Efficacy and Safety of Bushen Huoxue Formula in Patients with Discogenic Low-Back Pain: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: To assess the efficacy and safety of Bushen Huoxue Formula (BSHXF) for the treatment of discogenic low-back pain (DLBP). METHODS: This was a parallel, double-blind, randomized, clinical trial performed between May 2019 and June 2020. Seventy patients were assigned by computerized random number table to the treatment group (lumbar traction and BSHXF, 35 cases) or the control group (lumbar traction and placebo, 35 cases). The patients received intervention for 3 weeks. Assessment was conducted before treatment and at week 1, 2, 3 during treatment. Primary outcome was the self-reported score of Oswestry Disability Index (ODI). Secondary outcomes included Visual Analog Scale (VAS), clinical efficacy rate by minimal clinically important difference (MCID) as well as lumbar tenderness, muscle tone and lumbar spine mobility. Adverse reactions were recorded. Follow-up was performed at 1 and 3 months after the end of treatment. RESULTS: In the treatment group, ODI score was significantly decreased compared with baseline (P<0.05) and the control group at 2- and 3- week treatment. Similarly, VAS score decreased compared with the baseline (P<0.05) and was lower than that in the control group at 2- and 3- week treatment (P<0.05). The clinical efficacy rate of the treatment group was higher than that of the control group after treatment [32.35% (11/34) vs. 3.13% (1/32), P<0.05). Moreover, the tenderness, and muscle tone, as well as the back extension and left flexion in lumbar spine mobility in the treatment group at 3-week treatment were significantly improved compared with the control group (P<0.05). Follow-up showed that at 1-month after treatment, the treatment group had better outcomes than the control group with regard to a total score of ODI and VAS scores, as well as clinical efficacy rate (all P<0.05). Moreover, VAS score was still significantly lower than the control group at 3-month follow-up (P<0.05). No adverse reactions were reported during the study. CONCLUSION: BSXHF combined with lumbar traction can significantly improve the clinical symptoms including pain intensity, functionality, muscle tone, and lumbar spine mobility in DLBP patients. (Registration No. ChiCTR1900027777).

[Research progress in mechanism of Chinese herbal compounds and monomers in delaying lumbar intervertebral disc degeneration].

Traditional Chinese medicine has unique advantages in the treatment of degenerative bone and joint diseases, and its widely used in clinical practice. In recent years, many scholars have conducted a large number of basic studies on the delay of intervertebral disc degeneration by herbal compound and monomeric components from different perspectives. In order to further elucidate its mechanism of action, this paper summarizes the in vivo and in vitro experimental studies conducted at the level of both herbal compound and single components, respectively, in order to provide references for the basic research on the treatment of lumbar intervertebral disc degeneration by Chinese medicine. A summary shows that commonly used herbal compound prescriptions include both classical prescriptions such as Duhuo Jisheng Decoction, as well as clinical experience prescriptions such as Yiqi Huoxue Recipe. Angelicae Sinensis Radix, Chuanxiong Rhizoma, Rehmanniae Radix Praeparata, Achyranthis Bidentatae Radix, and Eucommiae Cortex were used most frequently. Tonic for deficiency and blood stasis activators were used most frequently. The most utilized monomeric components include icariin, ginsenoside Re, salvianolic acid B and aucubin. The main molecular mechanisms by which herbal compound and monomeric components delay of lumbar intervertebral disc degeneration include improving the intervertebral disc microenvironment, promoting the synthesis of aggregated proteoglycans and type Ⅱ collagen in the intervertebral disc, reducing the degradation of the extracellular matrix, and inhibiting apoptosis in the nucleus pulposus cells, etc. The main signaling pathways involved include Wnt/ß-catenin signaling pathway, MAPK-related signaling pathway, mTOR signaling pathway, Fas/FasL signaling pathway, PI3 K/Akt signaling pathway, NF-κB signaling pathway, JAK/STAT signaling pathway, and hedgehog signaling pathway, etc.

Differentiation Antagonizing Non-protein Coding RNA Knockdown Alleviates Lipopolysaccharide-Induced Inflammatory Injury and Apoptosis in Human Chondrocyte Primary Chondrocyte Cells Through Upregulating miRNA-19a-3p.

OBJECTIVE: To confirm the role of long noncoding RNA differentiation antagonizing non-protein coding RNA (DANCR) in chondrocyte inflammatory injury in osteoarthritis (OA) in vitro, as well as its molecular mechanism. METHODS: Human primary chondrocytes were treated with lipopolysaccharide (LPS) to construct a chondrocyte inflammatory injury in human OA cell model. Gene expression was detected using real-time quantitative polymerase chain reaction. Cell inflammatory injury was evaluated by Cell Counting Kit-8 assay, flow cytometry, and enzyme-linked immunosorbent assay. The interplay between miRNA-19a-3p (miR-19a) and DANCR was validated by dual-luciferase reporter assay and RNA immunoprecipitation. RESULTS: Expression of DANCR was upregulated, and miR-19a was downregulated in human OA cartilage and LPS-treated primary chondrocytes in vitro. Moreover, DANCR expression was inversely correlated with miR-19a in OA patients. LPS reduced cell viability and increased the apoptotic rate and secretion of interleukin (IL)-1ß, IL-6, IL-8, as well as tumor necrosis factor (TNF)-α in primary chondrocyte cells in vitro, suggesting an inflammatory injury model of OA. Functionally, knockdown of DANCR could attenuate LPS-induced apoptosis and inflammatory response, as evidenced by improved cell viability, and reduced apoptotic rate and products of IL-1ß, IL-6, IL-8, and TNF-α. Notably, DANCR negatively regulated miR-19a expression, presumably via sponging. Furthermore, miR-19a deletion eliminated the effect of DANCR knockdown on apoptosis and the inflammatory response of primary chondrocytes under LPS stress. CONCLUSION: Differentiation antagonizing non-protein coding RNA silencing could protect human chondrocyte cells against LPS-induced inflammatory injury and apoptosis through targeting miR-19a, suggesting a vital role of the DANCR/miR-19a axis in OA.

Effects of Axial Compression and Distraction on Vascular Bud and VEGFA Expression in the Vertebral Endplate of an Ex Vivo Rabbit Spinal Motion Segment Culture Model.

STUDY DESIGN: An ex vivo study of the rabbit's vertebral endplate. OBJECTIVE: The aim of this study was to assess the effect of axial compression and distraction on vascular buds and vascular endothelial growth factor (VEGFA) expression of the vertebral endplate (VEP). SUMMARY OF BACKGROUND DATA: The abnormal load can lead to intervertebral disc degeneration (IDD), whereas axial distraction can delay this process. The effects of different mechanical loads on the intervertebral disc (IVD) have been hypothesized to be related to changes in the vascular buds of the VEP; moreover, the process that might involve the vascular endothelial growth factor (VEGF) within the VEP. METHODS: Rabbit spinal segments (n = 40) were harvested and randomly classified into four groups: Control group, no stress was applied; Group A, a constant compressive load applied; Group B, compression load removed for a fixed time daily on a continuous basis, and substituted with a distraction load for 30 minutes; and Group C, compression removed for 30 minutes for a fixed period daily on a continuous basis. Tissue specimens were collected before the culture (day 0) and on day 14 post-culture of each group for analysis of IVDs' morphology, and protein and mRNA expression of Aggrecan, COL2al, VEGFA, and vascular endothelial growth factor receptor 2 of the VEPs. RESULTS: Application of axial distraction and dynamic load compression significantly delayed time- and constant compression-mediated VEP changes and IDD. Moreover, the degree of degeneration was associated with loss of vascular buds, as well as the downregulation of VEGFA and its receptor. CONCLUSION: The regulation of vascular buds and VEGF expression in the VEP represents one of the mechanisms of axial distraction and dynamic loading.Level of Evidence: N/A.

Constant compression decreases vascular bud and VEGFA expression in a rabbit vertebral endplate ex vivo culture model.

SUMMARY OF BACKGROUND DATA: The vascular buds in the vertebral endplate (VEP) are the structural foundation of nutrient exchange in the intervertebral disc (IVD). VEGF is closely related to angiogenesis in the endplate and intervertebral disc degeneration (IDD). OBJECTIVE: To investigate the effects of static load on vascular buds and VEGF expression in the VEP and to further clarify the relation between IDD and VEGF. METHODS: IVD motion segments were harvested from rabbit lumbar spines and cultured under no-loading conditions (controls) or in custom-made apparatuses under a constant compressive load (0.5 MPa) for up to 14 days. Tissue integrity and the number of vascular buds were determined, and the concentrations and expression of Aggrecan, COL2a1, and VEGFA in the VEPs were assessed after 3, 7, and 14 days of culturing and then compared with those of fresh tissues. RESULTS: Under the constant compression, the morphological integrity of the VEPs was gradually disrupted, and immunohistochemistry results showed a significant decrease in the levels of Agg and COL2a1. During the static load, the number of vascular buds in the VEPs was gradually reduced from the early stage of culture, and ELISA showed that the constant compressive load caused a significant decrease in the VEGFA and VEGFR2 protein concentrations, which were consistent with the immunohistochemistry results. Western blot and RT-PCR results also showed that the loading state caused a significant decrease in VEGFA expression compared with that of fresh and control samples. CONCLUSIONS: Constant compression caused degeneration of the VEP as well as a decreased number of vascular buds, thereby accelerating disc degeneration. VEGFA is involved in this process. We anticipate that regulating the expression of VEGFA may improve the condition of the lesions to the vascular buds in the endplates, thus enhancing the nutritional supply function in IVD and providing new therapeutic targets and strategies for the effective prevention and treatment of IDD.