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 explore the safety of transanal re-excision (TAR) after positive-margin local resection for early rectal cancer.Methods:A retrospective analysis was made data of 44 patients with rectal cancer after local excision from Mar 2006 to Oct 2018 at the Department of Colorectal Surgery, Cancer Hospital of Chinese Academy of Medical Sciences. All patients had positive margin or suspicious tumor remains after local excision, and subsequently salvage TAR surgery was performed after informed consent was given.Results:Forty-four patients after local excision were with pathologically showed residual condition, including 26 cases of positive margin and 18 cases of suspicious tumor remaining. The pathological types were all adenocarcinoma. Forty-one (93%) patients with pT1 and 3 (7%) patients with pT2. The median follow-up time after salvage TAR was 100 (11-164) months. During follow-up, 3 patients (7%) developed mild anal incontinence. One patient (2%) had local recurrence, 3 (7%) patients had distant metastases, and 3 patients (7%) died of non-tumor specific deaths. The overall 5-year survival rate and disease-free survival rate were 98% and 93 %, respectively.Conclusions:Transannal full thickness tumor re-excision is safe and reliable for the salvage treatment after non-complete local resection of early rectal cancer. The long-term follow-up results show that the 5-year survival rate is comparable to that of radical surgical resection, and with a good anal function.

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.

BACKGROUND:Vertebral compression fractures are the most common vertebral fractures in the elderly patients with osteoporosis, and the correlation between the compression of anterior border of vertebral body and adjacent vertebral refractures is not clear.
OBJECTIVE:To establish a model of different compression of T12vertebral body with finite element method, and analyze the relationship between the compression of T12vertebral body and the stress of adjacent vertebral plate.
METHODS:Based on thoracolumbar CT data of normal adult volunteers, MIMICS/3-matic was imported. Through image segmentation, repair and three-dimensional mesh of accessto thoracic and lumbar T11-L1data, grid assigned material properties was imported to ABAQUS so as to establish ligament, joint and other small features and obtain realistic three-dimensional finite element model. The six degrees of freedom, including anteflexion, posterior extension, left and right flexion, left and right rotation, were loaded, to verify the validity of the normal model. With the frontier of vertebral body compression to 90%, 80%, 70%…10% of the nine states, MISES stressesof the T11andL1segment intervertebral disc endplate were extracted; the relationship curve of compression state and endplate stress was obtained.
RESULTS AND CONCLUSION:(1) The model was highly realistic and could reflect the actual stress state. (2) The stress value of T11vertebral body and L1vertebral body was positively correlated with the compression of T12vertebral body. Increased stress may lead to an increased likelihood of end plate fractures, which increases the risk of fractures in the adjacent vertebralbodies.

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.

BACKGROUND:The surgical treatment of thoracolumbar burst fracture combined with spinal cord injury is to relieve mechanical compression on the spinal cord and reconstruct spinal stability through internal fixation.This theory is derived from a lot of animal experiments and important biomechanical principles,but the available clinical data are stil scarce.OBJECTIVE:To investigate the efficacy of posterior decompression and screw internal fixation for the treatment of thoracolumbar fractures combined spinal cord compression,and to evaluate vertebral body height,kyphosis angle and neurological function.METHODS:A retrospective study was performed among 75 patients with thoracolumbar fractures combined spinal cord compression,who were recruited from Department of Orthopedics,the First People's Hospital of Shunde District of Foshan City,from January 2010 to February 2013.They underwent posterior decompression and internal fixation.The preoperative and postoperative kyphosis angle,vertebral height and neurological function were compared.RESULTS AND CONCLUSION:The preoperative kyphotic angle was (25.2±2.1)° and postoperative kyphotic angle was (8.8±2.3)°,with significant differences (P ＜0.05).Preoperative vertebral body height was (58.4±14.2)％and postoperative vertebral body height was (92.3±6.8)％.According to ASIA score,48 cases had slight impairment of neurological function,scores more than 40 points,and 45 of them had completely recovered walking ability,the recovery rate was 94％; the remaining 27 cases had moderate or severe neurological function impairment,scoring less than 40 points,and 15 of them appeared obvious recovery of neurological function,therecovery rate was 56％.Posterior decompression and internal fixation for treatment of thoracolumbar burst fracture combined with spinal cord injury can effectively restore the vertebral height and kyphosis,and improve significantly neurological function.

Objective To evaluate the role of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) in the spinal cord in the maintenance of diabetic neuropathic pain in rats.Methods Pathogenfree male Sprague-Dawley rats,aged 2 months,weighing 180-220 g,were used in the study.Diabetes mellitus was induced by intraperitoneal streptozotocin (STZ) 60mg/kg and confirmed by blood glucose ＞ 16.7 mmol/L at 72 h after STZ injection.Twenty diabetic rats were randomly allocated to diabetic neuropathic pain group (DN group,n =10) and apocynin (specific NADPH oxidase inhibitor) group (A group,n =10).Another 10 agematched normal rats served as control group (C group,n =10).Twenty-eight days after STZ injection,apyconin 5 mg/kg was injected intraperitoneally once a day for 7 consecutive days in A group.Paw withdrawal threshold to yon Frey filament stimulation (PWT) was measured before STZ injection (T1) and at 7,14,21,28 and 35 days after STZ injection (T2-6).The rats were sacrificed after PWT was measured at T6 and L4.5 segments of the spinal cord were removed for determination of NADPH oxidase subunits gp91phox and p47phox expression,MAD content and SOD activity.Results Compared with C group,PWT was significantly decreased at T3-5,gp91phox and p47phox expression was up-regulated,MAD content was increased,and SOD activity was decreased in DN and A groups.Compared with DN group,PWT was significantly increased at T6,gp91phox and p47phox expression was downregulated,MAD content was decreased,and SOD activity was increased in A group.Conclusion NADPH oxidase in the spinal cord is involved in the maintenance of diabetic neuropathic pain in rats.

Objective To establish mice models of Kawasaki disease by Lcatobacillus casei cell wall extract(LCWE) ,in order to provide experimental materials for follow-up study .Methods LCWE group was given LCWE 0 .1 mL per mouse(containing 200 mg LCWE) via abdominal intramuscular injection .PBS group was given 0 .1 mL PBS per mouse .Orbital blood samples were collected respectively at the 1st ,3rd and 28th day after administration .The heart ,lung ,liver ,kidney ,spleen and other organs tissue samples were collected for pathological section ,HE staining .The histopathological changes were investigated ,and the routine blood test was proceeded .Results The WBC of LCWE group showed a trend of rising at the 1st ,3rd and 28th day after administration .PLT and MPV of LCWE group increased at the 3rd day after administration ,which returned to normal levels at the 28th day after adminis-tration .The pathological section showed the blood vessel walls of heart tissue enlargement ,surrounded and infiltrated by inflamma-tory cells infiltration ,the atheromatous plaque in blood vessels occasionally .Conclusion The study established mice model of Ka-wasaki disease successfully .

BACKGROUND: Vertebrae axial rotation is a basic deformity of scoliosis, the rotational degree of which is hard to measure due to the field limitation of posterior spinal instrumentation. Currently, vertebrae rotational degree is measured according to preoperative X-ray film or CT, while no reports concerning measuring vertebrae rotational degree during operation. OBJECTIVE: To explore the feasibility of measurement of vertebrae rotational degree with the entry point of pedicle screws.METHODS: Design of the path of pedicle screws on CT scans before surgery, a line bisection and perpendicular to another connecting bilateral entry point of pedicle screws, and the angle of vertebral rotation (EPPsag) was taken as the angle between this line and the saggital plane. The difference among vertebrae rotational degrees measured by conimeter, Ho's method and EPPsag was compared by Wilcoxon signed rank test. The intra-observer and inter-observer difference was analyzed with One-WayANOVA. Conimeter was used to measure vertebrae rotational degree of each vertebra in 9 lumbar specimens, and the results was compared to EPPsag.RESULTS AND CONCLUSION: There was no significant difference among EPPsag, actual rotational degree and measuring results of Ho's method (P>0.05). The One-Way ANOVA showed that the differences between intra-observer analysis and inter-observer analysis (P>0.05). The results demonstrated that EPPsag can exhibit vertebrae rotational degree accurately and repeatability. This anger can be obtained accurately with the instrument if the vertebrae rotational degree not exceeding 30°.

0.05). However,the accuracy in placement pedicle screws and derotation rate of apical vertebrae were much higher in the individually treated group than those in the standard group (P=0.001,0.02).[Conclusion]The accuracy in placement pedicle screws and correction effects on transverse plane of patients with Lenke Ⅰ AIS can be improved significantly by individual selection of entrance point.