The Role of IL-6, IL-10, and TNF-α in Ocular GVHD Following Allogeneic Transplantation.

PURPOSE: To figure out the roles of tear inflammatory cytokines in Ocular graft-versus-host disease (oGVHD) symptoms by analyzing tear cytokine levels and related factors. METHODS: This prospective study involved 27 post-HSCT patients and 19 controls with dry eye disease. Analyses included tear cytokine (IL-6, IL-10, and TNF-α), ocular surface evaluation, and conjunctival impression cell examination. Tear cytokine levels were evaluated in three grades of corneal epithelial lesions. The study also analyzed the correlation between tear cytokine levels and ocular surface parameters. Tear cytokine levels were then used in a Receiver Operating Characteristic (ROC) curve and linear regression model to predict oGVHD related factors. RESULTS: IL-6 has good diagnostic efficacy in oGVHD related dry eye. Elevated levels of tear IL-6 and TNF-α were observed in the group with severe corneal epithelial lesions. IL-6 levels were positively correlated with corneal fluorescein staining (CFS), eyelid margin hyperemia, conjunctival lesions, and meibum secretion. IL-6 showed excellent predictive ability with Area Under the Curve (AUC) values all greater than 0.70 (p < 0.05). IL-10 and TNF-α were negatively correlated with the meibomian gland proportion and conjunctival goblet cell (GC) density, while TNF-α was positively correlated with CFS and eyelid margin hyperemia. CONCLUSION: Dry eye symptoms related to ocular GVHD, can be partly diagnosed and assessed using various tear cytokine level detection methods.

Study on Related Factors of the Treatment Zone After Wearing Paragon CRT and Euclid Orthokeratology Lenses.

OBJECTIVE: To explore the influence factors of the treatment zone diameter (TZD) and its relationship with axial length growth (ALG) after wearing Paragon CRT and Euclid orthokeratology lenses. METHODS: The right eye data of myopic patients wearing Paragon CRT and Euclid orthokeratology in the ophthalmology department of The First Affiliated Hospital of Soochow University were retrospectively reviewed from April 2019 to October 2022. The TZD and ALG were compared between the Paragon CRT and Euclid groups. The correlation factors of TZD after wearing lens for 1 month and the relationship between the overlapping treatment zone-to-pupil area ratio and the ALG after wearing lens for 1 year were analyzed between the two groups. RESULTS: There were 160 patients (160 eyes) in the Paragon CRT group and 155 patients (155 eyes) in the Euclid group. After wearing lens for 1 month, the TZD in the Paragon CRT group (3.72±0.37 mm) was larger than that in the Euclid group (3.26±0.37 mm) ( P <0.001). The stepwise multivariate linear regression analysis showed that the eccentricity at the flattest meridians (Em) and the central corneal thickness were correlated with the TZD in both groups ( P <0.05). After wearing lens for 1 year, the ALG in the Paragon CRT group (0.32±0.20 mm) was larger than that in the Euclid group (0.25±0.20 mm) ( P =0.001). The stepwise multivariate linear regression analysis showed that the initial wearing age and the overlapping treatment zone area-to-pupil area ratio were correlated with the ALG in both groups ( P <0.05). CONCLUSION: For both the Paragon CRT and Euclid orthokeratology, the wearers with thicker central corneal thickness and smaller Em usually had a smaller TZD. In both groups, the overlapping treatment zone area-to-pupil area ratio was correlated with the ALG.

p53-regulated lncRNAs in cancers: from proliferation and metastasis to therapy.

Long non-coding RNAs (lncRNAs) have been identified as master gene regulators through various mechanisms such as transcription, translation, protein modification and RNA-protein complexes. LncRNA dysregulation is frequently associated with a variety of biological functions and human diseases including cancer. The p53 network is a key tumor-suppressive mechanism that transcriptionally activates target genes to suppress cellular proliferation in human malignancies. Recent research indicates that lncRNAs play an important role in the p53 signaling pathway. In this review, we summarize the current knowledge of lncRNAs in p53-relevant functions and provide an overview of how these altered lncRNAs contribute to tumor initiation and progression. We also discuss the association between lncRNA and up- or downstream genes of p53. These findings imply that lncRNAs can help identify cellular vulnerabilities that may prove to be promising potential biomarkers and therapeutic targets for cancer treatment.

LKG-Net: lightweight keratoconus grading network based on corneal topography.

Keratoconus (KC) is a noninflammatory ectatic disease characterized by progressive thinning and an apical cone-shaped protrusion of the cornea. In recent years, more and more researchers have been committed to automatic and semi-automatic KC detection based on corneal topography. However, there are few studies about the severity grading of KC, which is particularly important for the treatment of KC. In this work, we propose a lightweight KC grading network (LKG-Net) for 4-level KC grading (Normal, Mild, Moderate, and Severe). First of all, we use depth-wise separable convolution to design a novel feature extraction block based on the self-attention mechanism, which can not only extract rich features but also reduce feature redundancy and greatly reduce the number of parameters. Then, to improve the model performance, a multi-level feature fusion module is proposed to fuse features from the upper and lower levels to obtain more abundant and effective features. The proposed LKG-Net was evaluated on the corneal topography of 488 eyes from 281 people with 4-fold cross-validation. Compared with other state-of-the-art classification methods, the proposed method achieves 89.55% for weighted recall (W_R), 89.98% for weighted precision (W_P), 89.50% for weighted F1 score (W_F1) and 94.38% for Kappa, respectively. In addition, the LKG-Net is also evaluated on KC screening, and the experimental results show the effectiveness.

Correlative factors of ocular surface lesions after allogeneic hematopoietic stem cell transplantation: A retrospective study.

Background: Ocular graft-versus-host disease (oGVHD) is one of the complications after allogeneic hematopoietic stem cell transplantation (HSCT), which impairs the quality of life and may indicate poor prognosis. In this retrospective study, the aim was to investigate the characteristics of ocular surface after HSCT, and analyze the risk factors related to the severity of ocular surface lesions. Methods: 248 post-HSCT patients were enrolled in this retrospective study. Subjects were divided into no lesion group, mild lesion group and severe lesion group, according to the severity of ocular surface lesions. The correlations between grades of ocular surface lesions and gender, age, primary disease, donor source, human leukocyte antigen (HLA) type, kinship, donor-recipient relationship, blood type, source of stem cell and systemic GVHD were analyzed. Results: The median scores of corneal epitheliopathy, lid margin lesions and meibomian gland loss were 3, 6 and 2 points, respectively. The grade of corneal epitheliopathy was related to donor source (P<0.001), kinship (P=0.033), HLA-matching (P<0.001), and systemic GVHD (P=0.007), especially oral GVHD (P<0.001) and liver GVHD (P=0.002). The grade of lid margin lesions was related to donor source (P=0.019), HLA-matching (P=0.006), and systemic GVHD (P=0.013), especially skin GVHD (P=0.019) and oral GVHD (P=0.019). The grade of meibomian gland loss was related to age (P=0.035) and gastrointestinal GVHD (P=0.007). The grade of corneal epitheliopathy after HSCT was related to the lid margin lesion score (P<0.001). Conclusions: The occurrence and development of ocular GVHD are mostly accompanied by the history of systemic GVHD. While in few cases, ocular surface lesions related to GVHD can be observed prior to the rejection of other tissues and organs. Severe corneal epitheliopathy occurs in patients with severe lid margin lesions in ocular GVHD. The lesions of corneal epithelium and lid margin are milder in HLA partially matching transplantation.

Corneal perforation associated with ocular graft-versus-host disease.

Corneal perforation is a rare and serious complication of ocular graft-versus-host disease (oGVHD) patients. This study was to retrospectively report seven corneal perforation patients after allogeneic hematopoietic stem cell transplantation (HSCT). Demographic, hematologic, and ophthalmological data of patients were clarified in detail. Nine eyes of seven corneal perforation patients were clarified (Cases 3 and 6 were bilateral and the others are unilateral). All the cases had other affected GVHD organs, especially skin involvement. The duration between HSCT and corneal perforation was usually long with 21 (17-145) months as median interval, whereas the duration between oGVHD diagnosis and corneal perforation was relatively shorter with 4 (2-81) months as median interval. Most patients presented to ophthalmology department with poor visual acuity, BUT and Schirmer's test. Eyelid marginal hyperemia and irregularity were observed in most corneal perforation eyes. Keratoplasty or conjunctival flap covering (CFC) surgeries was performed after corneal perforation. After a long-term follow-up for most patients (median 21 months, range: 2-86 months), only two eyes of two patients (22.22%) had a final BCVA of 20/100 or better. Patients involved in both cutaneous GVHD and blepharitis indicate the aggressive development of oGVHD. Early diagnosis, long-term follow-up, and effective multi-disciplinary treatments for oGVHD patients are essential. Corticosteroids and immunosuppressor remain essential, whereas the use of topical corticosteroids should be carefully considered in corneal ulceration patients. In addition, appropriate surgeries should be performed to control oGVHD development in time.

Fear of future workplace violence and its influencing factors among nurses in Shandong, China: a cross-sectional study.

BACKGROUND: Fear of workplace violence has become a critical issue worldwide, which can lead to burnout, low levels of job satisfaction, and turnover. However, to date, little attention has been directed toward fear of workplace violence among nurses. Accordingly, this study investigated the level of fear of future workplace violence and its influencing factors among nurses in Shandong, China. METHODS: A cross-sectional study was conducted from July 30 through September 30, 2020 in Shandong Province, China. A total of 1898 nurses were enrolled from 12 tertiary hospitals. Fear of future workplace violence was measured using the Fear of Future Violence at Work scale. Demographic information, employment characteristics, social support, and experience of workplace violence were assessed. Multiple linear regression analysis was used to explore the influencing factors of fear of future workplace violence. RESULTS: The average score of fear of future violence at work was 67.43 ± 17.20 among nurses. Multiple linear regression analysis showed that higher fear of future violence at work scores were reported among nurses who were female (B = 7.10, p < 0.001), married (B = 3.50, p = 0.028), with a monthly income ≥5000 Chinese yuan (CNY) (B = 3.14, p = 0.007), working in the department of internal medicine (B = 2.90, p = 0.032), surgery (B = 5.03, p < 0.001), pediatrics (B = 5.38, p = 0.003), or emergency department (B = 4.50, p = 0.010), working as a contract employee (B = 2.41, p = 0.042), or who had experienced workplace violence (B = 7.02, p < 0.001). Lower fear of future violence at work scores were found among nurses who took vacations (1-14 days: B = - 2.52, p = 0.047; ≥15 days: B = - 3.69, p = 0.007) and had a high-level of social support (B = - 2.03, p = 0.020). CONCLUSIONS: There was a high level of fear of future workplace violence among nurses in Shandong, China. This should be considered an important issue by hospital administrators and government officials. Effective interventions need to be enacted to address the influencing factors of fear of future workplace violence.

The association between fear of future workplace violence and burnout among nurses in China: A cross-sectional study.

BACKGROUND: Fear of future workplace violence has adverse effects on nurses' health outcomes. However, the association between fear of future workplace violence and burnout among nurses in China remains unknown. METHODS: Enrolled in the study were 1897 nurses from 12 tertiary hospitals of Shandong Province, China. Fear of future workplace violence was measured using the Fear of Future Violence at Work scale. Burnout was measured using the 15-item Maslach Burnout Service Inventory. Ordinal logistic regression analysis was used to examine the association between fear of future workplace violence and burnout. RESULTS: The prevalence of high emotional exhaustion, high cynicism, and low personal accomplishment was 26.7%, 38.1%, and 35.6%, respectively, while 72.9% of participants had high levels of fear of future workplace violence. Among nurses, compared with high levels of fear of future workplace violence, low levels of fear were associated with a lower degree of emotional exhaustion, cynicism, and personal accomplishment; and medium levels of fear were associated with a lower degree of emotional exhaustion, cynicism, and a higher degree of personal accomplishment. LIMITATIONS: This was a cross-sectional study, which could not establish the causal relationship between fear of future workplace violence and burnout. CONCLUSION: There was a significant association between fear of future workplace violence and burnout among nurses. Fear of future workplace violence should be regarded as important issue for hospital administrators and healthcare policy makers when taking measures to ameliorate nurses' burnout.

Carbonic Anhydrase 4 serves as a Clinicopathological Biomarker for Outcomes and Immune Infiltration in Renal Cell Carcinoma, Lower Grade Glioma, Lung Adenocarcinoma and Uveal Melanoma.

Background: Carbonic anhydrase 4 (CA4) maintains homeostasis of carbon dioxide and bicarbonate. It is suggested to be a potential prognostic biomarker, while the correlations between CA4 and different cancers are indistinct. Methods: Differential mRNA expression of CA4 among different cancers and corresponding normal tissues was compared based on datasets on the Cancer Genome Atlas (TCGA) platforms. Then, survival analysis was performed using Tumor-immune system interactionsplatform and TCGA cohort on the basis of distinct comparison expression of CA4 in five kinds of tumors. In addition, molecular penal analysis and functional annotations of CA4-related genes was elaborated. The correlation between CA4 mRNA expression and tumor immune microenvironment were analyzed in detail. Results: Compared with adjacent normal tissues, CA4 mRNA expressions were found significantly lower in various tumors. Moreover, decreased expression of CA4 was significantly related to worse overall survival (OS) and progression-free survival (PFS) in kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), lung adenocarcinoma (LUAD) and uveal melanoma (UVM), and worse OS of prostate adenocarcinoma (PRAD) (p<0.05). Cox regression analyses indicated that CA4 was a significant prognostic biomarker in KIRC, LGG, LUAD and UVM. Moreover, CA4 showed markedly relationship with tumor immune environment and diverse immune infiltration signatures in KIRC, LGG, LUAD and UVM. Conclusions: Our study revealed that CA4 was a potential biomarker for aggressive progression and poor prognosis in KIRC, LGG, LUAD, PRAD and UVM, correlated with immune infiltration in various tumor environments. These results suggested that CA4 possibly served as a promising prognostic and immune infiltration biomarker in many cancers.

Functional Annotations of Single-Nucleotide Polymorphism (SNP)-Based and Gene-Based Genome-Wide Association Studies Show Genes Affecting Keratitis Susceptibility.

BACKGROUND Keratitis is a complex condition in humans and is the second most common cause of legal blindness worldwide. MATERIAL AND METHODS To reveal the genomic loci underlying keratitis, we performed functional annotations of SNP-based and gene-based genome-wide association studies of keratitis in the UK Biobank (UKB) cohort with 337 199 subjects of European ancestry. RESULTS The publicly available SNP-based association results showed a total of 34 SNPs, from 14 distinct loci, associated with keratitis in the UKB. Gene-based association analysis identified 2 significant genes: IQCF3 (p=2.0×10⁻6) and SOD3 (p=2.0×10⁻6). Thirty-two candidate genes were then prioritized using information from multiple sources. The overlap of IQCF3 in these 2 analyses resulted in a total of 33 hub genes. Functional annotation of hub genes was performed and transcriptional factors of IQCF3 and SOD3 were predicted. CONCLUSIONS A total of 34 SNPs from 14 distinct loci were identified as being associated with keratitis, and 32 candidate genes were then prioritized. In addition, IQCF3 and SOD3 were identified by their p values through gene-based tests on the basis of individual SNP-based tests. The functional relationship between these suspect genes and keratitis suggest that IQCF3 and SOD3 are candidate genes underlying keratitis.

Postnatal variation of limb bones in the Japanese quail, Coturnix coturnix japonica / Variación postnatal de huesos de los miembros en la codorniz japonesa, Coturnix coturnix japonica

Changes in body size over ontogeny may influence the ontogenetic development of long bones, and thus important to our understanding of variation in morphological, physiological, and life-history traits within species. In this study, we sample the entire measurements of the Japanese quail (Coturnix coturnix japonica) of individual skeletons, to investigate the ontogenetic allometry of limb bone proportions by Reduced Major Axis (RMA) regression. The ulna and humerus were both positively allometric in relation to body mass, with their proximal ends growth more rapidly than other regions. Hindlimb bones exhibited more than one allometric pattern. The tarsometatarsus was negative; the femur presented positive allometry, with the width and depth of the proximal end scaled more strongly; measurements of the tibiotarsus were dominated by more rapid growth, especially the width of the proximal end. The growth patterns are suggested to be correlated with the ontogeny of behavior, and reflect the muscular requirements for different mode of locomotion.

Los cambios en el tamaño corporal sobre la ontogenia pueden influir en el desarrollo ontogenético de los huesos largos, y por lo tanto es importante conocer la variación en sus rasgos morfológicos, fisiológicos y la historia de vida dentro de las especies. En este estudio, se muestran las mediciones completas de esqueletos individuales de codorniz japonesa (Coturnix coturnix japonica), para investigar la alometría ontogenética de las proporciones de los huesos de los miembros mediante la regresión del Eje Mayor Reducido (RMA). La ulna y el húmero fueron ambos positivos alométricamente en relación a la masa corporal, con un crecimiento más ligero de sus extremos proximales que de otras regiones. Los huesos de los miembros posteriores mostraron más de un patrón alométrico. El tarsometatarsus fue negativo; el fémur presentó alometría positiva, con un ancho y profundidad del extremo proximal importantes. Las mediciones del tibiotarso presentaron un crecimiento más rápido, sobre todo la anchura del extremo proximal. Los patrones de crecimiento sugieren estar correlacionados con la ontogenia de la conducta, y reflejan los requisitos musculares para un modo de locomoción diferente.