PPARγ: the dominant regulator among PPARs in dry eye lacrimal gland and diabetic lacrimal gland

AIM: To determine whether lectin-like ox-LDL receptor (LOX-1) regulates adhesion molecules expression and neutrophil infiltration in A. fumigatus keratitis of C57BL/6 mice.METHODS: C57BL/6 mice were pretreated with a neutralizing antibody to LOX-1 (5 μg/5 μL) or control nonspecific IgG (5 μg/5 μL), LOX-1 inhibitor Poly-I (2 μg/5 μL) or PBS by subconjunctival injection. Fungal keratitis mouse models of C57BL/6 mice were established by scraping corneal central epithelium, smearing A. fumigatus on the corneal surface and covering the eye with contact lenses. The corneal response to infection was assessed via clinical score. The mRNA levels of the adhesion molecules ICAM-1, VCAM-1, P-selectin and E-selectin were tested in control and infected corneas by RT-PCR. The protein levels of ICAM-1 were evaluated by immunofluorescence (IF) and Western blot. Neutrophils were extracted from the abdominal cavity of C57BL/6 mice followed by pretreatment using antibody to LOX-1 (10 μg/mL) or control nonspecific IgG (10 μg/mL), the Poly-I (4 μg/mL) or PBS. The cells were then stimulated with A. fumigatus and tested mRNA and protein levels of LFA-1 using RT-PCR and Western blot. IF and myeloperoxidase (MPO) assays were used to assess neutrophil infiltration in mice corneas.RESULTS: Pretreatment of LOX-1 antibody or the Poly-I reduced the degree of inflammation of cornea and decreased the clinical fungal keratitis score compared with pretreatment of IgG or PBS. And these pretreatment also displayed an obvious decline in the mRNA levels of ICAM-1, VCAM-1, P-selectin, E-selectin and LFA-1 expression compared with control groups . Furthermore, pretreated with LOX-1 antibody or Poly-I, the protein levels of ICAM-1 and LFA-1 also decreased compared with control groups. Neutrophil infiltration in the cornea was significantly reduced after pretreatment of LOX-1 antibody or Poly-I compared with control groups by IF and MPO assays. CONCLUSION: These data provide evidence that inhibition of LOX-1 can decrease the expression of adhesion molecules and thus reduce neutrophil infiltration in A. fumigatus infected corneas of C57BL/6 mice.     

横断面研究能否进行因果推断

基于变量调查(或测量)的共时性、统计学关联及幸存者偏倚等原因,横断面研究被认为不能进行因果推断,这是当前的"共识"。本文基于因果思维,借助因果图,首先明确定义真实截面和测量截面,并识别截面概念仅存在于理论的特性。实际横断面研究中,测量变量的共时性并不存在,而是无一例外地表现为非共时性时序,其实质上相当于测量变量间互为独立性假设,或不存在有差别错分偏倚。类似于累积病例对照研究和历史性队列研究,横断面研究均为暴露和结局已存在或发生后进行的测量,这种测量相当于对变量值的历史重建或"考古"。这类研究进行因果推断的共性前提条件之一是,测量变量与其历史变量间必须存在着因果律。测量变量均为真实变量的替代者,测量变量间的时序在因果推断上并不重要。应加强对横断面研究分析性角色的认识。     

Association between vitiligo and subsequent risk of dementia: A population‐based cohort study

Increasing evidence suggests a positive association between autoimmune disorders and the subsequent risk of dementia, supporting the idea that neuroinflammation is a major contributor to dementia. However, whether or not adults with vitiligo have an increased risk of dementia remains unclear. We aimed to investigate the association between vitiligo and the subsequent risk of dementia. A total of 1320 patients with vitiligo and 5280 matched controls were identified from the Taiwan National Health Insurance Research Database between 1998 and 2011. Dementia was diagnosed by board‐certificated psychiatrists or neurologists in the follow‐up period. Cox proportional hazards models were used to estimate the adjusted hazard ratios (aHR) after controlling for age, sex, income‐related monthly premium, residence and comorbidities associated with dementia. The incidence rate of dementia (per 100 000 person‐years) was 502.8 among patients with vitiligo and 101.9 among the controls. Patients with vitiligo were more likely to develop any type of dementia (aHR, 5.30; 95% confidence interval [CI], 3.30–8.51), Alzheimer’s disease (aHR, 12.22; 95% CI, 3.71–40.28) and vascular dementia (aHR, 3.99; 95% CI, 1.31–12.15) compared with the controls. In conclusion, middle‐aged and old patients with vitiligo are more likely to develop dementia compared with those without vitiligo. This novel finding reminds physicians to be more careful about signs of dementia when managing patients with vitiligo and provides the basis for further investigations that clarify the underlying mechanisms.     

The worldwide coronavirus disease 2019 outbreak: Advice and recommendation on radiology management and infection control from makeshift hospitals in Wuhan

To describe and advise on management protocols and infection-protection experience of the radiology department in makeshift hospitals in Wuhan during the coronavirus disease 2019 (COVID-19) outbreak.Based on the literature review and the experience in the frontline, we retrospectively reviewed the configuration of the radiology department, human resource, personal protection, examination procedures for patients confirmed with COVID-19 in Wuhan fangcang shelter hospital.From February 11, 2020 to March 10, 2020, 2730 and 510 CT examinations were performed in the Hanjiang shelter hospital and Hanyang Sports School shelter hospital, respectively, including initial examinations and re-examinations. The maximum number of daily CT examinations reached 289. The CT scanned a patient approximately once every 13 mins.Fangcang shelter radiology department could be powerful components of both global and national responses to the COVID-19 pandemic.     

Development of a Novel Formulation with Hypericin To Treat Cutaneous Leishmaniasis Based on Photodynamic Therapy in In Vitro and In Vivo Studies

An evaluation of the leishmanicidal activity in vitro and in vivo of hypericin, an expanded-spectrum photosensitizer found in Hypericum perforatum, is presented. Hypericin was evaluated against intracellular amastigotes in vitro of Leishmania (Viannia) panamensis. A topical formulation containing 0.5% hypericin was developed and assayed in vivo in a hamster model of cutaneous leishmaniasis. Results demonstrate that hypericin induces a significant antiamastigote effect in vitro against L. panamensis by decreasing the number of parasites inside infected cells. The topical formulation of 0.5% hypericin allows healing of L. panamensis-induced lesions upon a topical application of 40 mg/day plus visible-light irradiation (5 J/cm², 15 min), twice a week for 3 weeks.