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 identify the occurrence and microorganism profile of device-associated healthcare-associa-ted infections (DA-HAIs)in the intensive care unit (ICU)of a university hospital in China.Methods From Janua-ry 1 to November 30,2015,patients admitted to the ICU of a university hospital in China for more than 48 hours were performed prospective descriptive study. DA-HAIs were defined according to the criteria of the Centers for Disease Control and Prevention (CDC)of U.S.,descriptive statistical analysis was performed.Results Of 254 pa-tients admitted to ICU,the overall incidence of DA-HAIs was 15.35% ,with 10.23 cases of DA-HAIs per 1 000 ICU-days;the incidence of ventilator-associated pneumonia (VAP ),catheter-associated urinary tract infection (CAUTI),and central line-associated bloodstream infection (CLABSI)were 7.05 per 1 000 ventilator-days,4.91 per 1 000 urinary catheter-days,and 3.22 per 1 000 central line-days,respectively. The main infection site was lower respiratory tract,accounting for 48. 27% ,followed by bloodstream system (27. 59% ),urinary tract (22.99% ),and gastrointestinal tract(1.15% ). The major isolated microorganism was Acinetobacterbaumannii (21 .52% ).Conclusion The surveillance system can identify the epidemiological status of DA-HAIs and make effec-tive control measures to ensure the healthcare safety.

Objective To investigate the invasion situation of cardinal ligaments(CL) in stage Ⅰ A2 - ⅡA2 cervical cancer and to find the high risk clinicopathological factors affecting its invasion .Methods The retrospective analysis was performed on the clinicopathological data in 2 982 patients with cervical cancer treated by operation extracted in 5 hospitals from January 2004 to De‐cember 2014 .Results (1) Totally 855 cases according with the research condition were included .The CL invasion was found in 20 cases(2 .3% ) .No CL invasion occurred in the stage ⅠA2 ,the CL invasion rate in the stage ⅠB1 was 1 .7% ,in the stage ⅠB2 was 1 .2% ,in the stage ⅡA1 was 5 .7% and in the stage ⅡA2 was 2 .9% .With the increase of FIGO staging ,the CL invasion rate had no significant increase(P=0 .269) .(2) The infiltration rate of left CL and right CL had no statistical difference among the stageⅠA2- ⅡA2(P=1 .000) .And the invasion rate of the left CL with different FIGO stages had no statistical difference(P=0 .286) , while the right one had statistical difference(P=0 .005) ,in which the highest was in the stage ⅡA1 (4 .3% ) .(3)The univariate a‐nalysis found that lymph‐vascular invasion ,cervical stroma infiltration depth ,pelvic lymph node metastasis ,uterus body infiltration and vaginal fornix infiltration were the risk factors of CL invasion(P<0 .01);the further multivariate analysis determined that the invasion of uterine body(OR=11 .858) ,pelvic lymph node metastasis(OR=6 .359 ,) ,vaginal fornix infiltration(OR=6 .012 ,) were the risk factors for CL invasion(P<0 .05) .Conclusion The invasion rate of CL invasion in early stage cervcial cancer is low .The invasion of uterine body ,pelvic lymph node metastasis and vaginal fornix filtration are the risk factors for CL invasion in the stageⅠA2- ⅡA2 cervical cancer .