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.

In recent years, with the rapid development of Chinese domestic surgical robot technology and the expansion of the application market, the "industry-university-research-medicine" collaborative innovation transformation mode has gradually developed and formed. Medical institutions play an important role in multi-party cooperation with enterprises, universities, and research institutes, as well as in product planning, technology research and development, achievement transformation, and personnel training. On the basis of reviewing the current situation of the development of the "industry-university-research-medicine" collaborative innovation transformation mode of domestic surgical robots, this study explores the multiple roles played by medical institutions in this mode and challenges, further putting forward corresponding recommendations.
Humans ; Robotics ; Universities ; Medicine ; Industry ; Technology

Objective To observe the effect and toxicity of gemcitabine and S-1 in treatment of metastatic triple-negative breast cancer.Methods In this study,41 cases of metastatic breast cancer were treated in the General Hospital of Shenyang Military Region between Jun.2010 and Dec.2012.The median age was 55 years old.The pathological diagnosis of these patients was triple-negative breast cancer.All patients were given gemcitabine 1000 mg/m2 intravenously on the 1st and 8th day,and 60 mg S-1 from the 1st day to the 14th day orally for every cycle.There were 21 days for each cycle.All patients accepted at least 2 cycles of chemotherapy and once effect evaluation.Results 41 cases were diagnosed as metastatic triple-negative breast cancer,with the failure of second-line treatment.The median age was 55 years.All cases were followed up until death.All the 41 cases were administrated for more than 2 cycles,among whom,there were 0 case of complete response(CR),16 cases (39.0％)of partial response(PR),14 cases(34.1％) of stable disease(SD),and 11 cases(26.8％) of progressive disease(PD).The disease control rate was 73.1％ (30/41).In this study,median progression free survival(mPFS)was 7.9 months.The rate of digestive toxicity and marrow suppression was 24.4％ and 55％ respectively.No patient stopped treatment because of severe toxicities.Conclusion The chemotherapy regimen of gemcitabine and S-1 is effective in treatment of metastatic triple-negative breast cancer,and the toxicity could be tolerated.

Objective To study the relationship between facial skin conditions and TCM constitutional types; To provide new means and methods for guidance of skin conservation and skin health improvement from the aspect of constitutional types. Methods Totally 2241 female volunteers in nine provincial capital cities and municipalities participated in this research, and were investigated by web questionnaire. Constitutional types were determined according to the“Classification and Judgment of TCM Constitutional Types”standard issued by China Association of Chinese Medicine. Skin color, glossiness, delicate degree, moistness, firmness, resilience, uniformity and other indicators were scored. Skin conditions were classified into three groups:1-3 score group, 4-6 score group, and 7-9 score group, and the constitutional differences among each group were compared. Results Yang-deficiency and mild constitutional types accounted for the largest proportion. Yellowish skin color accounted for the largest proportion, and the next were white, dark and reddish. Yang-deficiency constitutional type accounted for the largest proportion in 1-3 score group, and the second was Qi-stagnation; Yang-deficiency and mild constitutional types accounted for the largest proportion in 4-6 score group; mild constitutional type accounted for the largest proportion in 7-9 score group. Conclusion People with mild constitutional type got highest score in every skin index, while biased constitutional types influenced the score in varied degrees. The constitutional types which influenced Chinese urban females’ facial skin index more were Yang-deficiency and Qi-stagnation constitutional types.

In order to obtain enough fusion protein for developing preclinical studies of IFNbeta-HAS, we screened Pichia pastoris transformants expressing high-level protein by immunology method. The yield of IFNbeta-HSA was about 500 mg/L by fed-batch fermentation. The purity of IFNbeta-HSA reached 96% through the steps of ultrafiltration, Blue Sepharose FF, Ni2+-IMAC and DEAE Sepharose FF. Analysis of Western blotting showed that IFNbeta-HSA had the antigenicity of IFNbeta and HSA. The specific activity was about 1.96 x 10(7) IU/mg by standard survival activity test on WISH cells challenged with VSV virus. This study provided a method to produce IFNbeta-HSA.
Fermentation ; Humans ; Interferon-beta ; biosynthesis ; genetics ; Pichia ; genetics ; metabolism ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; isolation & purification ; Serum Albumin ; biosynthesis ; genetics

Objective To ascertain clinical experience and toxic reactions of treating NSCLC by Gefitinib(Iressa).Methods Clinical data of 51 NSCLC cases were collected and analyzed who were treated with Iressa from Mar.2004 to Mar.2006.Evaluations were made about curative effects,quality of life,mean survival time,time to progression and toxic reactions.Results Fifty-one patients were all followed up.Total mitigative rate of the focus was 29.4%,total control rate was 66.7%,and alleviative rate of clinical symptoms was 62.7%.The difference of KPS grades in 4 weeks was significant.Mean survival time of all the patients was 8.2 months.Time to progression was 6.1 months.Ⅲ~Ⅳ grades of toxic reaction were not found.Conclusion Gefitinib may obviously improve the clinical symptom and QOL of the NSCLC patients,and it has good tolerance to treat NSCLC.It is a kind of molecule-target medicine suited with Chinese.