[Antidepressant mechanism of Shenling Kaixin Granules based on BDNF/TrkB/CREB pathway].

To investigate the antidepressant mechanism of Shenling Kaixin Granules(SLKX) in treating chronic unpredictable mild stress(CUMS) model rats. Ninety male SD rats were randomly divided into control group, model group, Shugan Jieyu Capsules(110 mg·kg~(-1)) group and SLKX low-(90 mg·kg~(-1)), medium-(180 mg·kg~(-1)), and high-dose(360 mg·kg~(-1)) groups. Depression rat model was replicated by CUMS method. After treatment, the behavioral changes of rats were evaluated by sugar preference, open field, elevated cross maze and forced swimming experiments. The contents of interleukin 1 beta(IL-1ß), tumor necrosis factor α(TNF-α), brain-derived neurotrophic factor(BDNF) and 5-hydroxytryptamine(5-HT) in serum were determined by enzyme linked immunosorbent assay(ELISA), and the activities of superoxide dismutase(SOD) and catalase(CAT) in hippocampal CA1 region were also detected. Pathological changes in hippocampal CA1 region were detected by hematoxylin-eosin(HE) staining, and Western blot was used to determine the expression of nerve growth factor(NGF), BDNF, phospho-tyrosine kinase receptor(p-TrkB)/TrkB, phospho-cAMP-response element binding protein(p-CREB)/CREB, nuclear factor E2 related factor 2(Nrf2), heme oxygenase 1(HO-1), B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax) and caspase-3 in hippocampal CA1 region. RESULTS:: showed that compared with the control group, the model group had decreased sugar preference, reduced number of entries and time spent in the center of open field and shortened total distance of movement, reduced number of entries and proportion of time spent in open arm, and increased number and time of immobility in forced swimming experiment. Additionally, the serum contents of IL-1ß and TNF-α and the expression of caspase-3 were higher, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1 and Bcl-2/Bax, and the Nrf2 nuclear translocation were lower in model group than in control group. Compared with the conditions in model group, the sugar preference, the number of entries and time spent in the center of open, total distance of movement, and the number of entries and proportion of time spent in open arm in treatment groups were increased while the number and time of immobility in forced swimming experiment were decreased; the serum contents of IL-1ß and TNF-α and the expression of caspase-3 were down regulated, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1, Bcl-2/Bax, and Nrf2 nuclear translocation were enhanced. In conclusion, SLKX might regulate the Nrf2 nucleus translocation by activating BDNF/TrkB/CREB pathway, lower oxidative stress damage in hippocampus, inhibit caspase-3 activity, and reduce apoptosis of hippocampal nerve cells, thereby playing an antidepressant role.

[Neuroprotective effect of ginsenoside Re on drosophila model of Parkinson's disease].

This study aims to explore the neuroprotective mechanism of ginsenoside Re(GS-Re) on drosophila model of Parkinson's disease(PD) induced by rotenone(Rot). To be specific, Rot was used to induce PD in drosophilas. Then the drosophilas were grouped and respectively treated(GS-Re: 0.1, 0.4, 1.6 mmol·L~(-1); L-dopa: 80 µmol·L~(-1)). Life span and crawling ability of drosophilas were determined. The brain antioxidant activity [content of catalase(CAT), malondialdehyde(MDA), reactive oxygen species(ROS), superoxide dismutase(SOD)], dopamine(DA) content, and mitochondrial function [content of adenosine triphosphate(ATP), NADH:ubiquinone oxidoreductase subunit B8(NDUFB8) Ⅰ activity, succinate dehydrogenase complex, subunit B(SDHB) Ⅱ activity] were detected by enzyme-linked immunosorbent assay(ELISA). The number of DA neurons in the brains of drosophilas was measured with the immunofluorescence method. The levels of NDUFB8 Ⅰ, SDHB Ⅱ, cytochrome C(Cyt C), nuclear factor-E2-related factor 2(Nrf2), heme oxygenase-1(HO-1), B-cell lymphoma/leukemia 2(Bcl-2)/Bcl-2-assaciated X protein(Bax), and cleaved caspase-3/caspase-3 in the brain were detected by Western blot. The results showed that model group [475 µmol·L~(-1) Rot(IC_(50))] demonstrated significantly low survival rate, obvious dyskinesia, small number of neurons and low DA content in the brain, high ROS level and MDA content, low content of SOD and CAT, significantly low ATP content, NDUFB8 Ⅰ activity, and SDHB Ⅱ activity, significantly low expression of NDUFB8 Ⅰ, SDHB Ⅱ, and Bcl-2/Bax, large amount of Cyt C released from mitochondria to cytoplasm, low nuclear transfer of Nrf2, and significantly high expression of cleaved caspase-3/caspase-3 compared with the control group. GS-Re(0.1, 0.4, and 1.6 mmol·L~(-1)) significantly improved the survival rate of PD drosophilas, alleviated the dyskinesia, increased DA content, reduced the loss of DA neurons, ROS level, and MDA content in brain, improved content of SOD and CAT and antioxidant activity in brain, maintained mitochondrial homeostasis(significantly increased ATP content and activity of NDUFB8 Ⅰ and SDHB Ⅱ, significantly up-regulated expression of NDUFB8 Ⅰ, SDHB Ⅱ, and Bcl-2/Bax), significantly reduced the expression of Cyt C, increased the nuclear transfer of Nrf2, and down-regulated the expression of cleaved caspase-3/caspase-3. In conclusion, GS-Re can significantly relieve the Rot-induced cerebral neurotoxicity in drosophilas. The mechanism may be that GS-Re activates Keap1-Nrf2-ARE signaling pathway by maintaining mitochondrial homeostasis, improves antioxidant capacity of brain neurons, then inhibits mitochondria-mediated caspase-3 signaling pathway, and the apoptosis of neuronal cells, thereby exerting the neuroprotective effect.

Comparisons between Direct Anterior Approach and Lateral Approach for Primary Total Hip Arthroplasty in Postoperative Orthopaedic Complications: A Systematic Review and Meta-Analysis.

The direct anterior approach (DAA) are attracting increasing attention from orthopedic arthroplasty surgeons, due to the less blood loss, mild soft tissue invasion, rapid rehabilitation and shorter length of stay. However, the longer learning curve in DAA can give rise to several complications, such as intraoperative femoral fracture, lateral femoral cutaneous nerve injury, wound-healing problem, premature revision and so on. This meta-analysis was performed to compare the rate of postoperative orthopedic complications between the DAA and the lateral approach (LA). All studies involving the comparison of postoperative orthopedic complications after THA between the DAA and LA group were searched in 7 databases prior to October 2020. The odds ratio (OR) with the 95% confidence intervals (CI) for each outcome was calculated by using the RevMan 5.3. The methodological bias of included studies was evaluated and the potential heterogeneity sources were analyzed. Thirteen comparative studies including a total of 24853 hips (9575 hips in the DAA group and 15278 hips in the LA group) were eligible for this meta-analysis. There was no significant difference in the rate of surgical site infection [2.59% vs 2.14% (OR = 0.98; 95% CI: 0.59-1.61, P = 0.93)], heterotopic ossification [12.16% vs 26.47% (OR = 0.46; 95% CI: 0.20-1.07, P = 0.07)] and reoperation [2.70% and 2.11% respectively (OR = 0.93; 95% CI: 0.68-1.26, P = 0.64)] between the DAA and LA groups. Although a lower rate in prosthesis malposition [36.19% vs 54.86% (OR = 0.50; 95% CI: 0.35-0.73, P = 0.0003)], leg length discrepancy [1.87% vs 2.37% (OR = 2.35; 95% CI: 1.30-4.25, P = 0.005)] and Trendelenburg gait [1.68% vs 4.78% (OR = 0.29; 95% CI: 0.13-0.65, P = 0.003)] was observed in the DAA group, a higher rate in dislocation [0.77% vs 0.18% (OR = 3.73; 95% CI: 2.35-5.94, P< 0.00001)], periprosthetic fracture [1.05% vs 0.41% (OR = 2.38; 95% CI: 1.58-3.58, P< 0.0001)], prosthesis loosening [0.61% vs 0.37% (OR = 1.66; 95% CI: 1.05-2.62, P = 0.03)] and nerve injury [0.95% vs 0% (OR = 7.12; 95% CI: 1.66-30.48, P = 0.008)] was found in the DAA group. This meta-analysis demonstrated several evidences indicating that the DAA exhibited the advantages in the accurate prosthesis placement and less damage of surrounding hip musculature. However, a higher rate in dislocation, periprosthetic fracture, prosthesis loosening and nerve injury in the DAA group should be paid more attention, due to the limited exposure and a longer learning curve, compared to the LA.