Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Infectious keratitis (IK) is a leading cause of blindness worldwide, primarily resulting from improper contact lens use, trauma, and a compromised immune response. The pathogenic microorganisms responsible for IK include bacteria, fungi, viruses, and Acanthamoeba. This review examines standard therapeutic agents for treating IK, including broad-spectrum empiric antibiotics for bacterial keratitis (BK), antifungals such as voriconazole and natamycin for fungal infections, and antiviral nucleoside analogues for viral keratitis (VK). Additionally, this review discusses therapeutic agents, such as polyhexamethylene biguanide (PHMB), for the treatment of Acanthamoeba keratitis (AK). The review also addresses emerging drugs and the challenges associated with their clinical application, including anti-biofilm agents that combat drug resistance and nuclear factor kappa-B (NF-κB) pathway-targeted therapies to mitigate inflammation. Furthermore, methods of Photodynamic Antimicrobial Therapy (PDAT) are explored. This review underscores the importance of integrating novel and traditional therapies to tackle drug resistance and enhance drug delivery, with the goal of advancing treatment strategies for IK.

Microfluidic chip or lab-on-a-chip is a multidisciplinary cross-technology. Among them, organ-on-a-chip technology enables precise regulation of cells and microenvironment at micron level.This tecnology is expected to simulate in vivo human physiology and overcome the shortcomings of traditional animal models and cell culture techniques.In ophthalmology, organ-on-a-chip models are primarily focused on creating biomimetic models of the cornea, retina and posterior chamber to study diseases such as dry eye, glaucoma, age-related macular degeneration and diabetic retinopathy.In addition, continuous monitoring and real-time diagnosis of tear and intraocular fluid biomarkers using microfluidic chips have become a current research hot topic.The microfluidic chips also have a wide range of applications in drug analysis, drug development, and drug screening.This article reviews the recent progress and shortcomings of microfluidic chip in in vitro model construction, point-of-care testing and drug development, and discusses its future development in ophthalmology.

We investigated whether FTY-720 might have an effect on bleomycin-induced pulmonary fibrosis through inhibiting TGF-β1 pathway, and up-regulating autophagy. The pulmonary fibrosis was induced by bleomycin. FTY-720 (1 mg/kg) drug was intraperitoneally injected into mice. Histological changes and inflammatory factors were observed, and EMT and autophagy protein markers were studied by immunohistochemistry and immunofluorescence. The effects of bleomycin on MLE-12 cells were detected by MTT assay and flow cytometry, and the related molecular mechanisms were studied by Western Blot. FTY-720 considerably attenuated bleomycin-induced disorganization of alveolar tissue, extracellular collagen deposition, and α-SMA and E-cadherin levels in mice. The levels of IL-1β, TNF-α, and IL-6 cytokines were attenuated in bronchoalveolar lavage fluid, as well as protein content and leukocyte count. COL1A1 and MMP9 protein expressions in lung tissue were significantly reduced. Additionally, FTY-720 treatment effectively inhibited the expressions of key proteins in TGF-β1/TAK1/P38MAPK pathway and regulated autophagy proteins. Similar results were additionally found in cellular assays with mouse alveolar epithelial cells. Our study provides proof for a new mechanism for FTY-720 to suppress pulmonary fibrosis. FTY-720 is also a target for treating pulmonary fibrosis.

Ocular surface inflammatory disorder (OSID) is a chronic ocular disease caused by systemic disorders or involving the local immune system.OSID induces persistent inflammatory reaction in the ocular adnexal connective tissues which in turn give rise to tear hypertonicity and ocular surface epithelial damage, leading to dry eye formation or progression.Common immune-related ocular surface diseases include vernal keratoconjunctivitis, Sj?gren syndrome, graft versus host disease, dry eye and immune-related corneal disease, all of which can significantly impact the visual function and quality of life of patients.Current treatments including the use of artificial tears and glucocorticoid eye drops are not always effective and have the risk of adverse events.Cyclosporine A (CsA) is a commonly utilized immunosuppressant that has a strong immunomodulatory effect, but its clinical application is somewhat limited due to the low permeability of its current ophthalmic dosage form.The development of CsA ophthalmic agents has changed the treatment strategy for OSID.The development of 0.1% CsA cationic emulsion has significantly improved the efficacy and safety of topical CsA treatment, which is worth the attention.In order to rationally apply 0.1% CsA cationic emulsion to OSID, ophthalmologists should fully understand the immune-related pathogenesis of each OSID and comprehend the curative effect, indication, application methods and adverse events of topical CsA treatment.

Objective:To evaluate the efficacy and safety of a China original liquid pulsation system for the treatment of meibomian gland dysfunction (MGD).Methods:A non-randomized controlled clinical trial was conducted.Twenty-two patients (44 eyes) diagnosed with MGD in Eye and ENT Hospital of Fudan University from February to August 2022 were enrolled.The patients were assigned into two groups according to their willingness.Of the 22 patients (44 eyes), 10 patients (20 eyes) in single liquid pulsation system group were treated with single liquid pulsation system for 12 minutes, and 12 patients (24 eyes) in intense pulsed light (IPL) group were treated with a course (4 times) of IPL, warm compresses and meibomian gland massage at three-week intervals.There was no difference in age and other baseline clinical indexes between the two groups (all at P<0.05). The meibum grading, quality grading of tear film lipid layer, Symptom Assessment Questionnaire in Dry Eye (SANDE) questionnaire score, first and average tear breakup time (BUT), corneal fluorescein sodium staining (CFS) score, tear meniscus height (TMH), and the area of meibomian gland loss were determined at baseline, 1 and 3 months after treatment.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Eye and ENT Hospital of Fudan University (No.2021069). Written informed consent was obtained from each patient before any medical examination. Results:Statistically significant group effects and time effects were found in the quality of tear film lipid layer ( Hgroup=4.39, P=0.036, Htime=6.30, P=0.043) and average BUT ( Fgroup=4.41, P=0.038; Ftime=4.08, P=0.049) in the two groups.The meibum grading, first BUT and TMH 1 and 3 months after treatment were significantly better than before treatment in single liquid pulsation system group (all at P<0.05). Compared with before treatment, there was no significant improvement in the meibum grading, distribution of tear film lipid, first BUT and TMH at 1 and 3 months after treatment in IPL group (all at P>0.05). In both groups, the SANDE and CFS scores 1 and 3 months after treatment were better than those before treatment, showing statistically significance (all at P<0.05). In terms of safety, neither instrument-related adverse events nor extra complaints of discomfort were reported in the single liquid pulsation system group.In both groups, the number of patients with positive CFS staining significantly decreased, and no new cases with positive CFS appeared after treatment. Conclusions:This China original liquid pulsation system is a safe and effective physical therapy in improving tear film dysfunction and ocular surface symptoms of MGD patients within 3 months after treatment.

Hand, foot and mouth disease (HFMD) is a widespread infectious disease mainly affecting children aged five and under. In China, the current epidemic situation of HFMD remains severe, with a persistently high and increasing incidence rate, causing a substantial disease burden. A monovalent vaccine against Enterovirus A71 (EV-A71), the most common cause of severe and fatal HFMD cases, has been available in China since 2016. Although randomized controlled trials established the vaccine's efficacy among research subjects, this may not reflect the impact under "real world" conditions in the general population. Therefore, based on a systematic literature search, this paper comprehensively reviewed and analyzed relevant studies based on real-world data and collected real-world evidence about the EV-A71 vaccine on the controlling HFMD incidence. It was found that the real-world study of the EV-A71 vaccine on HFMD was few; most were limited to a province or city; there is no study comprehensively considered other important influencing factors in addition to immunization, such as temperature, relative humidity, the age structure of the population, gross domestic product, etc. The progress of using real-world data to study the impact of the EV-A71 vaccine on HFMD reviewed in this study is helpful to have a clear and comprehensive understanding of the status quo and will provide guidance and reference for future studies to assess the short-term and long-term effects of EV-A71 vaccine and other vaccines.

Objective:To design a replaceable corneal scaler and explore its effect on improving the positive detection rate of corneal bacteria and the cure rate of patients with infectious keratitis.Methods:Totally 100 patients with infectious keratitis treated in the Eye&Ent Hospital of Fudan University in Shanghai from June 2020 to October 2021 were conveniently selected as the application object, 50 patients from June 2020 to January 2021 were selected as the control group, and 50 patients from February 2021 to October 2021 were selected as the experimental group. The control group used the traditional corneal scalpel for corneal scraping, and the experimental group used the replaceable corneal scalpel for corneal scraping. The positive detection rate of bacteria, the cure rate of patients as of the date of data collection, the comfort status of patients and the operation difficulty score of medical staff were compared between the two groups.Results:The 28 cases (56%) were positive in the experimental group, and 30 cases (60%) were cured as of the date of data collection; 16 cases (32%) were positive in the control group and 18 cases (36%) were cured as of the date of data collection. The difference between the two groups was statistically significant ( χ2=-2.47, -2.20, all P<0.05). The score of comfort in the experimental group was (83.92 ± 6.40) and that in the control group was (54.04 ± 10.69). The difference between the two groups was statistically significant ( t=17.14, P<0.01). The operation difficulty score of medical staff in the experimental group was (1.46 ± 0.54) and that of medical staff in the control group was (3.24 ± 0.72). The difference between the two groups was statistically significant ( t=-13.50, P<0.01). Conclusions:The use of replaceable corneal scalpel can not only improve the positive detection rate of patients, improve the treatment effect of patients, improve the comfort and satisfaction of patients, but also improve the work efficiency of medical staff and reduce the operational risk of medical staff, so as to improve the real professional value of medical staff.

Dry eye is becoming more common worldwide.Its pathophysiology is complicated, and its condition is chronic.Treatment options of dry eye are ineffective.As a multifactorial ocular surface disease, tear film instability, tear hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities resulted from various causes are main natural pathological processes of dry eye.This multifactorial process of the disease leads to poor efficacy of single anti-inflammatory therapy.Oxidative stress is closely related to the occurrence of dry eye.During the decrease of tear film stability, reactive oxygen species produced by oxidative stress system damage the myelin sheath of ocular nerve and the lipid layer of tear film, inducing or aggravating the ocular inflammatory response.Targeting the main causes of dry eye's pathogenesis, stopping the vicious cycle of inflammatory responses in each link, and relieving patients' conditions are the main goals of antioxidant therapy.The development of anti-inflammatory and antioxidant medications is currently the main focus of international research on novel anti-dry eye medications.Some progresses have been made in the area of targeting oxidative stress biomarkers, mitochondrial targeting medications, mucin secretion, antioxidant enzymes like glycoprotein selenium and lactoferritin, as well as multifunctional nanoagents, and the antioxidant eye drops using nanomaterials have more advantages.Antioxidant treatment may be one of the potential future avenues of dry eye clinical research.Ophthalmologists and researchers should be fully aware of, pay close attention to and actively participate in investigations that are relevant to dry eye antioxidant therapy and the development of new medications.

Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by various enteroviruses. China has the most significant number of reported cases and deaths of HFMD over the globe. Understanding the epidemic laws of HFMD can provide a scientific basis for designing prevention and control measures. The dynamic transmission models focus on the transmission mechanism of infectious diseases. They can simulate the actual situation to study the epidemic rules of diseases by adding, deleting, and subdividing compartments. More researchers have paid attention to dynamic models because of their high flexibility. To carry out the dynamic model of the HFMD research more effectively, a comprehensive understanding of related research progress in this field is deeply needed. In this paper, based on various researchers' different research purposes of dynamic models, the research progress was classified and summarized, providing meaningful guidance for model construction methods and future research directions and references for dynamic modeling of other models of infectious diseases. It was found that most studies used the SIR dynamic model or its extended model (such as the SEIR model), and few studies contained a complex factor compartment. Some important epidemiological parameters (such as R0) were obtained by studying the HFMD cases in a specific region, simulating different intervention scenarios to evaluate the effect of measures, or revealing the future trend by model prediction. However, there is no dynamic model simultaneously considering age structure, population moving, seasonality and periodicity, and vaccination.