Objective:To compare the efficacy between locking plate internal fixation combined with iliac bone graft and separate locking plate internal fixation in the treatment of comminuted proximal humeral fracture in the elderly.Methods:A retrospective cohort study was conducted to analyze the clinical data of 42 elderly patients with comminuted proximal humeral fracture admitted to Affiliated Hospital of Qingdao University from January 2018 to January 2020. There were 20 males and 22 females, aged 65-75 years [(69.5±8.5)years]. According to Neer classification, there were 26 patients with three-part fracture and 16 with four-part fracture. Eighteen patients were treated by locking plate internal fixation combined with autologous iliac bone grafting (bone grafting group), and 24 patients were treated by locking plate internal fixation alone (non-bone grafting group). The operation time, intraoperative blood loss, postoperative drainage volume, hospitalization time, and fracture healing time were documented. Shoulder joint range of motion (forward flexion, extension, internal rotation and external rotation) and degree of humeral head height loss were measured at 1, 6, 12 months after operation and at the last follow-up. The Neer score and visual analogue score (VAS) of shoulder joint were evaluated at 12 months after operation and at the last follow-up. The complications were observed.Results:All patients were followed up for 12-24 months [(18.5±3.8)months]. There were no significant differences in operation time, intraoperative blood loss, postoperative drainage volume and hospitalization time between the two groups (all P>0.05). The fracture healing time in bone grafting group was (3.1±0.7)months, shorter than (4.2±0.9)months in non-bone grafting group ( P<0.05). In the two groups, the postoperative shoulder joint range of motion and degree of humeral head height loss increased significantly over time (all P<0.05). At 1, 6, 12 months after operation and at the last follow-up, the shoulder forward flexion range of motion in bone grafting group was (136.2±7.4)°, (139.3±6.9)°, (146.6±6.1)° and (148.4±4.7)°, higher than that in non-bone grafting group [(134.5±6.7)°, (136.5±7.0)°, (137.9±9.2)° and (138.3±7.9)°]; the shoulder extension range of motion in bone grafting group was (37.1±6.3)°, (40.5±4.4)°, (43.1±3.1) ° and (46.6±4.2)°, higher than that in non-bone grafting group [(35.5±4.6)°, (37.9±5.1)°, (41.3±2.5)° and (43.9±3.1)°]; the shoulder internal rotation range of motion in bone grafting group was (50.5±3.2)°, (54.1±5.6)°, (56.6±4.2)° and (58.9±3.6)°, higher than that in non-bone grafting group [(46.9±5.1)°, (50.3±4.2)°, (53.5±2.7)° and (55.4±5.1)°]; the shoulder external rotation range of motion in bone grafting group was (52.2±3.6)°, (55.6±4.3)°, (58.7±4.4)° and (60.2±5.6)°, higher than that in non-bone grafting group [(50.1±4.7)°, (52.6±5.7)°, (55.3±3.2)° and (57.3±4.1)°] ( P<0.05 or 0.01). At 1, 6, 12 months after operation and at the last follow-up, the degree of humeral head height loss in bone grafting group was (0.8±0.1)mm, (1.1±0.2)mm, (1.4±0.3)mm and (1.6±0.3)mm, smaller than that in non-bone grafting group [(1.1±0.2)mm, (1.4±0.3)mm, (1.7±0.6)mm and (2.0±0.5)mm] ( P<0.05 or 0.01). In the two groups, the postoperative shoulder joint range of motion and degree of humeral head height loss increased significantly over time (all P<0.05). There was no significant difference in Neer score of shoulder joint between the two groups before operation ( P<0.05). At 1, 6, 12 months after operation and at the last follow-up, the Neer score of shoulder joint in bone grafting group was (80.2±5.4)points, (82.1±5.0)points, (85.4±5.8) points and (90.3±4.6)points, higher than that in non-bone grafting group [(75.6±5.1)points, (80.4±5.5)points, (83.5±2.2)points and (87.4±4.8)points] ( P<0.05 or 0.01). There was no significant difference in VAS between the two groups before operation, at 1, 6, 12 months after operation or at the last follow-up (all P>0.05). The complication rate was 11.1% (2/18) in bone grafting group and was 20.8% (5/24) in non-bone grafting group ( P<0.05). Conclusions:For comminuted proximal humeral fractures in the elderly, locking plate internal fixation combined with autogenous iliac bone grafting can accelerate fracture healing, improve shoulder joint range of motion, promote functional recovery, and reduce complications in comparison with locking plate internal fixation alone.

Objective To study the effects of morroniside on the expression of Wnt signaling-related transcription factors neurogenin 2 (Ngn2), Pax6 and Tbr2 in the ischemic ipsilateral cortex 7 days after cerebral ischemia-reperfusion in rats. Methods 15 male Sprague-Dawley rats were randomly divided into sham group (n=3), ischemia group (n=3), and morroniside groups (low, medium and high dosage groups, n=3). The middle cerebral artery were occluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg 3 hours after operation. The expression of Ngn2, Pax6 and Tbr2 in the ischemic ipsilateral cortex were detected with Western blotting analysis 7 days after operation. Results The expression of Ngn2 increased in the ischemia group compared with the sham group (P<0.05), and it further increased the morroniside groups of medium and high dosage compared with the ischemia group (P<0.01). There was no significant difference between the ischemia group and sham group in the expression of Pax6, while it increased the morroniside groups of medium and high dosage compared with the ischemia group (P<0.01). There was no significant difference among all the groups in the expression of Tbr2. Conclusion Morroniside could increase the expression of Ngn2 and Pax6 in the ischemic ipsilateral cortex 7 days after ischemia-reperfusion in rats, suggesting promoting the neurogenesis after ischemia.

Objective To study the effects of morroniside on the expression of matrix metalloproteinase (MMP) -2 and MMP-9 in the peri- infarct cortex 3 days after cerebral ischemia- reperfusion. Methods 15 male Sprague-Dawley rats were randomly divided into sham group (n=3), ischemia group (n=3), and morroniside groups (low, medium and high dosage groups, n=3). The middle cerebral artery were occluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg 3 hours after operation. The expression of MMP-2 and MMP-9 in peri-infarct cortex were detected with immunohistochemistry staining 3 days after operation. Results The expression of MMP-2 and MMP-9 increased in the ischemia group compared with the sham group (P<0.01), and it decreased in all the morroniside groups compared with the ischemia group (P<0.01). Conclusion Morroniside could decrease the expression of MMP-2 and MMP-9 in the peri-infarct cortex 3 days after ischemia, suggesting protecting the function of blood-brain barrier from ischemia.

Objective To explore the effects of morroniside on the expression of Angiopoietin-1 (Ang-1) and Tie-2 in a rat after focal cerebral ischemia-reperfusion. Methods 20 male Sprague-Dawley rats were randomly divided into sham group (n=4), ischemia group (n=4), and morroniside groups (low, medium and high dosage groups, n=4). The middle cerebral artery were occluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg after operation. The expression of Ang-1 and Tie-2 in the ischemic ipsilateral cortex were detected with Western blotting analysis 7 days after operation. Results The expression of Ang-1 and Tie-2 increased in the ischemia group compared with the sham group (P<0.01), and both of them further increased in the morroniside groups of high dosage compared with the ischemia group (P<0.01), and the expression of Tie-2 also increased in the morroniside groups of medium dosage (P<0.001). Conclusion Morroniside could increase the expression of Ang-1 and Tie-2 in the ischemic ipsilateral cortex after ischemia-reperfusion in rats, suggesting promoting the angiogenesis after ischemia.

Objective To observe the expression of phosphorylated EphrinB2 in brain after focal cerebral ischemia/reperfusion in rats.Methods 24 male Sprague-Dawley rats were randomly divided into sham group (n=12) and model group (n=12). The model group was modeled as middle cerebral artery occlusion and reperfusion with nylon monofilament suture, and then was assessed with Longa's score. The expression of phosphorylated EphrinB2 in cerebral cortex was detected with immunohistochemistry and Western blotting. Results The expression of phosphorylated EphrinB2 and the number of positive cells were significantly higher in the sham group than in the control group (P<0.05). It existed in the vascular endothelium in cerebral cortex. Conclusion EphrinB2 signaling pathway is activated in ischemic stroke.

Objective To investigate the effect of morroniside on hematocrit percentage in a rat model of focal cerebral ischemia/reperfusion.Methods After the modified model induced with occlusion of middle cerebral artery (MCAO) with suture embolus, morroniside was administered intragastrically at the dose of 30 mg/kg (n=8), 90 mg/kg (n=8), and 270 mg/kg (n=8) once a day for 7 d. Acetyl salicylic acid (ASA) was used as positive drug (n=8). Hematocrit percentage was measured with automatic blood tester. Results Compared with the sham group, hematocrit percentage of the model group significantly increased (P<0.001), but increased less in those treated with morroniside and ASA (P<0.05). Conclusion Morroniside could inhibit the increase of hematocrit percentage in MCAO rats.

Parkinson's disease is a common progressive neurodegenerative disorder among old people. Parkinson's disease model induced with 6-hydroxydopamine has been used to research pathology and medication of Parkinson's disease.

Objective To explore the effects of morroniside on platelet aggregation induced by adenosine diphosphate (ADP) in focal cerebral ischemia/reperfusion in rats. Methods 48 Sprague-Dawley rats were randomly divided into sham group, model group, morroniside dose groups (30 mg/kg, 90 mg/kg, 270 mg/kg) and acetyl salicilic acid (ASA) group (10 mg/kg). The model of middle cerebral artery occlusion (MCAO) was established in all rats except the sham group. Born's turbidimetry was used to measure platelet aggregation rate in rats of MCAO model (in vivo). Results Compared with the model group, the platelet aggregation decreased significantly in the morroniside high dose group (P<0.001). Conclusion Morroniside has the effect of anti-platelet aggregation in focal cerebral ischemia/reperfusion in rats.

Objective To explore the effect of morroniside on blood viscosity in focal cerebral ischemia/reperfusion in rats. Methods The animal model was induced with occlusion of middle cerebral artery (MCAO), and morroniside (30 mg/kg, 90 mg/kg, 270 mg/kg) was then administered intragastrically for 7 d. Whole blood viscosity and plasma viscosity were detected with auto-hemorheological instrument and microplasma testing device. Results Compared with sham-operated group, both whole blood viscosity and plasma viscosity significantly increased in ischemic rats (P<0.001); however, morroniside reduced whole blood and plasma viscosity noticeably (P<0.001). Conclusion Morroniside can inhibit the increase of blood viscosity induced by focal cerebral ischemia/reperfusion in rats.

The pathways of brain injury caused by ischemic stroke are complicated. Due to those largely ineffective current therapeutic strategies, the development of new and efficient therapeutic interventions is clearly needed. This article summarized the progress in the pathogenesis of ischemic stroke, the drugs for treatment and the therapeutic time window.