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.

Objective To study liquid based cytology test and its application values in the detection of fiber bronchoscopic aspi‐rates .Methods LBP sedimentation type of ThinPrep cell production system combined with the conventional smear were used to de‐tect 2000 specimens of fiber bronchoscopic aspirates ,and conduct microscope observation and cytological diagnosis .Results Based on liquid based cytology cell production method ,there were 614 positive cases (30 .7% ) ,267 cases of squamous cell carcinoma (13 .4% ) ,and 217 cases of adenocarcinoma(10 .9% ) ,83 cases of small cell carcinoma (4 .2% ) ,and 47 cases of undifferentiated car‐cinoma (2 .4% ) .The diagnostic sensitivity for lung cancer of liquid‐based cytology test was 64 .6% and conventional smear was 49 .2% .We also found 7 cases of fungus positive ,35 cases of typical caseous necrosis with liquid based cytology test .Conclusion The ThinPrep cell production has a more clean background ,more intact cell structure ,more efficient observation and increased posi‐tive rate of detection of cancer cells than the smears made by traditional methods .A combination of two methods can increase the accuracy of cytological detection of fiber bronchoscope aspirates and positive detection rate ,and also can assist the diagnosis of fungi and TB infections .