A missense mutation in lectin domain of thrombomodulin causing functional deficiency.

Thrombomodulin (TM) functions in coagulation, fibrinolysis and inflammation by its cofactor activity for protein C, thrombin-activatable fibrinolysis inhibitor (TAFI) activation and high mobility group box 1 (HMGB1) degradation induced by thrombin. It has been widely reported that mutations in TM are related to thromboembolic diseases but hardly in lectin domain. Here we report our findings about the functional deficiencies in TM caused by substitution of aspartate with tyrosine at residue 126. Three patients suffering from recurrent thromboembolic diseases were identified with this mutation and their plasma soluble TM levels were decreased. Transfected cells expressing wild-type TM or the variant and corresponding proteins were used to examine TM functions in vitro. The cofactor activity of the mutant for protein C, TAFI activation was reduced to approximately 50% and 60% respectively. Loss in anti-inflammation due to weakened HMGB1 degradation was also observed. And the study with thrombosis models of mice suggested the decreased inhibition of thrombus development of the mutant. Together the results showed deleterious changes on TM function caused by this mutation, which may explain the thrombophilia tendency of the patients. This work provided supportive evidence that mutation in lectin domain of TM might be related to thrombotic diseases and may help us better understand the physiological roles of TM.

Study on the effect of different frequencysling exercise therapyon stroke patients / 中国综合临床

Objective:To investigate the effects of different frequency sling exercise therapy (SET) on the balance of trunk control and walking ability in stroke patients.Methods:A total of 90 patients with stroke who were admitted to the Department of Rehabilitation Medicine, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, from January 2018 to December 2018, received sling exercise therapy on a routine basis and were divided into 1 time/Day low frequency group, 2 time/Day medium frequency group, 3 time/Day high frequency group, 20 min/time, for a total of 3 months.After 1, 2 and 3 months, trunk control test (TCT), Berg balance scale(BBS), functional ambulation classification (FAC) and modified Barthel Index (MBI) were used to evaluate the three groups of patients.Results:There were significant differences in TCT, BBS, FAC and MBI between the low, middle and high frequency groups (all P < 0.05). The scores of TCT in the low, middle and high frequency groups were (36.21±6.31), (42.51±4.33), (49.52±4.90) and (41.23±6.31), (50.32±8.32), (58.12±7.23) respectively, and the scores of BBS were (15.11±4.31), (19.69±5.86), (24.56±8.74) and (21.43±5.37), (27.61 ± 7.50), (33.81±6.99) respectively, compared with those before treatment )The scores of (24.69±9.33), (22.84 ± 10.11) and (9.32 ± 3.11), (9.504.10), (9.47 ± 3.73) were significantly improved, and the differences between the high frequency group and the low frequency group and the medium frequency group were statistically significant (all P< 0.05), but there was no statistically significant difference between the three groups after three months of training ( P> 0.05). There was no significant difference between fAC and MBI in the low, medium and high frequency group, but there was no significant difference between the two groups after training for 2 and 3 months There were significant differences between fAC ((1.84±0.41), (2.39±0.44), (3.29 ± 0.33) and MBI ((27.32 ± 9.33), (34.45 ± 9.21), (44.77 ± 10.27) and (41.33±11.21), (52.73±12.31), (75.94±13.22)). There was significant difference between the high frequency group and the low frequency group ( P< 0.05). Conclusion:Multiple sling exercise therapy in one day can further improve the balance of trunk control and walking ability of stroke patients, and shorten the course of disease.