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 evaluate the long-term impact of three different outdoor activity intervention strategies on the prevalence of myopia among school-aged children in China.Methods:Cross-sectional data from the Refractive Error Study in Children (RESC) on the baseline prevalence of myopia and 10-year longitudinal data from the Guangzhou Twin Eye Study (GTES) on the baseline incidence of myopia were utilized.The effect size of outdoor activity intervention was derived from longitudinal data of the Guangzhou Outdoor Activity Longitudinal Study (GOALS). Three intervention strategies were proposed: intervention for children in grades 1 to 6 (Strategy A), intervention for children in grades 1 to 3 (Strategy B), and intervention for children from the last year of kindergarten to grade 3 (Strategy C). Outdoor activity interventions across all strategies included an extra 40 minutes of daily outdoor activity time.Simulated analyses assumed that the prevalence of myopia would decrease with declining incidence and increasing school grade, and the degree of myopia among highly myopic children would decrease with delayed myopia onset.This study was approved by the Ethics Committee of Zhongshan Ophthalmic Center (No.2006-5).Results:With prolonged intervention time, the overall prevalence of myopia in children showed a significant declining trend.After 5 years of implementation, Strategy A resulted in a decrease in myopia prevalence from 34.67% to 25.71%, which decreased to 24.89% after 10 years, with an average annual reduction of 0.98%.Strategies B and C had similar long-term effects, with myopia prevalence after 10 years being 26.00% and 26.20% respectively, with an average annual reductions of 0.87% and 0.85%.Strategy A yielded the greatest reduction in myopia severity, with a decrease of -5.94 D after 5 years and -5.88 D after 10 years in the initial 15-year-old highly myopic individuals.Strategy B followed with -6.08 D and -6.02 D after 5 and 10 years, respectively.Conclusions:Implementing intensified outdoor activity intervention among children in grades 1 to 6 may be the recommended strategy to reduce the overall prevalence of myopia in regions with high rates of myopia among school-aged children.

China has recently proposed a countrywide myopia control strategy for children and adolescents due to the rapidly increasing incidence and early onset of myopia.Recent studies have proposed interventions and methods for myopia prevention and control, such as low-dose atropine and orthokeratology lens, while the current strategies are subject to cause inconvenience and ineligible risks of side effects.Although accumulating evidence has shown that increased time outdoors is effective in reducing the risk of myopia development, its effect is closely related to light exposure.Interventions to enhance time spent outdoors or further increase on light exposure to prevent myopia are pragmatically challenging.A multicenter randomized controlled trial (RCT) led by Zhongshan Ophthalmic Center, adopted repeated low-level red-light (RLRL) to deliver light on the retina directly for a much shorter duration of exposure but repeatedly, and further assessed the efficacy and safety of RLRL therapy in myopia control among children.Findings from the RCT showed promising efficacy of RLRL therapy in slowing myopia progression among school-age children with mild to moderate myopia, providing high-level evidence for RLRL therapy as a safe and efficacious strategy for reducing myopia progression.This paper summarized the findings from the RCT, discussed how to adopt such a treatment for myopia control in clinical practice, and further suggested eye care service providers to follow the research progress of RLRL therapy for myopia prevention and control.

Objective To observe the multimodal imaging characteristics of multiple evanescent white dot syndrom (MEWDS).Methods This was a retrospective series case study.Eighteen patients (18 eyes) diagnosed with MEWDS in Eye Center of The Second People's Hospital of Foshan from September 2015 to April 2017 were enrolled in this study.There were 12 females and 6 males,with the mean age of 35.9 years.The disease course ranged from 3 to 90 days,with the mean of 14 days.All the patients underwent BCVA,slit-lamp microscope with +90D preset lens,fundus photography,spectral domain OCT (SD-OCT) and FAF examinations.FFA was simultaneously performed in 6 eyes,FFA and ICGA were simultaneously performed in 12 eyes.Ten patients received the treatment of glucocorticoids and vasodilator substance,and other 8 patients without any treatment.The follow-up duration was 4.5 months.The multimodal imaging characteristics were reviewed and analyzed.Results Fundus color photography showed a variable number of small dots and large spots lesions (14 eyes),and/or fovea granularity (7 eyes) and disk swelling (5 eyes).A variable number of little dots and larger spots lesions showed respectively in FFA,FAF and ICGA were needle-like dots distributed in a wreathlike pattern and a large plaque occasionally confluent of early highly fluorescent,highly autofluorescence and hypofluoresence.Combined hypofluorescent spots with overlying dots were observed in 10 eyes of the late stages of the ICGA.Black lesions in the gray background show in ICGA were the most obvious and the most extensive,gray-white lesions in the gray-black show in FAF were the second,light gray-black lesions in the gray show in FFA were the least.Gray-white lesions in an orange background show in fundus photography were not obvious and transient.SD-OCT showed disruption of the ellipsoid zone and/or accumulations of hyperreflective material from the ellipsoid layer toward the outer plexiform layer and vitreous cells.During the period of following-up,some patients were prescribed low-dose glucocorticoid and some not,almost all the patients except one patient experienced recovery in BCVA and the lesions in fundus imaging.Conclusions The lesions in MEWDS eyes in modern multimodal imaging modalities among fundus photography (fovea granularity),FFA (needle-like dots distributed in a wreathlike pattern and a large plaque occasionally confluent of early highly fluorescent),ICGA (flake hypofluorescent) and SD-OCT (disruption of the ellipsoid zone) showed good consistency.Almost eyes were recovery.

Objective To compare volar plating and nonoperative treatment for senile comminuted fractures of the distal radius. Methods From October 2012 to June 2015, 46 senile comminuted fractures of the distal radius ( AO types B and C ) were treated surgically or conservatively. Twenty old patients were managed by open reduction and fixation with a volar locked plate. They were 7 men and 13 women, with an average age of 67. 9 ± 10. 7 years, including 7 cases of AO type 23-B and 13 cases of AO type 23-C. Twenty-six patients were managed with closed reduction and plaster cast. They were 8 men and 18 women, with an average age of 66. 2 ± 11. 5 years, including 10 cases of AO type 23-B and 16 cases of AO type 23-C. The 2 groups were compared in terms of follow-up time, union time and wrist functional scores and complica-tions. Results There was no significant difference between the 2 groups in follow-up time ( P > 0. 05 ) . Fractures in the 2 groups all united about 11 weeks after surgery. According to Dienst scoring for reduction, the volar plating group had 13 excellent cases, 4 good ones, 2 fair ones and one poor case, with an excellent to good rate of 85. 0％ while the nonoperative group had 5 excellent cases, 10 good ones, 5 fair ones and 6 poor ones, with an excellent to good rate of 57. 7％. A significant difference was shown between the 2 groups ( P <0. 05 ) . At final follow-ups, the volar plating group had significantly lower Gartland & Werley wrist functional score ( 2. 16 ± 1. 82 ) and complication rate ( 30. 0％, 6/20 ) than the nonoperative group [ 6. 62 ± 3. 78 and 53. 8％( 14/26 ) , respectively ] ( P <0. 05 ) . Conclusion In treatment of senile comminuted fractures of the distal radius, volar locked plating may lead to better functional recovery and fewer complications than nonoper-ative management. However, one should take full account of the physical condition and preference of the patient when surgery is chosen.

Objective To explore the clinical characteristics of pattern of phlegm heat and bowel excess in acute stage of stroke involving meridian-collateral or involving zang-fu organs from the aspects of severity of neurological impairment, pattern distribution at different time points and duration of bowel excess.Methods The basic information,scores of National Institute of Health Stroke Scale(NIHSS), whether bowel qi being unobstructed or not,duration of bowel excess,and pattern distribution at different time points(onset for 1 d to 3 d,onset for 4 d to 7 d and onset for 8 d to 14 d)were inputted based on structured data by using retrospective analysis of medical records in 204 cases of pattern of phlegm heat and bowel excess of stroke involving meridian-collateral(meridian-collateral group)and 217 cases of pattern of phlegm heat and bowel excess of stroke involving zang-fu organs(zang-fu organ group).The clinical characteristics from the data were compared, analyzed and studied.Results The severity of neurological impairment except of conscious state was significantly higher in zang-fu organ group than that in meridian-collateral group(P<0.01).The average duration of unobstructed bowel qi was significantly longer in zang-fu organ group than that in meridian-collateral group(P<0.01), and the percentage of patients with throughout obstructed bowel qi was significantly higher in zang -fu organ group than that in meridian-collateral group in acute stage of stroke.The pattern of phlegm heat and bowel excess showed a decline trend after stroke onset for 1 d to 14 d in meridian-collateral group, and showed an ascending trend after stroke onset for 1 d to 7 d and a decling trend after stroke onset for 8 d to 14 d in zang-fu organ group.The cases of pattern of qi deficiency with blood stasis or pattern of collaterals blocked by wind -phlegm and static blood were significantly higher in meridian-collateral group at 4-14 d than those at 1-3 d,and cases of pattern of wind stirring due to yin deficiency,pattern of phlegm heat and blood stasis or pattern of wind phlegm and blood stasis were significantly higher in zang-fu organ group at 8 -14 d than those at time point 1.Conclusion The duration of pattern of phlegm heat and bowel excess is posi-tively correlated to the severity of stroke,that is,neurological impairment is more serious and duration is longer in patients with pattern of phlegm heat and bowel excess of stroke involving zang -fu organs.

Objective To observe the effect of tendon-bone healing after anterior cruciate ligament reconstruction through BFGF and PDGF.Methods Based of seventy two healthy matured New Zealand white rabbits underwent ACL reconstruction.Devide three groups through different methods,group BFGF,group PDGF,group normal.Results The maximum loads of group BFGF and PDGF after 2 and 5 weeks are higher than group normal,there was significant difference in maximum loads (P <0.05).The max stiffness of group BFGF and PDGF after 2 and 5 weeks are higher than group normal,there was significant difference in maximum loads(P <0.05).Conclusion The group BFGF and PDGF can promote tendon-bone healing by increasing the vascularization and blood vessels of the tendon-bone interface and vascular endothelial growth factor.In biomechanics,group BFGF and PDGF can pro-mote maximum loads、max stiffness and hardness of tendon-bone healing.

[Objective] To study the relationship between structure of anterior segment tissues and open angle(AA) in normal subjects.[Methods] A total of 211 eyes from 211 normal subjects were enrolled,whose anterior chambers and lens were scanned using anterior segment optical coherence tomography (AS-OCT).The measuring items included AA,anterior chamber depth (ACD),anterior chamber horizontal diameter (ACHD),anatomical anterior chamber depth (AACD),ciliary band length (CBL),iris thickness (IT),lens thickness (LT),lens position (LP) and lens anterior apex position (LAAP).The relationship between the 8 biometric parameters and AA was analyzed using linear correlation,respectively.[Results] The mean of AA was (40 ± 17)°,with (44 ± 18)° in male,and (37 ± 16)° in female.The difference of AA between male and female was statistically significant (t ＝ 2.893,P ＝ 0.004).There was significant correlation between AA and ACD (r ＝ 0.721,P ＝ 0.000),LT (r ＝ -0.545,P ＝ 0.000),CBL (r ＝ 0.615,P ＝ 0.000),LAAP (r ＝ -0.717,P ＝ 0.000),LP (r ＝ 0.557,P ＝ 0.000),and ACHD (r ＝ 0.175,P ＝ 0.011).There was no significant correlation between AA and AACD (r ＝ 0.130,P ＝ 0.059),IT (r ＝ 0.129,P ＝ 0.061).[Conclusion] The AA of females was narrower than that of males.In normal subjects,the most important factors which determine AA are the lens,the location of the peripheral iris and ciliary body.

A sagittal plane model of knee joint based on crossed-four-bar-linkage-based tibiofemoral joint model has been developed using geometric and force equilibrium constraints. The model predicts and explains the movement of contact point on the patella and femur, variation of patellar and patellar tendon angle, variation of patellar mechanism angle and variation of patellofemoral contact force and patellar tendon force. The computed results agree well with the published experimental results.
Biomechanical Phenomena ; Humans ; Knee Joint ; anatomy & histology ; physiology ; Models, Biological ; Movement ; physiology ; Patella ; anatomy & histology ; physiology

The mechanical model of knee is a system of constructional elements with specific restrains and material properties, which are deduced from the components of knee based on their functions and junctions. Kinematics and kinetics of knee can be calculated from the mechanical model. A review of some mechanical models of knee are shown in this paper.
Biomechanical Phenomena ; Computer Simulation ; Humans ; Knee Joint ; physiology ; Models, Biological ; Range of Motion, Articular ; physiology ; Stress, Mechanical