization mechanism remains unclear. In this study, a strain Citrobacter farmeri CFI-01 with phosphate-solubilizing and Pb-tolerant abilities was isolated from a phosphate mining wasteland. Liquid culture experiments showed that the maximum content of soluble phosphate and the percentage amount of Pb immobilized after 14 days were 351.5 mg/L and 98.18%, respectively, with a decrease in pH. Soil experiments showed that CFI-01 had reasonable bioimmobilization ability, and the percentage amount of Pb immobilized was increased by 7.790% and 22.18% in the groups inoculated with CFI-01, respectively, compared with that of the groups not inoculated with CFI-01. Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM) analyses showed that the immobilization of Pb was also ascribed to changes in the functional groups (e.g., hydroxyl and carboxyl groups) and the formation of lead phosphate sediments. Finally, the results of the metagenomic analysis indicated that changes in the microbial community structure, enrichment of related functional abundances (e.g., metal metabolism, carbohydrate metabolism, and amino acid metabolism functions), and activation of functional genes (e.g., zntA, smtB, cadC, ATOX1, smtA, and ATX1) could help immobilize soil Pb contamination and explore the mechanism of bacterial bioimmobilization in Pb-contaminated soil. This study provides insights for exploring the immobilization mechanism of Pb contamination in phosphate mining wasteland using PSB, which has significance for further research.

Kiaa1024L/Minar2 is essential for hearing by regulating cholesterol distribution in hair bundles.

Unbiased genetic screens implicated a number of uncharacterized genes in hearing loss, suggesting some biological processes required for auditory function remain unexplored. Loss of Kiaa1024L/Minar2, a previously understudied gene, caused deafness in mice, but how it functioned in the hearing was unclear. Here, we show that disruption of kiaa1024L/minar2 causes hearing loss in the zebrafish. Defects in mechanotransduction, longer and thinner hair bundles, and enlarged apical lysosomes in hair cells are observed in the kiaa1024L/minar2 mutant. In cultured cells, Kiaa1024L/Minar2 is mainly localized to lysosomes, and its overexpression recruits cholesterol and increases cholesterol labeling. Strikingly, cholesterol is highly enriched in the hair bundle membrane, and loss of kiaa1024L/minar2 reduces cholesterol localization to the hair bundles. Lowering cholesterol levels aggravates, while increasing cholesterol levels rescues the hair cell defects in the kiaa1024L/minar2 mutant. Therefore, cholesterol plays an essential role in hair bundles, and Kiaa1024L/Minar2 regulates cholesterol distribution and homeostasis to ensure normal hearing.

Cholesterol is present in every cell of the body. While it is best known for its role in heart health, it also plays a major role in hearing, with changes in cholesterol levels negatively affecting this sense. To convert sound waves into electrical brain signals, specialised ear cells rely on hair-like structures which can move with vibrations; cholesterol is present within these hair 'bundles', but its exact role remains unknown. Genetic studies have identified over 120 genes essential for normal hearing. Animal data suggest there may be many more ­ including, potentially, some which control cholesterol. For instance, in mice, loss of the Minar2 gene causes profound deafness. Yet exactly which role the protein that Minar2 codes for plays in the ear remains unknown. This is in part because that protein does not resemble any other related proteins, making it difficult to infer its function. To find out more, Gao et al. investigated loss of minar2 in zebrafish, showing that deleting the gene induced deafness in the animals. Without minar2, the hair bundles in ear cells were longer, thinner, and less able to sense vibrations: cholesterol could not move into these structures, causing them to dysfunction. Exposing the animals to drugs that lower or raise cholesterol levels respectively worsened or improved their hearing abilities. A recent study revealed that mutations in MINAR2 also cause deafness in humans. The findings by Gao et al. highlight the need for further research which explores the role of cholesterol and MINAR2 in hair bundle function, as this may potentially uncover cholesterol-based treatments for hearing problems.

Exosomes in cancer immunoediting and immunotherapy.

As an important means of communication among cells, exosomes are being studied more and more widely, especially in the context of cancer immunotherapy. In the phase of tumor immunoediting, exosomes derived from tumor cells and different immune cells have complex and changeable physiological functions, because they carry different proteins and nucleic acid from the source cells. Based on the role of exosomes in the communication between different cells, cancer treatment methods are also under continuous research. This review briefly introduces the molecular composition of exosomes, which is closely related to their secretion mechanism. Subsequently, the role of exosomes encapsulating different information molecules is summarized. The role of exosomes in the three phases of tumor immunoediting is introduced in detail, and the relevant literature of exosomes in the tumor immune microenvironment is summarized by using a novel framework for extracting relevant documents. Finally, it summarizes the various exosome-based immunotherapies currently proposed, as well as the challenges and future prospects of exosomes in tumor immunotherapy.

Decreased accuracy of erythrocyte sedimentation rate in diagnosing osteomyelitis in diabetic foot infection patients with severe renal impairment: A retrospective cross-sectional study.

BACKGROUND: Rapid diagnosis and treatment of diabetic foot osteomyelitis (DFO) could reduce the risk of amputation and death in patients with diabetic foot infection (DFI). Erythrocyte sedimentation rate (ESR) is considered the most useful serum inflammatory marker for the diagnosis of DFO. However, whether severe renal impairment (SRI) affects its diagnostic accuracy has not been reported previously. OBJECTIVE: To investigate the accuracy of ESR in diagnosing DFO in DFI patients with and without SRI. METHODS: This was a retrospective cross-sectional study. From the inpatient electronic medical record system, the investigators extracted demographic information, diagnostic information, and laboratory test results of patients with DFI who had been hospitalized in Longhua Hospital from January 1, 2016 to September 30, 2021. Logistic regression was performed to analyze the interaction between ESR and SRI with adjustment for potential confounders. The area under the curve (AUC), cutoff point, sensitivity, specificity, prevalence, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) were analyzed by receiver operating characteristic (ROC) curve analysis and VassarStats. RESULTS: A total of 364 DFI patients were included in the analysis. The logistic regression analysis results showed that elevated ESR increased the probability of diagnosing DFO (adjusted odds ratio [OR], 2.40; 95% confidence interval [CI], 1.75-3.28; adjusted P < 0.001); SRI was not associated with the diagnosis of DFO (adjusted OR, 3.20; 95% CI, 0.40-25.32; adjusted P = 0.271), but it had an obstructive effect on the diagnosis of DFO by ESR (adjusted OR, 0.48; 95% CI, 0.23-0.99; adjusted P = 0.048). ROC analysis in DFI patients without SRI revealed that the AUC of ESR to diagnose DFO was 0.76 (95% CI, 0.71-0.81), with the cutoff value of 45 mm/h (sensitivity, 67.8%; specificity, 78.0%; prevalence, 44.7%; PPV, 71.3%; NPV, 75.0%; LR+, 3.08; LR-, 0.41). In contrast, in patients with SRI, the AUC of ESR to diagnose DFO was 0.57 (95% CI, 0.40-0.75), with the cutoff value of 42 mm/h (sensitivity, 95.0%; specificity, 29.2%; prevalence, 45.5%; PPV, 52.8%; NPV, 87.5%; LR+, 1.34; LR-, 0.17). CONCLUSIONS: The accuracy of ESR in diagnosing DFO in DFI patients with SRI is reduced, and it may not have clinical diagnostic value in these patients.

The role of eIF5A in epidermal growth factor-induced proliferation of corneal epithelial cell association with PI3-k/Akt activation.

PURPOSE: After excimer laser surgery, epidermal growth factor (EGF) plays an important role in injured corneal epithelial cell on myofibroblastic cell formation in corneal stroma. The purpose of the study is to investigate the precise mechanism of EGF on corneal wound healing, particularly on epithelial proliferation and migration. METHODS: In this study we applied small interference RNA (siRNA) to knock down the expression of eukaryotic translation initiation factor 5A (eIF5A) in corneal epithelial cells. The relative mRNA and protein expression of matrix metallopeptidase 9 (MMP9) and proliferating cell nuclear antigen (PCNA) was determined via real-time PCR and western blot analysis. The proliferative potential of EGF was evaluated via a proliferation assay using the measurement of (3)H-thymidine incorporation ((3)H-TdR). HCEpiC apoptosis was subjected to flow cytometric analysis. RESULTS: The results showed eIF5A expression was enhanced and there was a statistically significant increase in EGF treatment compared to the control group. Real-time PCR, western blot analysis, and the proliferation assay demonstrated significantly lower MMP9 and PCNA expression and proliferation cell counts in eIF5A siRNA-treated groups versus significantly higher levels in EGF plus eIF5A siRNA-treated groups. The data analysis showed that eIF5A, MMP9, and PCNA expression decreased as a result of the inhibitor LY294002. Apoptotic cells were increased in the EGF plus eIF5A siRNA, EGF plus LY294002, and EGF plus eIF5A siRNA plus LY294002 groups as compared with the EGF siRNA group. CONCLUSIONS: These results indicate that EGF-induced upregulation of eIF5A stimulates corneal epithelial cell proliferation in vitro. EGF stimulation of corneal epithelial proliferation was through the phosphatidylinositol 3-kinase (PI3-k)/protein kinase B (Akt) signaling pathway.