摘要
Objective:To investigate the effects of Xiangshao granules on behavior and oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs) in the medial prefrontal cortex (mPFC) of post-stroke depression (PSD) mice.Methods:Eighty C57BL/6 mice were divided into sham-operated group, middle cerebral artery occlusion (MCAO) group, PSD+PBS group, and PSD+Xiangshao group ( n=20). PSD models were constructed using mild chronic unforeseeable stress (CUMS) and solitary feeding after MCAO. MCAO models were evaluated by laser speckle contrast imaging (LSCI), modified neurological severity score (mNSS) and TTC staining. PSD models were evaluated by body mass, sugar and water preference test and tail suspension test. After PSD modeling, mice in the sham-operated group, MCAO group, and PSD+PBS group were given 0.2 mL PBS, while mice in the PSD+Xiangshao group was given Xiangshao granules at dosage of 60 mg/kg (dissolved in 0.2 mL PBS); all were given via intragastric administration once a d for 28 d. Number of OPCs and OLs in mPFC was detected by immunofluorescence. Expressions of myelin basic protein (MBP) and phosphatidylinositol 3-kinase/serine/threonine kinase/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway proteins in mPFC were detected by Western blotting. Results:(1) Model verification results: LSCI showed obvious changes of cerebral blood flow in the middle cerebral artery supply area before, during and after MCAO; TTC staining showed typical red non-infarct area and white infarct area in MCAO group, PSD+PBS group and PSD+ Xiangshao group; mNSS scores in MCAO group, PSD+PBS group and PSD+ Xiangshao group were all >4, without significant differences ( P>0.05); the MCAO model was successfully constructed. After PSD and before treatment, the PSD+PBS group and PSD+Xiangshao group had significantly decreased body weight and sugar-water preference, and statistically prolonged tail suspension immobilization time compared with sham-operated group and MCAO group ( P<0.05); the PSD model was successfully constructed. (2) Results of mouse behavior experiment after treatment: significant differences in body weight, sugar-water preference and tail suspension time were noted in mice of the 4 groups 28 d after treatment ( P<0.05); PSD+Xiangshao group had significantly increased body weight and sugar-water preference and decreased tail suspension immobilization time compared with PSD+PBS group ( P<0.05). (3) Number of OPCs (Olig2 +PDGFRa +), proliferative OPCs (Ki-67 +PDGFRa +, EdU +PDGFRa +) and OLs (Olig2 +CC1 +), and relative MBP, p-PI3K, p-AKT and p-mTOR protein expressions in mPFC of the 4 groups were significantly different ( P<0.05); compared with those in PSD+PBS group, the above cell number and relative protein expressions in PSD+Xiangshao group were significantly increased ( P<0.05). Conclusion:Xiangshao granules can promote the OPCs proliferation and OLs maturation by activating PI3K/AKT/mTOR signaling pathway in mPFC, thus playing a role in PSD.
摘要
Chronic cerebral hypoperfusion leads to white matter injury (WMI), which subsequently causes neurodegeneration and even cognitive impairment. However, due to the lack of treatment specifically for WMI, novel recognized and effective therapeutic strategies are urgently needed. In this study, we found that honokiol and magnolol, two compounds derived from Magnolia officinalis, significantly facilitated the differentiation of primary oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes, with a more prominent effect of the former compound. Moreover, our results demonstrated that honokiol treatment improved myelin injury, induced mature oligodendrocyte protein expression, attenuated cognitive decline, promoted oligodendrocyte regeneration, and inhibited astrocytic activation in the bilateral carotid artery stenosis model. Mechanistically, honokiol increased the phosphorylation of serine/threonine kinase (Akt) and mammalian target of rapamycin (mTOR) by activating cannabinoid receptor 1 during OPC differentiation. Collectively, our study indicates that honokiol might serve as a potential treatment for WMI in chronic cerebral ischemia.
Subject(s)
Magnolia , White Matter , Brain Ischemia/metabolism , Oligodendroglia/metabolism摘要
Objective@#To compare the medium-term clinical and radiologic outcomes between anterior decompression with fusion (ADF) and posterior open-door laminoplasty (LAMP) in the treatment of multi-level cervical spondylotic myelopathy (MCSM).@*Methods@#Data of 121 patients meeting to inclusion criteria from October 2011 to February 2016 were retrospectively analyzed. All the patients were treated with ADF (ADF group, n=57) or LAMP (LAMP group, n=64) for MCSM. There were 39 males and 18 females in ADF group, aged from 35 to 77 years, with an average age of 58.8±10.1 years. And there were 64 cases in LAMP group, including 48 males and 16 females, aged from 28 to 82 years, with an average of 60.6±12.2 years. The operation time and blood loss were recorded. The clinical efficacy was evaluated by Japanese Orthopaedic Association Scores (JOA), improvement rate and visual analogue scale (VAS) before operation, 1, 3, 6, 12 and 24 months after operation and at the latest follow-up. At the same time, sagittal alignment of the C2-C7 lordotic angle and range of motion (ROM) in flexion and extension on plain X-rays was measured. Residual anterior compression to the spinal cord (ACS) in LAMP group on MRI was investigated. The incidence of complications such as axial symptoms and C5 nerve root paralysis were recorded.@*Results@#The average follow-up period was 25.6±3.8 months in ADF group and 27.3±4.1 months in LAMP group. Demographics were similar between the two groups. The mean JOA scores in ADF group increased from preoperative 8.25±2.33 to 14.62±3.15 at the latest follow-up, with an average recovery rate of 72.81%±11.32%. The mean JOA scores in LAMP group increased from preoperative 8.84±3.65 to 12.97±4.32 at the latest follow-up, with an average recovery rate of 66.54%±14.75%. The difference between two groups was statistically significant. Both of the VAS scores in the two groups decreased significantly at 1 month after the surgery, but the difference between the ADF group (1.92±0.75) and the LAMP group (2.78±0.68) was statistically significant (t=2.364, P=0.021). There was no significant difference in VAS score between the two groups at 3 months after operation. Cervical lordosis of ADF group increased from 15.3°±7.6° to 19.2°±5.7°, while that of LAMP group decreased from 16.8°±8.3° to 13.6°±4.3°. There was significant difference in cervical curvature between the two groups at the latest follow-up. Both two groups exhibited decreased cervical ROM, 15.2°±3.6° and 18.1°±4.1°, respectively, and the difference between two groups was statistically significant (t=3.392, P=0.000) . At the latest follow-up, the incidence of complication was 35.1% in ADF group and 20.3% in LAMP group, and the difference between two groups has no statistically significant. The LAMP group was divided into two subgroups: (1) ACS(+)(n=11) comprising patients who had ACS after surgery, and (2) ACS(-) (n=53) comprising patients without ACS. At the latest follow-up, the average JOA score of patients with anterior residual compression of spinal cord was 10.85±5.46, while the average JOA score of patients without anterior residual compression of spinal cord was 14.18±4.52. The recovery rate differed significantly between the ACS(+) and ACS(-) groups, 40.52%±9.76% and 70.38%±10.52%, respectively. Also at the latest follow-up, the cervical curvature, ROM and ROM loss angle were 10.2°±7.3°, 15.6°±6.7° and 11.8°±8.3° in the group with anterior residual compression of spinal cord, respectively. The groups without anterior residual compression of spinal cord were 15.8°±6.5°, 20.4°±10.2° and 8.8°±6.8°, respectively.@*Conclusion@#Both ADF and LAMP groups provided good outcomes at 2-year time-point whereas ADF could achieve more satisfactory outcomes and better sagittal alignment at the middle-term. ADF can remove the compression directly, maintain the curvature of cervical vertebra effectively and restore the nerve function well. The clinical outcomes after LAMP could be influenced by ACS, due to the reduction of cervical curvature and the decrease of cervical range of motion.
摘要
Objective To compare the medium?term clinical and radiologic outcomes between anterior decompression with fusion (ADF) and posterior open?door laminoplasty (LAMP) in the treatment of multi?level cervical spondylotic myelopathy (MCSM). Methods Data of 121 patients meeting to inclusion criteria from October 2011 to February 2016 were retrospectively analyzed. All the patients were treated with ADF (ADF group, n=57) or LAMP (LAMP group, n=64) for MCSM. There were 39 males and 18 females in ADF group, aged from 35 to 77 years, with an average age of 58.8±10.1 years. And there were 64 cases in LAMP group, including 48 males and 16 females, aged from 28 to 82 years, with an average of 60.6±12.2 years. The operation time and blood loss were recorded. The clinical efficacy was evaluated by Japanese Orthopaedic Association Scores (JOA), im?provement rate and visual analogue scale (VAS) before operation, 1, 3, 6, 12 and 24 months after operation and at the latest follow?up. At the same time, sagittal alignment of the C2-C7 lordotic angle and range of motion (ROM) in flexion and extension on plain X?rays was measured. Residual anterior compression to the spinal cord (ACS) in LAMP group on MRI was investigated. The inci? dence of complications such as axial symptoms and C5 nerve root paralysis were recorded. Results The average follow?up period was 25.6±3.8 months in ADF group and 27.3±4.1 months in LAMP group. Demographics were similar between the two groups. The mean JOA scores in ADF group increased from preoperative 8.25±2.33 to 14.62±3.15 at the latest follow?up, with an average re?covery rate of 72.81%±11.32%. The mean JOA scores in LAMP group increased from preoperative 8.84±3.65 to 12.97±4.32 at the latest follow?up, with an average recovery rate of 66.54%±14.75%. The difference between two groups was statistically significant. Both of the VAS scores in the two groups decreased significantly at 1 month after the surgery, but the difference between the ADF group (1.92±0.75) and the LAMP group (2.78±0.68) was statistically significant (t=2.364, P=0.021). There was no significant dif?ference in VAS score between the two groups at 3 months after operation. Cervical lordosis of ADF group increased from 15.3°± 7.6°to 19.2°±5.7°, while that of LAMP group decreased from 16.8°±8.3°to 13.6°±4.3°. There was significant difference in cervi?cal curvature between the two groups at the latest follow?up. Both two groups exhibited decreased cervical ROM, 15.2°±3.6°and 18.1°±4.1°, respectively, and the difference between two groups was statistically significant(t=3.392, P=0.000). At the latest fol?low?up, the incidence of complication was 35.1% in ADF group and 20.3% in LAMP group, and the difference between two groups has no statistically significant. The LAMP group was divided into two subgroups: (1) ACS(+)(n=11) comprising patients who had ACS after surgery, and (2) ACS(-) (n=53) comprising patients without ACS. At the latest follow?up, the average JOA score of pa?tients with anterior residual compression of spinal cord was 10.85±5.46, while the average JOA score of patients without anterior residual compression of spinal cord was 14.18 ± 4.52. The recovery rate differed significantly between the ACS(+) and ACS(-) groups, 40.52%±9.76% and 70.38%±10.52%, respectively. Also at the latest follow?up, the cervical curvature, ROM and ROM loss angle were 10.2°±7.3°, 15.6°±6.7°and 11.8°±8.3°in the group with anterior residual compression of spinal cord, respective?ly. The groups without anterior residual compression of spinal cord were 15.8°±6.5°, 20.4°±10.2°and 8.8°±6.8°, respectively. Conclusion Both ADF and LAMP groups provided good outcomes at 2?year time?point whereas ADF could achieve more satis?factory outcomes and better sagittal alignment at the middle?term. ADF can remove the compression directly, maintain the curva?ture of cervical vertebra effectively and restore the nerve function well. The clinical outcomes after LAMP could be influenced by ACS, due to the reduction of cervical curvature and the decrease of cervical range of motion.
摘要
Objective To investigate the effect of 3-bromopyruvate (3-BrPA) on transplanted rectal tumors in experimental rabbit models. Methods A total of 60 New Zealand white rabbits with transplanted rectal tumor were randomly and equally divided into low-dose (0.5 mmol/L), medium-dose (1.0 mmol/L), high-dose (2.0 mmol/L) treatment groups and saline control group with 15 rabbits in each group. Arterial perfusion of 10 ml 3-BrPA with concentration of 0.5 mmol/L, 1.0 mmol/L and 2.0 mmol/L via caudal mesenteric artery was respectively employed for the rabbits of the corresponding treatment group; the control group was perfused with equal amounts of saline. Four days later, rectal tumors were removed by vivisection. The necrosis degree of tumor cells was determined by microscopic examination, and the necrosis rate was calculated. The effect of different 3-BrPA concentrations on the rectal tumor was evaluated. Results The rectal tumor transplantation and transcatheter 3-BrPA or saline perfusion was successfully completed in all 60 experimental rabbits. Microscopically, tumor cells showed different degrees of damage in experimental rabbits. In low-dose (0.5 mmol/L) treatment group, gradeⅠnecrosis was observed in 3 rabbits, gradeⅡin 11 rabbits, and gradeⅢin one rabbit;the effective rate was 6.7%. In medium-dose (1.0 mmol/L) treatment group, gradeⅡnecrosis was seen in 2 rabbits, grade Ⅲ in 10 rabbits, and grade Ⅳ in 3 rabbits; the effective rate was 86.6%. In high-dose (2.0 mmol/L) treatment group, gradeⅢnecrosis was detected in 2 rabbits and gradeⅣin 13 rabbits;the effective rate was 100.0%. In the saline control group, grade I necrosis was observed in 15 rabbits. Statistically significant differences in tumor necrosis rate and effective rate existed between medium-dose (1.0 mmol/L) treatment group and high-dose (2.0 mmol/L) treatment group (P<0.05). Statistically significant differences in tumor necrosis rate also existed between each other among the four groups with necrosis of gradeⅠto gradeⅣ(P<0.05). 3-BrPA had obvious therapeutic effect, while it showed no damage to the normal intestinal tissue. Conclusion For the treatment of transplanted rectal tumor in rabbit models, arterial infusion of 3-BrPA has certain therapeutic effect. In the high-dose group, the necrosis rate and effective rate are the highest, and the therapeutic results are the most significant.
摘要
Objective: By constructing the cash flow model, it proposed the premium adjustment mechanism of critical illness insurance(CII). Methods: Based on the practical data of critical illness insurance in China, it established some actuarial assumptions and cash flow model to simulate and analyze premium adjustment mechanism of CII. Results: ( 1) Because of the deterioration of critical illness incidence rate and the change of market interest rates , CII guaranteed premium usually resents pricing risk, which showed that the cash flow is negative, sometimes accumulated cash is negative; (2) based on the criteria of insurance cost adjustment, it is suggested that when the loss rate reached more than 70%, which could permit the insurance company adjust the premium, if the loss rate reached more than 80%, it needs to compulsory the insurance companies to adjust premium. Conclusion: The study proposes the mechanism of CII premium adjustment, provides guidance for practice.
摘要
Objective To explore the regulation of ROS level and ROS-triggered downstream events on SK-N-MC Ewing sarcoma cells upon apoptasis induction by 2-Methoxyestradiol (2-ME). Methods To detect the reversibility of apoptosis and the alternation of activity of respiratory chain, mitechondria transmembrane potential (△ψm), and cellular ROS level and to explore their association with flow cytometry, clark oxygen electronic node analysis, drug-removal design, and permeability transition (PT) pore stablizing agent. Results SK-N-MC cells were induced to ROS-dependent apoptosis. Apoptosis occured irreversibly after2-ME treatment for 3 h. Upon 2-ME treatment, the activity of respiratory chain was inhibited and the ROS generation was accelerated; the △ψm underwent the increasing within 3h but decreasing after 3h which could be reversed by PT pore stablizing; the ROS level underwent the continuous increasing and PT pore stablizing had no obvious effect on it. Conclusion 2-ME causes the acceleration of ROS generation via inhibiting the activity of respiratory chain and elevating the level of △ψm. ROS plays a signaling role and when total ROS accumulate to a threshold, the PT pore opening and the collapse of △ψm could be induced irreversibly and cell is eventually introduced to death.
摘要
Objective To study the pharmacodynamics features of cisatracurium besylate in differ-ent age patients. Methods One hundred and eighty patients were randomized to group Ⅰ (50-60 years old),group Ⅱ (61-70 years old)and group Ⅲ (above 70 years old).Each group was subdivided according to the dose of cisatracurium besylate, 0.10 mg/kg (2ED95)or 0.15 mg/kg (3ED95) into group Ⅰ2, Ⅰ3, Ⅱ2, Ⅱ3,Ⅲ2, Ⅲ3(n = 30).ECG, SpO2, PETCO2, HR and neuromuscular blockade were monitored. Intubation conditions were assessed when T1 was zero after cisatracurium besylate administer ration using a 4-part scale.The onset time, TOF no reaction time, duration time, recovery lime and hemodynamic response time were recorded. Re-sults The onset times of group Ⅰ3, Ⅱ3 and Ⅲ3 were significantly shorter than those of group Ⅰ2, Ⅱ2 and Ⅲ2 (P < 0.05).The percentages of patients with excellent intubation condition in group Ⅰ3, Ⅱ3 and Ⅲ3 were 93%, 90%, and 80%, which were markedly higher than those in group Ⅰ2, Ⅱ2 and Ⅲ2 (67%, 60%, 60%). TOF no reaction time and duration time were longer in group Ⅰ3, Ⅱ3 and Ⅲ3 than those in group Ⅰ2, Ⅱ2 and Ⅲ2. There was no significant difference in muscle chalasis among the six groups. Conclusions Cisatracuri-um besylate 0.15 mg/kg produces quicker onset time and acceptable intubation conditions in the different age patients than 0.10 mg/kg. Recovery time is independent on the dosage and age. Aging has no influence on the phannacodynamics of single injection of cisatracurium besylate.