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PURPOSE. To determine if sleep deprivation induces dry eye through altering peroxisome proliferator-activated receptor alpha (PPARa) expression in mice. METHODS. The ''stick over water'' sleep deprivation-induced dry eye (SDE) model evaluated PPARa involvement in inducing this condition. Scanning electron microscopy (SEM) examined microvilli morphology in superficial corneal epithelial cells (SCECs) in SDE and PPARa À/À mice. Quantitative RT-PCR (qRT-PCR) and Western blot (WB) or immunostaining evaluated PPARa, carnitine palmitoyl transferase 1a (CPT1a), and transient receptor potential vanilloid 6 (TRPV6) expression levels and Ezrin phosphorylation status. Hematoxylin-eosin and Oil Red O staining characterized meibomian gland morphology and corneal lipid accumulation, respectively. Phenol red cotton threads measured tear production. In cultured corneal epithelial sheets, qRT-PCR, WB, and SEM determined the individual effects of fenofibrate and MK886 (PPARa agonist and antagonist, respectively) on PPARa, TRPV6 expression, and SCEC microvilli morphology. RESULTS. Corneal epithelial lipid accumulation, microvilli morphologic changes, and decreased tear production were associated with marked declines in PPARa, CPT1a, and TRPV6 expression levels as well as Ezrin phosphorylation status, whereas meibomian glands were unaltered in SDE mice. These effects of SDE mice mimicked those in their nonstressed PPARa À/À counterpart. Topical application of fenofibrate reversed these effects in SDE corneas. In cultured corneal epithelial sheets, fenofibrate increased PPARa and TRPV6 gene and protein expression levels and restored microvilli morphology, whereas MK886 attenuated these changes. CONCLUSIONS. Sleep deprivation induces dry eye through abnormal SCEC microvilli morphology, which is caused by sequential downregulation of PPARa, TRPV6 expression, and Ezrin phosphorylation status in mice.

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To determine the prognostic value of the number of positive lymph nodes (LNs) in cervical cancer and further stratify patients with positive LNs into multiple risk groups based on analysis of Surveillance Epidemiology and End Results (SEER) program. Patients with cervical cancer who undergo hysterectomy and had pathologically-confirmed positive LNs after lymphadenectomy were identified using the SEER database (1988-2012). Kaplan–Meier survival methods and Cox proportional hazards regression were performed. We included 2,222 patients with the median number of removed LNs and positive LNs was 22 and 2, respectively. Multivariable Cox analysis showed patients with > 2 positive LNs had poorer cause-specific survival (CSS) (hazard ratio [HR] 1.631, 95% confidence interval [CI] 1.382–1.926, P < 0.001) and overall survival (OS) (HR 1.570, 95% CI 1.346–1.832, P < 0.001) than patients with 1–2 positive LNs. Five-year CSS and OS were 78.9% vs. 65.5% (P < 0.001) and 76.7% vs. 62.7% (P < 0.001) for 1–2 positive LNs and > 2 positive LNs, respectively. The number of positive LNs had prognostic value in cervical squamous cell carcinoma or adenosquamous carcinoma, but not in cervical adenocarcinoma. The number of positive LNs is an independent risk factor for CSS and OS in cervical cancer. This new category might be helpful in better prognostic discrimination of node-positive early stage cervical cancer after hysterectomy.

Background: To investigate the differences of spontaneous functional connectivity (FC) of the primary visual cortex (V1) between patients with retinal vein occlusion (RVO) and healthy controls (HCs) using resting-state functional magnetic resonance imaging (rs-fMRI) data.Methods: Twenty-one patients with RVO in total (11 males, 10 females) and 21 HCs similarly analogue in age and sex background were enrolled and inspected with rs-fMRI. The difference in FC of V1 between two groups were compared using two-sample t-test. We used the receiver operating characteristic (ROC) curve to distinguish average FC values of RVO subjects from HCs. The interrelationships between FC signals of specific cerebrum regions and clinical features in RVOs were assessed with the Pearson's correlation analysis.Results: Compared with HCs, FC in left V1 and right middle frontal gyrus increased significantly in RVO group, while FC in left V1 and right cuneus decreased significantly. Meanwhile, patients with RVO presented increased FC between the right V1 and right middle frontal gyrus, right superior frontal gyrus, but declining FC between right V1 and right cuneus. The mean FC value between the right cuneus and the right V1 as well as the left V1 were negative correlated with the foveal thickness of RVO patients. ROC curve analysis of each brain regions showed the accuracy of AUC was excellent.Conclusions: RVO involves aberrant FC in V1 in different brain areas including visual-related and cognitive-related region, which might assist to unveil the underlying neural mechanisms of impaired visual function in RVO.

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Background: Moyamoya disease (MMD) is a chronic progressive cerebrovascular abnormality characterized by chronic occlusion of large intracranial vessels with smoky vascular development at the base of the skull. In patients with MMD, abnormal spontaneous brain activity would be expected.Purpose: To assess the brain activity changes in patients with MMD by resting-state functional MRI (rs-fMRI), using the percent amplitude of fluctuation (PerAF) analysis method.Materials and Methods: A total of 17 patients with MMD (3 males and 14 females) and 17 healthy control (HC) subjects with matched gender and age were recruited for this study. We used rs-fMRI to scan all the patients with MMD. Spontaneous neural activity was evaluated using the PerAF approach. The receiver operating characteristic (ROC) curve analysis was used to assess the ability of the PerAF to distinguish patients with MMD from HCs. The Hospital Anxiety and Depression Scale (HADS) tests were performed to assess the emotional status of patients with MMD and retinal nerve fiber layer thickness (RNFLT) was measured using high-resolution optical coherence tomography (hr-OCT). The relationship between the HADS scores, RNFLT values, and the PerAF signals was assessed using the Pearson's correlation analysis.Results: Compared with HCs, the PerAF signals in patients with MMD were decreased in the Frontal_Sup_Medial_R and Precentral_L, whereas those in the Caudate_L were increased. The areas under the ROC curves indicated that signals in these brain regions could distinguish between patients with MMD and HCs. The PerAF value of Frontal_Sup_Medial_R was positively correlated with the left and right eye RNFLT values and negatively correlated with the HADS scores.Conclusion: In patients with MMD, reduced PerAF signals in the Frontal_Sup_Medial_R, Precentral_L, and Caudate_L may be associated with psychiatric diseases including anxiety and depression and decreased RNFLT may be associated with ophthalmic complications due to the compression of terminal branches of the internal carotid artery in the retinal fiber layer. The PerAF can be used as an effective indicator of ocular complications of MMD and to study the neural mechanism underpinning emotional complications in patients with MMD.

Objective: To investigate the association of meibomian gland dysfunction (MGD) and ocular surface exposure with tear film instability in untreated thyroid eye disease (TED) patients. Methods: A cross-sectional study of TED patients from September 2020 to September 2022 was conducted. Ocular surface parameters included ocular surface disease index (OSDI), tear meniscus height (TMH), non-invasive tear break-up time (NITBUT), partial blinking rate, lipid layer thickness (LLT), meibomian gland dropout (meiboscore), Schirmer’s test, and corneal punctate epithelial erosions (PEE). Ocular surface exposure was assessed by the margin reflex distances of the upper and lower eyelid (MRD1 and MRD2), the amount of exophthalmos, lateral flare, and lagophthalmos. Results: In total, 152 eyes from 76 TED patients (64 females and 12 males, age 42.99 ± 12.28 years) and 93 eyes from 61 healthy controls (51 females and 10 males, age 43.52 ± 17.93 years) were examined. Compared with control eyes, TED eyes had higher OSDI, TMH, LLT, and PEE; shorter NITBUT; and worse meiboscore (all p < 0.05). They also had larger amounts of exophthalmos, longer MRD1, more lateral flare, and lagophthalmos. Multivariate analysis identified an association of the tear film instability with lagophthalmos (β = −1.13, 95%CI: −2.08, −0.18) and severe MGD in the lower eyelid (β = −5.01, 95%CI = −7.59, −2.43). Conclusions: Dry eye in TED is mainly manifested as evaporative dry eye disease. Severe lower eyelid MGD and worse lagophthalmos were significantly associated with tear film instability in treatment-naive TED patients.