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 analyze the morphology and molecular biology of Rhodococcus erythropolis isolated from blood culture, and clarify its microbiological characteristics, clinical diagnosis and treatment. Methods:Strain F1069 was isolated and cultured. Then, it was analyzed by morphology, physiological tests, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS), 16S rRNA gene sequencing, and whole-genome sequencing analysis.Results:The colonies of Rhodococcus erythropolis were light yellow, moist, round, and raised, and had neatly-edged margins after being cultured for 48 h. They could turn orange-red after a prolonged cultivation time. The strain was gram-positive bacillus without spores and was negative in acid-fast staining. The strain was identified as Rhodococcus erythropolis by MALDI-TOF MS, and the result was confirmed by 16S rRNA gene sequencing. The F1069 strain contained the RbpA resistance gene and multiple virulence genes. Conclusions:Cases of Rhodococcus erythropolis infection are rare. The diagnosis of such cases depends on the pathogen detection results, especially molecular biology methods. A definitive diagnosis enables rapid guidance for clinical anti-infection treatment.

Objective:To analyze the morphology and molecular biology of Rhodococcus erythropolis isolated from blood culture, and clarify its microbiological characteristics, clinical diagnosis and treatment. Methods:Strain F1069 was isolated and cultured. Then, it was analyzed by morphology, physiological tests, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS), 16S rRNA gene sequencing, and whole-genome sequencing analysis.Results:The colonies of Rhodococcus erythropolis were light yellow, moist, round, and raised, and had neatly-edged margins after being cultured for 48 h. They could turn orange-red after a prolonged cultivation time. The strain was gram-positive bacillus without spores and was negative in acid-fast staining. The strain was identified as Rhodococcus erythropolis by MALDI-TOF MS, and the result was confirmed by 16S rRNA gene sequencing. The F1069 strain contained the RbpA resistance gene and multiple virulence genes. Conclusions:Cases of Rhodococcus erythropolis infection are rare. The diagnosis of such cases depends on the pathogen detection results, especially molecular biology methods. A definitive diagnosis enables rapid guidance for clinical anti-infection treatment.

Objective:To optimize the preparation process of Qinggan Liangxue Granules.Methods:The L 9 (3 4) orthogonal experimental design was used to investigate the effects of water addition, extraction time and extraction times on the extraction process of Qinggan Liangxue Granules by taking the transfer rate of astilbin and paeoniflorin as the indexes, so as to screen the optimal extraction process. The evaluation indexes of granule molding rate, water content, solubility and fluidity were used to compare the effect of finished products under different ratios of excipients and granulation conditions. Results:The optimal extraction process was to add 10 times the amount of water reflux extraction twice, each time 1.5 h; using wet granulation, the ratio of dry paste powder to base material was 4:1 ( m/ m), and the wetting agent was 95% ethanol. Conclusion:The preparation process of Qinggan Liangxue Granules is stable and feasible, which lays a foundation for further research and development and quality control.

Objective To investigate the methods and effect of the dual incision lock type golf combined with support plate in the treatment of tibial plateau fracture.Methods 80 cases with comminuted fracture of the tibial plateau were randomly divided into two groups.40 cases in the observation group were given the dual incision lock type golf combined with support plate.and the control group used traditional single incision T-shaped steel treatment.The clinical efficacy was compared between the two groups.Results 80 patients were followed up.Excellent rate of the observation group was 67.5％,which was significantly higher than 45.0％ of the control group.The incidence rate of complication in observation group was 2.5 ％,which was significantly lower than 22.5 ％ in the control group (P ＜ 0.05).The reset extent of patients,healing time,loading time,HSS score of the observation group were significantly better than those of the control group (P ＜ 0.05).Conclusion The dual incision lock type golf combined with support plate in the treatment of tibial plateau fracture has less trauma,reliable fixation,early functional exercise andfewer complications.

Objective To observe the clinical effects of the adjustive tractor for cervical dislocation.Methods Forty-seven patients were included between September 2007 and November 2011.There were 36 males and 11 females with age ranged from 7 to 62 (mean,35 years).The mean interval from injury to admission was 8.6 h (range,0.5-72 h).There were atlanto-occipital dislocation in 2 cases,C1.2 in 2 cases,C2.3 dislocation in 5 cases,C3.4 dislocation in 2,C4.5 in 9,C5.6 in 13,C6.7 in 14.Thirty cases were complicated by fracture.No facet locking occurred in sixteen cases.Facet locking was found in ten cases and bilateral facet locking was in 21 cases.After reduction,brace or internal fixation followed.According to American Spinal Injury Association (ASIA) spinal function impairment scale standard,there were 4 cases in level A,10 cases in level B,18 in C,10 in D,and 5 in E.According to Japanese Orthopaedic Association (JOA) spinal function rating standard,the mean JOA score was 9 (range,2-14).Results All 47 cases were reduced successfully without neuronal function aggravation.Traction power ranged from 7 to 60 kg (mean,25.6 kg),the mean time of traction was 8 min (range,3-10 min).The mean follow-up was 38 (range,6-48) months.All the patients achieved normal alignment and intervertebral height.The intervertebral body fusion was observed in all of cases,the mean fusion time was 3.3 months (range,3-6 months).One patient who experienced nonunion of vertebral arch fracture didn't receive further treatment because of absence of symptoms.At last follow-up,there were 3 cases in level A,1 in level B,4 in C,8 in D,and 31 in E according to ASIA scale.The mean JOA score was 12 (range,2-17).Conclusion The adjustive tractor is simple and safe for prompt reduction.

To determine the inhibition of IL-13 by recombinant sIL-13Rα2 in NIH-3T3 fibroblast cells for its potential therapeutic value in hepatic fibrosis caused by Schistosoma japanicum in mice . IL-13 and sIL-13Rα2 from liver of BALB/c mice infected with S.japonicum at different infection time (weeks 0,6,8,10 and 12) were analyzed by ELISA and RT-PCR. The recombinant sIL-13Rα2 expression plasmidwas constructed, followed by transfection into NIH-3T3 fibroblast cells. TypeⅠcollagen produced by NIH-3T3 cells were examined by RT-PCR and Western blotting. It was demonstrated that the expression of IL-13 increased gradually after infection, reached peak density (16.1586 pg/mL)at week 8 and then reduced but was still higher than the level of control mice(3.4146 pg/mL;P =0.017 ). The secretion of sIL-13R α2 reached to its peak 10 weeks after infection(4827.426 pg/mL)and then reduced slowly but still higher than normal(4057.112 pg/mL; P=0.021). Meanwhile, the changes in mRNA level of IL-13 and sIL-13R α2 were coincided with that examined by ELISA. Both IL-13 and sIL-13Rα2 reached their peak density (P=0.033) at week 8 and 10 (P=0.025) respectively, and they were followed by a slower degree of decrease. The sIL-13Rα2 could significantly inhibit the effect of IL-13 on NIH-3T3 fibroblast cells, showing decreased mRNA level(P =0.012)and protein level of typeⅠcollagen compared with normal groups(P =0.031). It is concluded that the sIL-13Rα2 can inhibit the effect of IL-13 on NIH-3T3 fibroblast cells which leads to a reduced production of typeⅠcollagen, demonstrating its potential therapeutic value in hepatic fibrosis of schistosomiasis.

[Objective]To investigate the method and efficiency of operative femoral supracondylar varus osteotomy combined with new blade plate on treatment of valgus deformity of knees.[Method]Thirty-seven patients with 43 knees with valgus deformity were treated with femoral supercondylar varus osteotomy with Giebel blade plate(Link company/Germany)from Oct.2000 to Oct.2005.The study group consisted of seven men with 8 knees and thirty women with 35 knees,the average age of the patients was 31.2 years(range,fifteen to seventy years).Eleven patients with 13 knees had lateralcompartment osteoarthritis,Ahlback stage Ⅰ eight patients with 10 knees and stage Ⅱ three patients 3 knees.The full-length Ap view of the lower extremity and the weightbearing AP view of the knee were obtained before and after operation,as well as the femoral angle and femoral-tibial angle were evaluated.The Giebel blade plates were taken out average 1.5 year after operation and the patients were followed-up,bone union and the change of the correction angles and the pain of the knees were evaluated.[Result]All deformity of the knees were well corrected,the femoral angle were corrected from 71.7?(62?～75?) to 82.1?(78?～85?),the average correction angle was 10.4?(8?～21?).With average 1.5 year follow-up thirty four patients with 40 knees got good bone union,two knees had non-union and we changed the internal fixationwith bone autc-grafting and got good results,as well as lost follow-up for one knee.The pain relieved in 10 knees with lateral osteoarthritis and disappeared in 3 knees after operation.[Conclusion]Femoral supracondylar varus deformity of the knee,the technique is simple and damage is slight,fixation is safety and effective.

[Objective]To measure the change of anatomic configuration of proximal tibial after high tibial osteotomy and probe its clinical consequences.[Method]From 2001 to 2005,there were 59 knees of 35 patients with medial unicompartmental osteoarthritis treated with closing-wedge high tibial osteotomy.Anatomic configuration of proximal tibia were measured both pre and postoperatively on radiographs.They included posterior slope angle of proximal tibia,tibial angle,lateral shift of articular surface of proximal tibial and level of the joint line.The alteration of the above features was calculated and analyzed statistically with paired t test.[Result]The mean tibial posterior slope angle were(8.9??2.6?)preoperatively and(5.0??2.3?)postoperatively.The tibial posterior slope angle was averagely decreased about(3.9??1.7?).Tibial angle were(99.1??4.3?)and(91.1??3.8?)before and after high tibial osteotomy respectively.Lateral shift of articular surface of proximal tibial were(46.2?3.6)% and(53.1?3.9)% in pre and postopratively.Level of joint line was(41.2?3.6)mm and(38.0?3.2)mm in pre and postopratively.Statistical analysis indicated that there was significant difference of posterior slope angle or tibial angle or lateral shift of articular surface of proximal tibial or level of joint line between pre and post operative(P

[Objective]To investigate the method and effeciency of management massive acetabular bone defect with impaction bone grafting plus mesh in revision total hip arthroplasty[Method]Twenty-one patients 21 hips with massive acetabular bone defect were treated with impaction bone grafting plus mesh during Dec 2001 to Jan 2006,including 6 men and 15 women,the average age were 51.9 years at the revision operation(range,38~77 years).The acetabular defects of the patients in this study group were type III(combined defect)according to the American Academy of Orthopaedic Surgeons(AAOS)classification scheme.At first the combined defect was transformed into cavitary defect with metal mesh,then the contained acetabulum was tightly packed with deep-frozen morselized cancellous allograft chips(size 7~10mm),the anatomy of the hip was reconstructed and the cup was inserted after pressurizing the cement directly onto the graft.The AP view of the hip at 3 days,3 months,1 year and yearly after the operation were obtained,cup migration according to the teardrop and radiolucent line were evaluated,at the same time the Harris hip score were also evaluated.[Result]The mean follow-up time was 2.8 years,the mean Harris hip score improved from 46.4 points preoperatively to 81.3 points at the final evaluation,no cup migration were found,except for one dislocation and one sciatic nerve injury,as well as lost follow-up for one hip.[Conclusion]Impaction bone grafting plus mesh is an effective approach to treat massive acetabular bone defect in revision total hip arthroplasty,it can restore bone stock and help the cup to be placed to the anatomic position,as well as provide execellent prothesis stability.