Pharmacodynamics and mechanism of Erigeron breviscapus granules in the treatment of ischemic stroke in mice by regulating sphingolipid metabolism based on metabolomics.

AIM: Erigeron breviscapus (Vant.) Hand.-Mazz. (EB) granules is the extract preparation of EB, with clear curative effect and unclear mechanism. This study intends to systematically explore the specific mechanism of EB granules in the treatment of IS from the metabolic perspective. METHODS: The model of transient middle cerebral artery occlusion (tMCAO) in mice was established by the suture-occluded method. The therapeutic effect of EB granules on tMCAO mice was evaluated by behavioral evaluation, brain water content determination, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and levels of lactate dehydrogenase (LDH) and neuron specific enolase (NSE) in serum. In order to screen differential metabolites, non-targeted metabolomics technology was used to detect the metabolites in serum before and after administration. Univariate statistics, multivariate statistics and bioinformatics were used to analyze the changes of metabolites in serum of tMCAO mice. The possible related mechanism of EB granules in treating IS was screened by pathway enrichment analysis, and the preliminary verification was carried out at animal level by enzyme linked immunosorbent assay (ELISA) and western blot (WB). RESULTS: EB granules could significantly improve behavior of tMCAO mice, reduce brain water content and cerebral infarction volume, improve morphology of brain tissue, reduce the levels of LDH and NSE in serum. A total of 232 differential metabolites were screened, which were mainly enriched in many biological processes such as sphingolipid metabolism. The differential metabolite S1P and its receptors S1PR1 and S1PR2 in sphingolipid metabolism were verified. The results showed that the level of S1P in brain tissue increased and the protein expression of S1PR1 decreased significantly after modeling, and reversed after administration, but there was no significant difference in the protein expression of S1PR2. CONCLUSION: The therapeutic effects of EB granules may be related to affecting sphingolipid metabolism through regulating S1P/S1PR1.

Pharmacodynamics and Mechanism of Astragali Radix and Anemarrhenae Rhizoma in Treating Chronic Heart Failure by Inhibiting Complement Activation.

Astragali radix (AR) and anemarrhenae rhizoma (AAR) are used clinically in Chinese medicine for the treatment of chronic heart failure (CHF), but the exact therapeutic mechanism is unclear. In this study, a total of 60 male C57BL/6 mice were divided into 5 groups, namely sham, model, AR, AAR, and AR-AAR. In the sham group, the chest was opened without ligation. In the other groups, the chest was opened and the transverse aorta was ligated to construct the transverse aortic constriction model. After 8 weeks of feeding, mice were given medicines by gavage for 4 weeks. Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were detected by echocardiography. Heart weight index (HWI) and wheat germ agglutinin staining were used to evaluate cardiac hypertrophy. Hematoxylin-eosin staining was used to observe the pathological morphology of myocardial tissue. Masson staining was used to evaluate myocardial fibrosis. The content of serum brain natriuretic peptide (BNP) was detected by enzyme-linked immunosorbent assay kit. The content of serum immunoglobulin G (IgG) was detected by immunoturbidimetry. The mechanism of AR-AAR in the treatment of CHF was explored by proteomics. Western blot was used to detect the protein expressions of complement component 1s (C1s), complement component 9 (C9), and terminal complement complex 5b-9 (C5b-9). The results show that AR-AAR inhibits the expression of complement proteins C1s, C9, and C5b-9 by inhibiting the production of IgG antibodies from B cell activation, which further inhibits the complement activation, attenuates myocardial fibrosis, reduces HWI and cardiomyocyte cross-sectional area, improves cardiomyocyte injury, reduces serum BNP release, elevates LVEF and LVFS, improves cardiac function, and exerts myocardial protection.

Analysis of factors influencing the intravertebral shell phenomenon after posterior reduction internal fixation of thoracolumbar fracture: a retrospective study.

STUDY DESIGN: A retrospective study. PURPOSE: The study objectives were as follows: 1) to analyze the factors influencing the occurrence of the intravertebral shell phenomenon (ISP) after thoracolumbar spinal fracture surgery and the evolutionary outcome of this phenomenon; and 2) to make recommendations for the clinical prevention and treatment of ISP. METHODS: We retrospectively analyzed 331 patients with single-segment fractures of the thoracolumbar spine treated with internal fixation via a pedicle screw-rod system. Univariate and multivariate logistic regression were used to analyze factors influencing ISP. RESULTS: A total of 260 patients (78.5%) developed ISP after surgery. Reduced bone mineral density, screw insertion depth, degree of vertebral body injury, and excessive vertebral body spreading were significantly associated with the occurrence of ISP (P < 0.05). A total of 166 of the 260 patients were reviewed via CT at 1 year postoperatively. Among them, 104 patients (62.6%) showed shrinkage or healed vertebral cavities, and 62 patients (37.4%) showed enlarged vertebral cavities or collapsed endplates. CONCLUSION: In clinical management, surgeons need to focus on risk factors for ISP, which include decreased bone density, preoperative vertebral overcompression, intraoperative vertebral overextension, screw insertion depth, and the degree of vertebral repositioning. At the 1-year postoperative follow-up, some of the vertebrae with ISP failed to heal or even showed vertebral cleft enlargement, which would affect the stability of the internal fracture fixation device and the quality of the patient's daily life.

A Digital Twin Lake Framework for Monitoring and Management of Harmful Algal Blooms.

Harmful algal blooms (HABs) caused by lake eutrophication and climate change have become one of the most serious problems for the global water environment. Timely and comprehensive data on HABs are essential for their scientific management, a need unmet by traditional methods. This study constructed a novel digital twin lake framework (DTLF) aiming to integrate, represent and analyze multi-source monitoring data on HABs and water quality, so as to support the prevention and control of HABs. In this framework, different from traditional research, browser-based front ends were used to execute the video-based HAB monitoring process, and real-time monitoring in the real sense was realized. On this basis, multi-source monitored results of HABs and water quality were integrated and displayed in the constructed DTLF, and information on HABs and water quality can be grasped comprehensively, visualized realistically and analyzed precisely. Experimental results demonstrate the satisfying frequency of video-based HAB monitoring (once per second) and the valuable results of multi-source data integration and analysis for HAB management. This study demonstrated the high value of the constructed DTLF in accurate monitoring and scientific management of HABs in lakes.

Saponin of Aralia taibaiensis promotes angiogenesis through VEGF/VEGFR2 signaling pathway in cerebral ischemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Aralia taibaiensis is known for its ability to promote blood circulation and dispel blood stasis, activate meridians and remove arthralgia. The saponins of Aralia taibaiensis (sAT) are the main active components that are often used to treat cardiovascular and cerebrovascular diseases. However, it has not been reported whether sAT can improve ischemic stroke (IS) by promoting angiogenesis. AIM OF THE STUDY: In this study, we investigated the potential of sAT to promote post-ischemic angiogenesis in mice and determined the underlying mechanism through in vitro experiments. METHODS: To establish the middle cerebral artery occlusion (MCAO) mice model in vivo. First of all, we examined the neurological function, brain infarct volume, and degree of brain swelling in MCAO mice. We also observed pathological changes in brain tissue, ultrastructural changes in blood vessels and neurons, and the degree of vascular neovascularization. Additionally, we established the oxygen-glucose deprivation/reoxygenation (OGD/R) -human umbilical vein endothelial cells (HUVECs) model in vitro to detect the survival, proliferation, migration and tube formation of OGD/R HUVECs. Finally, we verified the regulatory mechanism of Src and PLCγ1 siRNA on sAT promoting angiogenesis by cell transfection technique. RESULTS: In the cerebral ischemia-reperfusion mice, sAT distinctly improved the cerebral infarct volume, brain swelling degree, neurological dysfunction, and brain histopathological morphology due to cerebral ischemia/reperfusion injury. It also increased the double positive expression of BrdU and CD31 in brain tissue, promoted the release of VEGF and NO and decreased the release of NSE and LDH. In the OGD/R HUVECs, sAT significantly improved cell survival, proliferation, migration and tube formation, promoted the release of VEGF and NO, and increased the expression of VEGF, VEGFR2, PLCγ1, ERK1/2, Src and eNOS. Surprisingly, the effect of sAT on angiogenesis was inhibited by Src siRNA and PLCγ1 siRNA in OGD/R HUVECs. CONCLUSION: The results proved that sAT promotes angiogenesis in cerebral ischemia-reperfusion mice and its mechanism is to regulate VEGF/VEGFR2 and then regulate Src/eNOS and PLCγ1/ERK1/2.

Surgical interventions for cervical spondylosis due to ossification of posterior longitudinal ligament: A meta-analysis.

BACKGROUND: Aim of this study was to evaluate the effectiveness of various surgical interventions for the management of cervical spondylosis due to the ossification of posterior longitudinal ligament (OPLL). METHODS: After a comprehensive literature search in electronic databases, studies were selected by following pre-determined eligibility criteria. Random effects meta-analyses were performed to estimate the effect sizes of various surgical approaches in improving Japanese Orthopedic Association (JOA) scores at latest follow-up and meta-regression analyses were carried out to examine the factors affecting the change in JOA score. RESULTS: Twenty-three studies [1576 patients; 57.83 (95% confidence interval, 95% CI: 55.98-59.68] years of age; and 73 (70-76) % males; follow-up 55.4 ±â€Š25.7 (range 12-170) months] were included in the meta-analysis. All surgical interventions significantly (P < .00001) improved JOA score. Anterior surgical approaches had an effect size of 4.80 [4.10-5.50] and posterior approaches with laminectomy and laminoplasty improved JOA score by 3.57 [2.39-4.75] and 3.99 [3.65-4.32], respectively. Improvement in JOA score was significantly inversely related to the preoperative JOA score (P < .00001). Surgical interventions did not significantly affect cervical lordosis at the latest follow-up. CONCLUSION: Surgical interventions for cervical spondylosis due to OPLL significantly improve JOA score as observed at the latest follow-up and this is found to be significantly inversely associated with preoperative JOA score.

[Technology of minimally invasive percutancous plate osteosynthesis for the treatment of fractures of the distal tibia].

OBJECTIVE: To explore the technique and clinical results of minimally invasive percutancous plate osteosynthesis (MIPPO) for the treatment of fractures of the distal tibia. METHODS: A retrospective study was conducted to analyze 65 patients with the distal tibia fractures who had been treated with MIPPO. The average age of the patients was 35 years old (ranging from 13 to 75). There were 42 males and 23 females. According to AO fracture classification for the distal tibial fractures, there were 5 cases of type-A1 fracture, 22 type-A2, 32 type-A3 and 6 type-C1. RESULTS: All the patients were followed up and ranged from 6 to 18 months (averaged 11 months). All the fractures showed union. The time required for the bony union ranged from 3 to 6 months (averaged 4.5 months). The patients were evaluated with respect to functional recovery according to Mazur Grating System for the Ankle. Forty patients obtained excellent results, 19 good and 6 fair. The total satisfactory rate was 90.7%. CONCLUSION: The technology of minimally invasive percutancous plate osteosynthesis (MIPPO)is a safe and effective procedure for the distal tibial fractures with the benefits of limited invasion,less complications and high rate of bone union.