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 .

Objective To evaluate the pharmacokineties of ropivacaine for single sciatic nerve block in dogs.Methods Twelve healthy adult mongrel dogs weighing 14-17 kg were randomized to receive 0.5% ropivaeaine 10 mg/kg or 20 mg/kg for single sciatic nerve block(n=6 each).ECG,BP and HR were monitored and recorded during anesthesia.Blood samples were obtained from femoral artery before ropivacaine injection (baseline)and at 10,20,30,40,60,90,120,150,180,240,360 and 720 min after ropivacaine injeetion for determination of plasma ropivaeaine concentration(by reversc-phasc high performance liquid chromatography).Arterial blood samples were also taken when adverse reactions occurred.The pharmacokinetic parameters were eMeulated with DAS 1.0 software package.Results The concentration-time curve of ropivacaine for single sciatic nenre block was fitted to two-compartment open model in both groups.The peak plasma concentration of ropivaeaine was significantly lower in 10 mg/kg group than in 20 mg/kg group.Two dogs developed convulsion in 20 mg/kg group.The plasma ropivaeaine concentration was 12.56 and 13.67 mg/L respectively during convulsion.Conclusion Pharmaeokinetic profile of ropivaeaine for single sciatic nerve block is best described by two-compartment model.Bopivaeaine 20 mg/kg for sciatic nerve block can hardly be tolerated by dogs.

After first report of local anesthetics on cardiac toxicity was published in 1979, A lot of researches of local anesthetics on the mechanism of cardiac toxicity and its treatments were reported, and some advances were reviewed in this article during recent years.

Objectives To study if there exists the ununi formity of drug resistance of mycobacterium tuberculosis (M.TB) isolated from MDR-TB patients .Methods One MDR-TB patient was chosen for this study a nd his sputum was cultured.The suspension of the culture was filtered through 8 0?m -pore-size membrane filter and single M.TB suspension was obtained.The single M.TB suspension was cultured on Lowsenstein Jensen (L-J) medium.24 of col onies were obtained and they were cultured respectively again to get pure strain s.The drug sensitivity test was carried out for these 24 pure strains of M.TB wi th Chinese standard method.H 37 Rv was taken as control.Results 1 strain (4 2%) was found to be susceptive to INH,22 strains ( 91 6%) resistant to low concentration INH (H 1 ),1 strain (4 2%) resistant to high concentration INH (H 10 ).2 strains (8 3%) were found t o be susceptive to RFP,2 strains (8 3%) resistant to low concentration RFP(R 50 ),20 strains (83 4%) resistant to high concentration RFP(R 250 ).We f ound 1 strain (4 2%) susceptive to SM,23 strains (95 8%) resistant to high concentr ation SM(S 100 ).All were susceptive to EMB.Conclusions The ununiformity of drug resistance exists among the M.TB isolated from the MDR-TB patients.Sensitive and resistant strains exist together,low and high concentration-drug-resistant strains coexi st in the same situation.The majority of M.TB is drug-resistant and only a few are still sensitive to low concentration- drug- resistant.

AIM: To establish a Reversed-Phase high performance liquid chromatography method for determination of plasma ropivacaine in dog.METHODS:The sample was deproteinated by acetonitrile and determined with RP-HPLC and ultraviolet detection.the analytical column was Intertsil C18 column((4.6) mm?250 mm,5 ?m).The mobile phase consisted of methanol:H_2O(5050),the detection wavelength was 215 nm and the flow rate was(1.4)(ml?min~(-1)),the column temperature was 20 ℃,the sensitivity was 0.02AUFS respectively.The volume of sample for detection is 10 ?l.RESULTS:The linear range was(0.1)-25(?g?ml~(-1))(r=(0.9992)). The recovery of ropivacaine was(91.2)%-(93.6)%,RSD was(2.10)%-(3.40)%(n=6).The detection limit was(0.05)(?g?ml~(-1)).the intra-day and interday precisions of assay for ropivacaine was(1.35)%-(2.88)% and(1.80)%-(3.76)%.The quantative analysis of ropivacaine in plasma was not interfered by impurities.CONCLUSION: The assay method was shown to be suitable for determination the concentration of ropivacaine in plasma.The method is simple,accurate,sensitive and reproducible.

Aim To study the immunoregulatory effect of Mycobacterium vaccae vaccine on asthmatic guinea pig.Methods 30 guinea pigs were randomly divided into NS,asthma and Mycobacterium vaccae vaccine groups. A guinea pig model of asthma was formed with ovalbumin.Every guinea pig of Mycobacterium vaccae vaccine group was intramuscularly injected with 22.5 ?g Mycobacterium vaccae vaccine 10 days before ovalbumin immunization.mRNA expressions of IL-4,IL-5 and IFN-? in lung tissue,total IgE and ovalbumin-specific IgE in serum were determined. Results For Mycobacterium vaccae vaccine group guinea pigs, mRNA expressions(optical density value) of IL-4(0.060?0.018) and IL-5(0.052?0.006)in lung tissue were significantly lower than those of asthma group(0.111?0.025,0.106?0.030 respectively; both P