The photothermal effect of intense pulsed light and LipiFlow in eyelid related ocular surface diseases: Meibomian gland dysfunction, Demodex and blepharitis.

The treatment and management of ocular surface diseases have shifted towards a co-treatment approach focusing on overall ocular surface homeostasis. When treating issues related to the eye, it is essential to not only focus on the damaged or disabled areas but also consider the larger picture. Meibomian gland dysfunction (MGD), Demodex infection, and blepharitis all interact at the eyelid site and can cause damage to the ocular surface to varying degrees. Palpebral lesions disrupt the balance of ocular surface homeostasis, leading to dry eye and keratitis. Traditional treatments, such as manual physical hot compress massage, have limited effectiveness due to the structure of the eyelid. However, intense pulsed light (IPL) technology uses penetrating light energy to generate heat energy, which can eliminate inflammation of capillaries or kill Demodex. Additionally, the LipiFlow thermal effect and physical compression provide a more vital and longer-lasting therapeutic effect on MGD by excluding other primary causes of ocular surface inflammation. Therefore, personalized treatment techniques based on photothermal effects may be effective. In the future, IPL and LipiFlow may potentially dismiss immune-inflammation factors causing ocular surface disease or block the delivery of systemic immune-related diseases.

Inflammation due to ocular surface homeostasis imbalance caused by pterygia: tear lymphotoxin-alpha study and a literature review.

OBJECTIVE: To estimate the pterygium ocular surface state, and compare with healthy eyes and dry eyes. To investigate the inflammation due to pterygia growth by tear Lymphotoxin-alpha (LT α) test. DESIGN: Prospective, single-center study. PARTICIPANTS: 400 patients, divided into 100 pterygium group, 100 mild dry eye group, 100 moderate dry eye group, and 100 age-and sex-matched normal controls. METHODS: The non-invasive break-up time (NIBUT), tear meniscus height (TMH) test, corneal fluorescein staining (CFS), meibomian gland loss score (MGs), and lipid layer thickness (LLT) were evaluated in all patients. Pterygium status and ocular status in the pterygium group were collected. The tear LT α test was conducted in the pterygium patients group. RESULT: Pterygium can affect the ocular surface, leading to decreased tear film stability. The TMH, NIBUT, CFS, MGs, and lipid layer thickness can provide insights into this phenomenon. The presence of pterygium can change the structure and condition of the ocular surface. Tear LT α testing shows an abnormal decrease in LT α levels in pterygium patients. This indicates an immune-inflammation microenvironment that causes tissue repair deficiency. CONCLUSION: The dry eye triggered by the growth of pterygium may originate from the tear film instability due to pterygia. As an inflammatory index, LT α in the development of pterygium and the aggravation of dry eye patients can indicate that the ocular surface is in different inflammatory states. Future tear testing in LT α may be a potential indicator to assess the inflammatory status of the dry eye.

Clinical features and comprehensive treatment of persistent corneal epithelial dysfunction after cataract surgery.

OBJECTIVE: Evaluation of clinical efficacy and safety of tobramycin/dexamethasone eye ointment in treating persistent corneal epithelial dysfunction (PED) after cataract surgery. METHODS: 26 cases diagnosed as PED after cataract surgery accept the tobramycin/dexamethasone ophthalmic ointment and intense pulse light treatment in the Xiamen University of Xiamen eye center between September 2016 and April 2022 were retrospectively analyzed, mainly including clinical manifestations, characteristics of morphological changes imaged by in vivo confocal microscopy, meibomian glands infrared photography, lipid layer thickness (LLT), management and therapeutic effects. RESULTS: There were 26 eyes, include 8(35%) males and 15(65%) females with an average age of 69.6 ± 5.2 years(50 to 78 years). The mean hospitalization time was (18.4 ± 7.5) days after cataract surgery. Twenty patients had meibomian gland dysfunction. Infrared photography revealed varying loss in the meibomian glands, with a mean score of 3.8 ± 1.2 for gland loss. The mean LLT was 61.6 ± 8.4 nm. After treatment, 20 patients were cured, and 3 received amniotic membrane transplantation. After treatment, the uncorrected visual acuity (UCVA) and best-corrected vision activity (BCVA) improved (P < 0.001), and there was no significant difference in intraocular pressure (IOP) before and after treatment (P > 0.05). CONCLUSIONS: The early manifestation of PED after surgery is punctate staining of the corneal epithelium. Tobramycin and dexamethasone eye ointment bandages have a good repair effect. The meibomian gland massage combined with intense pulse light treatment can effectively shorten the course of the disease.

Evaluation of lymphotoxin-alpha in pterygium and diagnostic value in active and inactive pterygium states.

To explore the correlation between tear LT-a, pterygium status, and dry eye indicators. We established a diagnostic model to evaluate active pterygium. A retrospective study was conducted between June 2021 and June 2023 on 172 patients, comprising 108 men and 64 women. The study analyzed LT-a and various ocular parameters in all participants. The data was collected using Excel software and analyzed using SPSS 25.0 statistical software and Medcalc. We made a nomogram diagnostic model to different diagnosed the state of pterygium. This study found that pterygium has progressive eye surface damage during the active state. There was no significant difference in dry eye indicators between the two groups. However, the concentration of LT-a in the active group was significantly lower than that in the inactive group (P < 0.001). We observed that increased pterygium grade corresponded to a worse ocular surface condition. In addition, LT-a was significantly positively correlated with disease duration, but negatively correlated with age, pterygium size, active pterygium state, and LLT value. The optimal intercept value for evaluating active pterygium in Lt-a was ≤ 0.49 dg/ml. We screened three variables for evaluating active pterygium through Single and Multiple regression analysis: LT-a grading, pterygium size, and congestion score. Finally, we made a reliable diagnostic nomogram model. Pterygium development triggers immune inflammation. Our model based on LT-a identifies active pterygium for personalized treatment options and new research directions.

Clinical and Morphological in Vivo Confocal Microscopy Findings following a Modified Biphasic Higher Fluence Transepithelial Corneal Crosslinking.

Purpose: To compare the refractive efficacy and morphological changes in the cornea following a novel biphasic higher fluence transepithelial corneal crosslinking (BI-TE-CXL) and transepithelial corneal crosslinking (TE-CXL) in adults keratoconus.Methods: Patients with progressive keratoconus who required corneal crosslinking were assigned to the BI-TE-CXL group (32 eyes, phase 1: 7.2 J/cm2 for 5 min and 20 s of pulsed-light exposure, KXL, Glaukos-Avedro; phase 2: 3.6 J/cm2 for 6 min and 40 s of continuous light exposure at the front curvature apex with a 6 mm diameter light spot, UVX-2000, IROC) or the TE-CXL group (32 eyes, uniform 7.2 J/cm2 for 5 min and 20 s of pulsed-light exposure, KXL, Glaukos-Avedro). Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), corneal fluorescein staining (CFS), corneal topography, anterior segment optical coherence tomography (AS-OCT), and in vivo corneal confocal microscopy (IVCM) were performed 3, 6, 12 and 24 months after surgery.Results: The CFS scores in the BI-TE-CXL group were significantly higher than those in the TE-CXL group on the first two days after surgery (p < 0.001). The Kmax (at 12 and 24 months) and CDVA (logMAR) were significantly lower in the BI-TE-CXL group than those in the TE-CXL group (p < 0.05). The corneal demarcation line under AS-OCT was visible in 81.3% of patients in the BI-TE-CXL group and 15.6% in the TE-CXL group. The depth of the demarcation line under IVCM was significantly deeper in the BI-TE-CXL group (248.3 ± 25.0 µm) than that of the TE-CXL group (136.5 ± 15.6 µm) in the central cornea (p < 0.001). The cross-linked collagen structures in the central cornea were still present after 12 months in the BI-TE-CXL group. No significant difference in sub-basal nerve density between the two groups (p > 0.05).Conclusions: Following BI-TE-CXL, CDVA was significantly improved, accompanied by deeper demarcation line depth and persistent crosslinked structures in the central corneal stroma.

Relation Between Corneal Dendritic Cell Density and Tear Film Stability in Patients with Epidemic Keratoconjunctivitis Associated Dry Eye.

PURPOSE: To clarify the ocular surface features of patients with recent history of epidemic keratoconjunctivitis (EKC) and the relation between corneal dendritic cells (DCs) and ocular discomfort. METHODS: Normal controls (NC) and dry eye (DE) patients without EKC were recruited. Patients with recent EKC history (onset >4 weeks, but <20 weeks) were recruited as EKC + DE group (with dry eye) or EKC-DE group (without dry eye). Ocular surface disease index (OSDI) questionnaire, tear film parameters including lipid layer thickness, first tear break-up time (fBUT), average tear break-up time (aBUT), tear meniscus height and Schirmer I test, meibomian gland parameters, and in vivo corneal confocal microscopy were evaluated. RESULTS: 50 subjects in the NC group, 83 patients in the DE group, 76 patients in the EKC + DE group, and 38 patients in the EKC-DE group were included. Compared with the NC, DE, and EKC-DE groups, the EKC + DE group represented higher OSDI, lid margin, and meibum score (p < 0.05). In the EKC + DE group, the tear volume (10.5 ± 3.7 mm) was significantly higher than in the DE group (8.1 ± 2.8 mm, p < 0.001). The DC density in the EKC + DE group (29.98 ± 15.38 cells/image) was significantly higher than in NC, DE, and EKC-DE groups (4.68 ± 4.05 cells/image) (p < 0.001). The DC density was positively correlated with OSDI, lid margin, and meibum score (all p < 0.01) while inversely correlated with fBUT, aBUT (all p < 0.001) in the EKC + DE group. CONCLUSIONS: Corneal DC density significantly correlates to ocular discomfort and tear film instability in patients with recent EKC history who suffer from DE without aqueous tear deficiency.

The clinicopathological analysis of ocular and orbit tumors in southeast of China.

Purpose: The purpose of this study is to describe the clinicopathologic characteristics of ocular surface and orbit tumors in the Southeast of China and explore the method to differentiate the benign and malignant masses. Materials and methods: 3468 patients undergoing mass resection from January 2015 to December 2020 were selected as observation subjects and were classified into benign and malignant masses according to postoperative pathology. The clinicopathologic characteristics were collected, including gender, age, pathological tissue signs, and pathological signs. Multivariate Logistic regression analysis of independent risk factors of malignant mass was applied to establish a diagnostic model and the efficacy was evaluated by the subject working characteristics (ROC) curve. Results: Benign tumors accounted for 91.5% of all cases, and malignant tumors accounted for 8.5%. The most common ocular benign tumors were nevi (24.2%), granuloma (17.1%), and cysts (16.4%). The most common ocular malignant tumors were malignant lymphoma (32.1%) and Basal cell carcinoma (20.2%). As for the histologic origin, melanocytic origin was on the list with 819 (23.6%), mesenchymal 661 (19.1%), epithelial 568 (16.3%), cystic 521 (15.0%), skin adnexal 110 (3.1%), lymphoid 94 (2.8%), and Neural 25(0.8%). Based on the gender, age, tumor location, and the pathological tissue image feature (including differentiation, structural atypia, covering epithelial, keratosis, nest structure/distribution, nuclear atypia, cytoplasmic change and nuclear division), the diagnostic model had predictive value to differentiate the benign and malignant masses. Conclusion: Most ocular surface and orbit tumors are benign. Tumor diagnosis is relative to the patient's age, gender, tumor location, and pathologic characteristics. We generated a satisfactory diagnostic model to differential diagnosis of benign and malignant masses.

Histopathology-based diagnosis of Mooren's ulcer concealed beneath the pterygium on eye.

Mooren's ulcer (MU) is a chronic and painful ulcerative keratitis that is difficult to diagnose, especially when concealed beneath the pterygium, which is a common, benign, wedge-shaped, fleshy tissue growth of the conjunctiva extending onto the cornea. The coexistence of MU and pterygium is extremely rare. A 41-year-old man presented with a 2-month history of unprovoked redness, pain, and blurred vision in the right eye. Corneal epithelial defects around the pterygium head were noted upon slit-lamp examination and fluorescein staining. The patient was initially misdiagnosed with a corneal epithelial defect and pterygium. The initial treatments with anti-inflammatory and corneal epithelial growth promotion tear agents failed. Anterior segment optical coherence tomography (AS-OCT) showed corneal stromal lysis thinning, and in vivo confocal microscopy (IVCM) revealed marked inflammatory cell infiltration and stromal degeneration. We suspected the pathology was an immune-related or tumor-related corneal ulcer. The MU concealed beneath the pterygium was diagnosed by histopathological examination of a biopsy specimen that presented typical localized loss of the corneal epithelium and Bowman's layer, stromal degeneration, and inflammatory cell infiltration. Finally, we performed lamellar keratoplasty (LKP) combined with pterygium excision surgery. The patient recovered with no complications or recurrence during the 1-year follow-up period. Few cases of MU concealed beneath the pterygium have been reported. It is beneficial to rule out the pathological changes concealed beneath the pterygium, combined with multiple means of examination such as slit-lamp examination, AS-OCT, and IVCM. A histopathological examination should be performed to establish a diagnosis.

Meibomian Glands and Tear Film Findings in Type 2 Diabetic Patients: A Cross-Sectional Study.

Background: The characteristics of the meibomian gland and tear film in patients with type 2 diabetes (T2D) with different glycemic control levels and diabetic durations remain largely unexplored. This study aimed to identify the association of dry eye and meibomian gland dysfunction (MGD) in T2D. Materials and Methods: Ninety-nine patients with type 2 diabetes mellitus (DM group), 33 dry eye patients without diabetes mellitus (DE group), and 40 normal subjects (NC group) were recruited for this study. Participants were evaluated with an Ocular Surface Disease Index (OSDI) questionnaire, tear film breakup time (BUT), the Schirmer I test (SIT), corneal fluorescein staining (FL), lipid layer thickness (LLT), and MGD parameters. Glycosylated hemoglobin (HbA1c ) and duration of diabetes were recorded. Results: The SIT value in the DM group was higher than that of the DE group (p < 0.05). The BUT and LLT were lower, and MGD parameters were higher in the DM group than those of the DE and NC groups (p < 0.05). In the DM group, 47 patients were diagnosed with dry eye (DM + DE group), whereas 40 patients without dry eye were categorized as the DM - DE group. The SIT, BUT, and LLT values in the DM - DE group were higher (p < 0.01), and MGD parameters were lower (p < 0.01) in the DM - DE group than those of the DM + DE group. The MGD parameters were higher in the DM - DE group than those in the NC group (p < 0.05). The HbA1c levels were correlated with OSDI, BUT, LLT, FL, and MGD parameters (p < 0.001) in the DM group. However, in patients with low HbA1c , normal SIT value, and low OSDI, the MGD parameters were higher than those in the NC group (p < 0.05). The duration of diabetes positively correlated with MGD parameters (p < 0.001). Conclusion: Asymptomatic MGD may be an early sign of dry eye and ocular discomfort in T2D. The MGD parameters were associated with the HbA1c level and diabetic duration.

Effects of Sodium Hyaluronate Eye Drops With or Without Preservatives on Ocular Surface Bacterial Microbiota.

PURPOSE: This study aimed to determine the composition and diversity of bacterial communities on the ocular surface before and after the intervention with sodium hyaluronate eye drops (with or without preservatives) using 16S rRNA gene amplicon sequencing. METHODS: Sixteen healthy adults were randomly divided into two groups and treated with sodium hyaluronate eye drops with or without preservatives for 2 weeks. The individuals used the same artificial tears in both eyes. The microbial samples from the conjunctival sac of each participant were collected at baseline and 2 weeks after intervention. The diversity and taxonomic differences among different groups before and after intervention were compared by sequencing the V3-V4 region of the 16S rRNA gene. RESULTS: The similarity in the binocular microbial community was high in 1 of the 16 volunteers (Bray-Curtis dissimilarity score < 0.3). At the genus level, 11 bacteria were detected in all samples with an average relative abundance of more than 1%. The bacterial community changed significantly after the use of sodium hyaluronate eye drops (with or without preservatives), whether within individuals or between individuals in different groups (P < 0.05, PERMANOVA). Different dosage forms of sodium hyaluronate eye drops significantly decreased the relative abundance of Flavobacterium caeni and Deinococcus antarcticus, respectively (P < 0.05). CONCLUSIONS: Healthy people had a rich diversity of the bacterial microbiota on the ocular surface, but the bacterial communities between the eyes were not completely similar. Irrespective of containing benzalkonium chloride (BAC), sodium hyaluronate eye drops can change the bacterial community on the ocular surface.

The Expression of Three Negative Co-Stimulatory B7 Family Molecules in Small Cell Lung Cancer and Their Effect on Prognosis.

BACKGROUND: In recent years, immune checkpoint inhibitors have shown significant effects in a variety of solid tumors. However, due to the low incidence of small cell lung cancer (SCLC) and its unclear mechanism, immune checkpoints in SCLC have not been fully studied. METHODS: We evaluated the expression of PD-L1, B7-H3, and B7-H4 in 115 SCLC tissue specimens using immunohistochemistry. The clinical data of patients with SCLC were retrospectively reviewed to investigate three negative co-stimulatory B7 family molecules' ability to affect the prognosis of SCLC. RESULTS: Among the SCLC patients with complete follow-up data (n = 107), sixty-nine (64.49%) expressed moderate to high B7-H3 levels, which correlated positively with tumor sizes (P < 0.001). Eighty (74.77%) patients expressed moderate to high B7-H4 levels, which correlated positively with metastases (P = 0.049). The positive expression of B7-H3 and B7-H4 correlated significantly with shortened overall survival (OS) (B7-H3, P = 0.006; B7-H4, P = 0.019). PD-L1 was positively expressed only in 13.08% of cancer tissues, and there was no significant correlation with prognosis. The Cox proportional hazards regression showed that B7-H3 was an independent prognostic indicator of OS (P = 0.028; HR = 2.125 [95% CI = 0.985-4.462]). CONCLUSIONS: Our results suggest that B7-H3 has a negative predictive effect on SCLC. This outcome provides a theoretical basis for the subsequent research on immune checkpoint inhibitors targeting B7-H3.

Research on the circadian clock gene HNF4a in different malignant tumors.

Background: The circadian rhythm is produced by multiple feedback loops formed by the core clock genes after transcription and translation, thus regulating various metabolic and physiological functions of the human body. We have shown previously that the abnormal expression of 14 clock genes is related closely to the occurrence and development of different malignant tumors, and these genes may play an anti-cancer or pro-cancer role in different tumors. HNF4a has many typical properties of clock proteins involved in the clock gene negative feedback loop regulation process. We need to explore the function of HNF4a as a circadian clock gene in malignant tumors further. Methods: We used The Cancer Genome Atlas (TCGA) database to download the clinicopathological information of twenty malignant tumors and the corresponding RNA-seq data. The HNF4a RNA-seq data standardized by R language and clinical information were integrated to reveal the relationship between HNF4a and prognosis of patients. Results: Analysis of TCGA data showed that the prognosis of HNF4a was significantly different in BLCA, KIRC, LUSC, and READ. High HNF4a expression is correlated with good prognosis in BLCA, KIRC, and READ but poor prognosis in LUSC. However, HNF4a was associated with the stages, T stages, and lymph node status only in BLCA. Conclusions: HNF4a plays different roles in different malignancies, and the abnormal expression of HNF4a has a great correlation with the biological characteristics of BLCA. The low expression of HNF4a could be a reference index for the metastasis, recurrence, and prognosis of BLCA.

Safety and efficacy of repeated crosslinking assisted by transepithelial double-cycle iontophoresis in keratoconus progression after primary corneal crosslinking.

OBJECTIVES: To evaluate the safety and efficacy of repeated corneal collagen crosslinking assisted by transepithelial double-cycle iontophoresis (DI-CXL) in the management of keratoconus progression after primary CXL. METHODS: A retrospective analysis was conducted in the patients who underwent repeated CXL between 2016 and 2018. These patients were treated with DI-CXL if keratoconus progression was confirmed after primary CXL. Scoring of ocular pain and corneal epithelial damage, visual acuity, corneal tomography, in vivo corneal confocal microscopy (IVCM) was performed before and at 3, 6, 12, and 24 months after DI-CXL. RESULTS: Overall, 21 eyes of 12 patients (mean age 17.3 ± 1.9 years) were included in this study. Before DI-CXL, an average increase of 4.26 D in Kmax was detected in these patients with a mean follow-up interval of (23.0 ± 13.7) months. After DI-CXL, corneal epithelial damage rapidly recovered within days. Visual acuity remained unchanged with follow-up of 24 months. When compared to baseline, significant decreases were observed in Kmax (at 3 months) and K2 (at 3 and 6 months) after DI-CXL. Corneal thickness of thinnest point significantly decreased at 3 months postoperatively. When compared to baseline, no significant differences were found in any of the refractive or tomographic parameters at 12 and 24 months. IVCM revealed trabecular patterned hyperdense tissues after DI-CXL in the anterior stroma at the depth of 200 µm or more. No corneal infiltration or persistent epithelial defect was recorded after DI-CXL. CONCLUSION: DI-CXL is safe and effective as a good alternative in stabilizing keratoconus progression after primary CXL.

Transepithelial corneal cross-linking assisted by two continuous cycles of iontophoresis for progressive keratoconus in adults: retrospective 5-year analysis.

PURPOSE: The aim of this study is to compare the long-term effects of transepithelial corneal crosslinking with two continuous cycles of iontophoresis (EI-CXL) and conventional corneal crosslinking (C-CXL) in adults with progressive keratoconus. METHODS: A retrospective analysis was conducted in adults who underwent C-CXL or EI-CXL between 2013 and 2015. Visual acuity, corneal tomography, anterior segment optical coherence tomography, in vivo corneal confocal microscopy (IVCM), and endothelial cell count (ECC) were performed preoperatively and 5 years postoperatively. RESULTS: Sixty-eight patients with a mean age of (24.3 ± 3.8) years were included, 34 for each group. After CXL, UCVA or BCVA remained stable, while the spherical diopter, cylinder diopter, spherical equivalent, and Kmax significantly decreased at 1, 2, and 3 years in both groups than baseline (P < 0.05). No significant differences were found in any refractive or tomographic parameters as well as the minimal corneal thickness between groups during follow-up. At 5 years, Kmax was slightly higher in EI-CXL group (58.16 ± 6.28) than that of C-CXL group (57.46 ± 4.98). At 3 and 5 years, the minimal corneal thickness in C-CXL group was still significantly lower than baseline (P < 0.05). IVCM demonstrated the demarcation zone at a mean depth of (302.0 ± 41.7) µm after C-CXL, and at (251.2 ± 28.1) µm after EI-CXL (P < 0.001). Keratocyte repopulation was detectable at all follow-up timepoint in both groups. Postoperative complications including progression were recorded in 6 patients (11.7%) after C-CXL and 3 patients (8.8%) after EI-CXL. ECC remained stable in both groups. CONCLUSION: EI-CXL showed approximate efficacy with C-CXL in stabilizing progressive keratoconus in adults. EI-CXL has the potential to be a preferable transepithelial protocol.

Prognosis of primary hepatic lymphoma: A US population-based analysis.

OBJECTIVE: Primary hepatic lymphoma (PHL) is a rare malignancy with lesions confined to the liver. It is characterized by a large number of monomorphic, medium-sized lymphocytic infiltrates in the hepatic sinusoid. Due to the rarity of this malignancy, our current understanding of PHL is limited. METHODS: We collected incidence, mortality, and clinical data of PHL patients diagnosed between 1975 and 2016 using the Surveillance, Epidemiology, and End Results (SEER) database. The annual percentage changes (APCs) and prognoses were analyzed using the Joinpoint and R package. RESULTS: Among the 1,372 patients, white males were prevalent, and the most common histological subtype was diffuse large B-cell lymphoma (DLBCL). The incidence and mortality rate of PHL was 0.075/100,000 person-years and 0.055/100,000 person-years, respectively. The annual incidence rate of PHL increased significantly, with an APC of 2.74% (P < 0.001). The 3- and 5-year overall survival (OS) rates of patients with PHL were 43.553% and 39.242%, respectively. The 3- and 5-year relative survival (RS) rates were 46.925% and 45.300%, respectively. Multivariate Cox regression analysis revealed that older age, black, DLBCL, and advanced-stage disease were independent predictors of unfavorable OS and RS. The C-index and receiver operating characteristic (ROC) analysis confirmed the prognostic value of the nomograms established in this study. CONCLUSION: The nomogram established in this study is a robust tool to predict the prognosis of PHL patients.

PPAR-α Agonist Fenofibrate Suppressed the Formation of Ocular Surface Squamous Metaplasia Induced by Topical Benzalkonium Chloride.

Purpose: To investigate the effects and mechanisms of the peroxisome proliferator-activated receptor alpha (PPAR-α) agonist fenofibrate on the formation of ocular surface squamous metaplasia induced by topical benzalkonium chloride (BAC) in a mouse model. Methods: Ocular surface squamous metaplasia was induced in 16 days by topical BAC application in mice. During the period of induction, mice were divided into four groups: no additional treatment (BAC+UT), topical vehicle (BAC+Vehicle), topical fenofibrate (BAC+Feno), or topical fenofibrate plus intraperitoneal injection of MK886 (BAC+Feno+MK886). The parameters of tear film were evaluated on day 16, and eye specimens were collected. Histologic investigation; PAS assays; immunostaining for cytokeratin 10 (K10), Ki67, and F4/80; and PCR assays for TNF-α and IL-6 were performed. Cell Counting Kit 8 (CCK-8) assays were performed to evaluate the inhibitory effects of fenofibrate on RAW264.7 cells. Results: Fenofibrate suppressed the formation of BAC-induced instable tear film. In the BAC+Feno group, the expression of K10 and Ki67 was lower than in the other three groups. The number of goblet cells was reduced in eyes of the BAC+UT and BAC+Vehicle groups but was maintained in eyes of the BAC+Feno group. The number of F4/80-positive cells and the levels of TNF-α and IL-6 mRNA were significantly reduced in the cornea of the BAC+Feno group. These effects of fenofibrate could be attenuated by MK886. The cell viability of RAW264.7 cells could be significantly inhibited by fenofibrate in a dose-dependent pattern. Conclusions: Topical application of fenofibrate suppressed the formation of ocular surface squamous metaplasia, which might be mediated through the PPAR-α signaling pathway.

Research on circadian clock genes in non-small-cell lung carcinoma.

Circadian clock genes have become a hot topic in cancer research in recent years, and more and more studies are showing that clock genes are involved in regulating cell proliferation cycle and apoptosis of malignant tumors, neuroendocrine and immune function, and other processes. Lung cancer is a malignant tumor with increasing incidence worldwide. The pathogenesis of lung cancer is extremely complicated and includes genetic factors, living environment, and smoking, and the occurrence of lung cancer is related to the regulation of many oncogenes and tumor suppressor genes. But there are few studies on clock genes in lung cancer. Studies on clock genes may help to better understand the mechanism of lung cancer development for an improved treatment. The expressions of all 14 kinds of clock genes in adenocarcinoma (ADC) and squamous cell carcinoma (SCC), two main kinds of non-small-cell lung cancer (NSCLC), were studied based on integration and analysis of data from The Cancer Genome Atlas (TCGA) to show the association between clock gene expression and prognosis of cancer patients. Analysis of TCGA data indicated that overexpression of Cry2, BMAL1, and RORA with underexpression of Timeless and NPAS2 was associated with a favorable prognosis of ADC, and the expression of NPAS2 was associated with the time of patient survival. Additionally, the expression of Cry2 was related to TNM stage. In SCC, high expression of DEC1 was correlated with poor overall survival in patients and the expression of Timeless was associated with the time of patient survival. In NSCLC, circadian clock genes constitute cancer circadian rhythm by interacting with each other, showing that asynchrony with normal tissues, which collectively controlling the occurrence and development of NSCLC.

Research on circadian clock genes in common abdominal malignant tumors.

Circadian rhythm describes the 24-h oscillation in physiology and behavior of living organisms and presents a timing controller for life activity. Studies in recent years have reported that the abnormal expression of clock genes is closely related to the development of common abdominal malignant tumors. The expression of the 14 kinds of clock genes in 6 abdominal malignant tumors from Cancer Genome Atlas (TCGA) data was integrated and analyzed using R and Perl programming languages to show the association between clock gene expression and prognosis of cancer patients. Analysis of TCGA data indicated that the overexpression of Per1-3, Cry2, CLOCK, NR1D2 and RORA with underexpression of Timeless and NPAS2 was associated with a favorable prognosis in kidney cancer. In liver cancer, high expressions of Cry2 and RORA were correlated with prolonged overall survival (OS) in patients, while high expressions of NPAS2 and Timeless were correlated with a poor survival. High expression of CLOCK was positively correlated with OS in colon cancer patients. High expression of Cry2 and low expression of DEC1 were associated with a favorable prognosis in pancreatic cancer patients, respectively. Most of these clock-genes expressions were closely related to the clinical stage and degree of tumor differentiation of patients. Aberrant clock gene expression is related to the biological characteristics of abdominal malignant tumors, which likely has a causal role in cancer development and survival.

Peritumoral overexpression of ZBP-89 is associated with unfavorable disease-free survival rates in patients with hepatocellular carcinoma following hepatectomy.

Previous studies have revealed that the peritumoral environment has a profound influence on tumor initiation and progression. Zinc-binding protein-89 (ZBP-89) has been observed to be involved with tumor development, recurrence, and metastasis. High intratumoral expression of ZBP-89 has been associated with improved prognosis in several tumor types. However, the prognostic values of peritumoral expression of ZBP-89 remain to be elucidated in patients with hepatocellular carcinoma (HCC) following curative resection. In the present study, peritumoral ZBP-89 expression was examined using immunohistochemistry in 102 HCC patients who had received curative hepatectomy. Expression of ZBP-89 protein was positive in 66.3% of the peritumoral samples from 102 HCC patients. HCC patients with high peritumoral ZBP-89 expression exhibited significantly shorter disease-free survival (DFS) times (P=0.012) than those patients with low peritumoral ZBP-89 expression. Additionally, high ZBP-89 expression in peritumoral HCC tissue was positively associated with the presence of liver cirrhosis. Univariate and multivariate Cox proportional hazard regression analyses demonstrated that albumin levels ≤35 g/l, multiple tumors, tumor sizes ≥5 cm, and macroscopic vascular invasion may serve as independent prognostic factors for overall survival (OS) [hazard ratio (HR)=2.031; P=0.014] in patients with HCC. The multivariate Cox regression model identified that high ZBP-89 expression, multiple tumors and macroscopic vascular invasion were independent prognostic factors for shorter DFS durations. High expression of ZBP-89 in peritumoral HCC tissues was associated with a shorter DFS in HCC patients following curative hepatectomy. Additionally, high ZBP-89 expression in peritumoral HCC tissue was positively associated with the presence of liver cirrhosis in HCC patients, indicating that cirrhosis accompanied by high ZBP-89 expression may be a contributing factor to the poor prognosis of patients with HCC. Therefore, peritumoral ZBP-89 expression may be a good prognostic marker to predict DFS time in HCC patients following curative hepatectomy and may provide novel insights into the molecular mechanisms of HCC initiation.

Reversal of paclitaxel resistance in human ovarian cancer cells with redox-responsive micelles consisting of α-tocopheryl succinate-based polyphosphoester copolymers.

P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major obstacle in achieving the therapeutic benefits of paclitaxel (PTX) in the treatment of human ovarian carcinoma. This study is aimed to develop an efficient PTX drug delivery approach to overcome MDR. Redox-responsive micelles consisting of amphiphilic polymers containing disulfide linkages, ie, poly (phosphate ester)-SS-D-α-tocopheryl succinate (POPEA-SS-TOS, PSST) were prepared. PTX-loaded PSST micelles (PTX/PSST-M) designed to display synergistic functions, including reversible inhibition of P-gp, intracellular redox-sensitive release and potent anticancer activities. The average size of PTX/PSST-M was 68.1±4.9 nm. The encapsulated PTX was released quickly through redox-triggered dissociation of micelles. The inhibition of P-gp activity and enhanced cellular accumulation of the PSST micelles were validated. PTX/PSST-M showed significantly increased cytotoxicity against PTX-resistant human ovarian cancer A2780/PTX cells: when the cells were treated with PTX/PSST-M for 48 h, the equivalent IC50 value of PTX was reduced from 61.51 to 0.49 µmol/L. The enhanced cytotoxic effects of PTX/PSST-M against A2780/PTX cells were attributed to their synergistic effects on reducing the mitochondrial transmembrane potential, ATP depletion, ROS production, and activation of apoptotic pathways. Furthermore, PTX/PSST-M significantly increased cell apoptosis/necrosis and cell cycle arrest at the G2/M phase in A2780/PTX cells. These results demonstrate that the redox-responsive PSST micelles inhibit P-gp activity and have a good potential to effectively reverse PTX resistance in human ovarian carcinoma cells by activating intrinsic apoptotic pathways.