Traditional Chinese Medicine formula Bu-Shen-Huo-Xue-Fang (BSHXF) protects nucleus pulposus cells against the inflammatory and oxidative stress-induced degenerative changes.

Degeneration of the intervertebral disc is primarily caused by the loss of nucleus pulposus cells (NPCs) and extracellular matrix (ECM) (IDD). Bu-Shen-Huo-Xue-Fang (BSHXF), a traditional Chinese medicine decoction, has been used to treat IDD in clinical; nevertheless, the active components and underlying molecular mechanisms remain unknown. BSHXF improved IL-1ß and H2O2 stimulation-induced injuries on NPCs by promoting cell viability, increasing ECM deposition, inhibiting cell senescence, and decreasing the levels of inflammatory factors. The active ingredients in BSHXF were identified by LC-MS/MS analysis; three active ingredients from the principal drugs, Aucubin, Tanshinol, and Tanshinone II A promoted NPC viability; and Aucubin and Tanshinol promoted NPC viability more. Aucubin and Tanshinol, respectively, improved H2O2 stimulation-induced injuries on NPCs by promoting cell viability, increasing ECM deposition, inhibiting cell senescence, and decreasing the levels of inflammatory factors. The activator of NF-κB and Wnt signaling pathways attenuated Aucubin and Tanshinol's protective effects by promoting ECM degradation and NPC senescence. Aucubin, Tanshinol, and Tanshinone II A were identified as the most potent compounds in BSHXF protection against degenerative changes in NPCs. The NF-κB and Wnt signaling pathways might be involved in the protective effects of Aucubin and Tanshinol against H2O2-induced degenerative changes.

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).

Application of Intelligent Exercise Training Equipment in Clinical Nursing of Neurology Department.

To investigate the effect of intelligent exercise training equipment on lower limb function and standing stability of stroke patients with hemiplegia in clinical nursing of neurology department. Forty-eight stroke patients with a course of 1 to 3 months were randomly divided into treatment group and control group, with 24 cases in each group. The control group was treated with conventional rehabilitation training, and the treatment group was treated with intelligent training system, twice a day, 20 min each time. Lower extremity motor function (using the FMA-L scale) and walking function (using the functional walking scale FAC) were assessed before treatment and 4 weeks after treatment. The results showed that there was no statistical difference between the control group and the treatment group in the t-test of lower limb motor function scores before rehabilitation treatment (P > 0.05). After treatment, the lower extremity motor function scores of the two groups were tested by group design T-test, and the results showed that there was a significant difference between the two groups (P < 0.05); The effect of the treatment group was significantly better than that of the control group (P < 0.05). Intelligent exercise training equipment combined with routine rehabilitation therapy in clinical nursing of neurology department could improve the lower extremity motor function and walking ability of patients with convalescence stroke hemiplegia, and the effect was better than that of routine rehabilitation therapy alone.

A Synergistic DNA-polydopamine-MnO2 Nanocomplex for Near-Infrared-Light-Powered DNAzyme-Mediated Gene Therapy.

DNAzyme is emerging for gene therapy. The administration of the in vivo catalytic activity of DNAzyme has proven important but challenging for clinical applications. Herein, we report a synergistic DNA-polydopamine-MnO2 nanocomplex, which enables near-infrared (NIR)-light-powered catalytic activity of DNAzyme in vivo. The nanocomplex has a hierarchical structure: a DNA nanoframework as the scaffold and polydopamine-MnO2 (PM) as the coating layer. The DNA nanoframework contains repeated DNAzyme sequences. PM assembles on the surface of the DNA nanoframework. When the nanocomplex accumulates at tumor sites, upon NIR-light radiation, polydopamine induces a temperature elevation at tumor sites via photothermal conversion; meanwhile, glutathione triggers decomposition of PM to release Mn2+ to activate DNAzyme in the cytoplasm for gene regulation. In vitro and in vivo experiments show that the PM-induced temperature elevation enhances the Egr-1 mRNA cleavage activity of DNAzyme, promoting downregulation of the Egr-1 protein in tumor cells. In addition, the temperature elevation induces heat stress, achieving a synergistic tumor ablation effect.

Aucubin inhibits IL-1ß- or TNF-α-induced extracellular matrix degradation in nucleus pulposus cell through blocking the miR-140-5p/CREB1 axis.

In intervertebral disc degeneration (IDD), increased proinflammatory molecules secreted by human nucleus pulposus cells (HNPCs) could promote the expression of extracellular matrix (ECM)-degrading enzymes. IDD could be affected by both genetic and environmental factors, including microRNAs (miRNAs). Aucubin, the active ingredient of a traditional Chinese medicine herb Du Zhong, has been reported to promote osteogenic differentiation; however, the role of aucubin in IDD and the underlying mechanism remain unclear. Herein, we evaluated the effect of aucubin on TNF-α- or IL-1ß-induced ECM degradation in HNPCs. By using online tools, miR-140 was selected as a candidate miRNA that is related to TNF-α or IL-1ß signaling. Overexpression of miR-140 enhanced the effect of aucubin on ECM degradation. Moreover, cAMP responsive element binding protein 1 (CREB1), a major transcriptional factor in immune-related signaling, was a direct downstream target of miR-140. CREB1 knockdown mimicked the function of miR-140 overexpression on ECM degradation. In summary, aucubin might ameliorate IL-1ß- or TNF-α-induced ECM degradation in HNPCs through regulating miR-140/CREB1.

Bu-Shen-Huo-Xue-Fang modulates nucleus pulposus cell proliferation and extracellular matrix remodeling in intervertebral disk degeneration through miR-483 regulation of Wnt pathway.

Intervertebral disk degeneration (IDD) has been widely considered as one of the main causes for low back pain, which can cause a severe impact to human health and huge economic burden to worldwide society. IDD pathogenesis can be affected by extensive degradation of extracellular matrix (ECM) and the hyperproliferation of nucleus pulposus (NP) cells. During the IDD process, expression of the ECM degradation enzymes matrix metalloproteinase and ADAMTS increases, whereas expression of ECM synthesis-related aggrecan and COL2A1 decreases. In addition, the Wnt signaling pathway is reportedly involved in the process of IDD. Bu-Shen-Huo-Xue-Fang (BSHXF), a Chinese traditional medicine formula that contains six Chinese traditional medicinal herbs, is widely used in the treatment of IDD. Herein, we obtained the serum containing BSHXF from BSHXF-fed rat and demonstrated that the BSHXF promoted NP cell proliferation and ECM synthesis through the Wnt signaling pathway. By using DIANA online tools and luciferase reporter gene assays, we confirmed that miR-483-3p and miR-23c regulated CTNNB1 and GSK3B, respectively, through direct targeting, thereby affecting the effect of BSHXF on NP cell proliferation and ECM synthesis through the Wnt signaling pathway. Taken together, we demonstrated the function and mechanism of BSHXF in regulating NP cell proliferation and ECM remodeling through the Wnt signaling pathway during IDD.

Clinical Evidence of Chinese Massage Therapy (Tui Na) for Cervical Radiculopathy: A Systematic Review and Meta-Analysis.

Objective. The review is to assess the current evidence of Chinese massage therapy (Tui Na) for cervical radiculopathy. Methods. Seven databases were searched. Randomised controlled trials incorporating Tui Na alone or Tui Na combined with conventional treatment were enrolled. The authors in pairs independently assessed the risk of bias and extracted the data. Results. Five studies involving 448 patients were included. The pooled analysis from the 3 trials indicated that Tui Na alone showed a significant lowering immediate effects on pain score (SMD = -0.58; 95% CI: -0.96 to -0.21; Z = 3.08, P = 0.002) with moderate heterogeneity compared to cervical traction. The meta-analysis from 2 trials revealed significant immediate effects of Tui Na plus cervical traction in improving pain score (MD = -1.73; 95% CI: -2.01 to -1.44; Z = 11.98, P < 0.00001) with no heterogeneity compared to cervical traction alone. No adverse effect was reported. There was very low quality or low quality evidence to support the results. Conclusions. Tui Na alone or Tui Na plus cervical traction may be helpful to cervical radiculopathy patients, but supportive evidence seems generally weak. Future clinical studies with low risk of bias and adequate follow-up design are recommended.

[Clinical effects of rehabilitation exercise in the treatment of knee osteoarthritis based on the theory of "treating muscle for bone"].

OBJECTIVE: To study the efficacy and safety of voluntary rehabilitation exercise in the treatment of knee osteoarthritis, based on the traditional Chinese medicine theory of "treating muscle for bone". METHODS: Ninety participants with early knee osteoarthritis were randomly divided into experimental group (n=45) and control group (n=45). Patients in experimental group were treated with voluntary rehabilitation exercise combined with isometric extension of quadriceps femoris. Patients in control group were treated with apparatus training combined with isometric extension of quadriceps femoris. The treatment course lasted for two weeks. Visual analogue scale (VAS), Lysholm score and total therapeutic effect were evaluated before and after treatments. RESULTS: After two weeks of treatment, cure-remarkable-effective rate in experimental group (86.67%) was higher than that in control group (71.11%). The VAS scores and Lysholm scores were significantly improved in both two groups (P<0.05). The results were significantly better in experimental group those in control group (P<0.05). There were no serious adverse events. CONCLUSIONS: Voluntary rehabilitation exercise combined with isometric extension of quadriceps femoris was effective and safe in the treatment of early knee osteoarthritis.

[Preliminary study of intervention in effect of Bushen Huoxue recipe on calcification of lumbar vertebra cartilage endplate of the aging gerbils].

OBJECTIVE: To study the effect of Bushen Huoxue decoction on calcification of cartilage endplate in lumbar vertebrae. METHODS: Six healthy male gerbils with 2-month-old were selected as normal control group, and 24 7-month-old healthy male gerbils were fed to 12-month-old to establish the aged gerbil model. Thirty gerbils were randomly divided into five groups as follow: the normal control group (n=6), model group (n=6, normal saline 4 ml/kg, intragastric 30 d), Bushen Huoxue low dose group(n=6, 1.9× 10⁻ ³ ml/g given Bushen Huoxue recipe orally, 30 d), Bushen Huoxue middle dose group(n=6, 3.8× 10⁻ ³ ml/g given Bushen Huoxue recipe orally, 30 d), Bushen Huoxue high dose group(n=6, 7.6× 10⁻ ³ ml/g given Bushen Huoxue recipe orally, 30 d), the intervention group administered for 1.36 g from 7-month-old age, 30 d. The animals were sacrificed at the age of 2 months in the normal control group and 12 months of age in the other groups. The morphology of the lumbar vertebral cartilage endplate, the area of vascular bud, the ratio of non-calcified/calcified layer were analysis by HE chromosome visual method. The expression of type X collagen and BMPs in cartilage endplates were detected by rabbit monoclonal immunohistochemical staining. RESULTS: The relative area of the vascular buds cartilage endplate measurements showed that compared with the model group, middle dose group and normal control group increased (P<0.05), high and low dose groups all had different degrees of increase, but no statistical significance(P>0.05). The ratio of cartilage endplate thickness of non-calcified/calcified showed that compared with the model group, Bushen Huoxue middle dose, normal control group increased, with statistical significance(P<0.05), and high and low dose groups all had different degrees of increase, but there were no statistical significance(P>0.05). Compared with the model group, the expression of type X collagen in the cartilage endplate of the normal group, the Bushen Huoxue low, middle and high dose groups decreased, and had statistical significance(P<0.01); compared with the model group, the expression of BMPs in the normal group, Bushen Huoxue middle dose group increased, with statistically significant(P<0.01), while the high and low dose groups increased in different degrees, but there was no statistical significance(P>0.05). CONCLUSIONS: Bushen Huoxue prescription can delay the calcification of cartilage endplate in the process of aging, suggesting that it can be used as a preventive medicine for early disc degeneration.

[Research on the stability of teaching robots of rotation-traction manipulation].

OBJECTIVE: To evaluate the stability of teaching robot of rotation-traction manipulation. METHODS: Operators were required to get the hang of rotation-traction manipulation and had clinical experience for over 5 years. The examination and data processing of the ten operators in our research were collected by the teaching robot of rotation-traction manipulation. Traction, pulling force, maximum force, pulling time, rotational amplitude and pitch range were recorded and compared for five times(G1, G2, G3, G4 and G5). The qualification rates were analyzed to evaluate the stability of teaching robot of rotation-traction manipulation. RESULTS: Nonconforming items were found in G1 and G2, for instance, pulling force(P=0.074), maximum force(P=0.264) and rotational amplitude (P=0.531). There was no statistically difference. None nonconforming item was found in G3, G4 and G5. All data were processed by SPSS and One-way ANOVA was used to analysis. Pulling force was found statistically different in G1, compared with G4 and G5(P=0.015, P=0.006). Maximum force was found statistically different in G1, compared with G4 and G5 (P=0.021, P=0.012). None differences were found in other comparisons (P>0.05). CONCLUSIONS: The teaching robot of rotation-traction manipulation used in our research could provide objective and quantitative indices and was considered to be an effective tool of assessing the rotation-traction manipulation.

Tanreqing injection for acute bronchitis disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Acute bronchitis (AB) is one of the common diseases. Tanreqing injection (TRQ) was widely used to treat patients with acute bronchitis, and many randomized controlled trials have been conducted to investigate its efficacy. OBJECTIVE: The purpose of this systematic review is to evaluate the efficacy and safety of TRQ for AB. METHODS: Eight English and Chinese electronic databases, up to October 2014, were searched to identify randomized controlled trials on TRQ for AB. Two reviewers independently extracted data and assessed the quality of each trial by using Cochrane handbook. Meta-analysis was carried out by using Review Manager software. RESULT: A total of 49 trials with 5131 participants were collected. Data of three main outcomes were pooled and analyzed as following: (1) effective rates: TRQ versus antibiotics (RR 1.12; 95% CI 1.05, 1.18; P=0.0002); TRQ plus antiviral drugs versus antiviral drugs (RR: 5.12; 95% CI 3.03, 8.66; P<0.00001); TRQ plus antibiotics versus antibiotics (RR 3.46; 95% CI 2.59, 4.62; P<0.00001); TRQ versus antibiotics plus antiviral drugs (RR 2.03; 95% CI 1.10, 3.74; P=0.02); TRQ plus conventional therapy versus conventional therapy alone (RR 1.21; 95% CI 1.15, 1.27; P<0.00001). (2) Time for fever resolution: TRQ plus antiviral drugs versus antiviral drugs (MD: -1.08; 95% CI -1.59, -0.57; P<0.00001); TRQ plus antibiotics versus antibiotics (MD -1.33; 95% CI -1.81, -0.86; P<0.00001); TRQ versus antibiotics plus antiviral drugs (MD -0.88; 95% CI -1.25, -0.51; P<0.00001); TRQ plus conventional therapy versus conventional therapy alone (MD -1.06; 95% CI -1.13, -0.98; P<0.00001). (3) Resolution of cough: TRQ plus antiviral drugs versus antiviral drugs (MD: -2.09; 95% CI -3.11, -1.43; P<0.00001); TRQ plus antibiotics versus antibiotics (MD: -2.65; 95% CI -2.88, -2.42; P<0.00001); TRQ plus conventional therapy versus conventional therapy alone (MD -1.84; 95% CI -2.85, -0.83; P=0.0003). Four trials described the adverse drug reactions of TRQ, while no severe adverse drug reactions reported. CONCLUSIONS: As a therapy for AB, TRQ has potentially beneficial effect in improving effective rates, reducing the time to resolution of fever, cough, crackles and absorption of shadows on X-ray. However, due to the limitations of methodological quality of the included trials, it is difficult to make a conclusive recommendation about TRQ treating patients with AB. Further rigorous clinical trials are warranted to evaluate the efficacy and safety of TRQ.

What caused the changes in the usage of Atractylodis Macrocephalae Rhizoma from ancient to current times?

Ancient Chinese medicine treatises on Atractylodis Macrocephalae Rhizoma (AMR), the rhizome of Atractylodes macrocephala Koidz, indicated that it possessed an expectorant effect. However, in modern times, it is commonly used as a tocolytic agent. In this study, the components of AMR that are responsible for its expectorant and tocolytic effects were evaluated in order to clarify the differences in its application between ancient and modern times. A decoction of AMR was separated into five fractions, namely, volatile oil (VO), petroleum ether (PE), alcohol eluate from macroporous resin (AE), water eluate from macroporous resin (WE), and polysaccharides (PS), using various separation methods. The expectorant experiment indicated that the VO fraction, which mainly contains atractylone, produced an obvious expectorant effect. The experiment that assessed the irritability of uterine smooth muscle (USM) showed that the PE, which is mainly composed of atractylenolides, and the PS, which is mainly composed of inulin-type polysaccharides, were the active fractions for tocolysis, but the VO fraction had the opposite action. These data suggested that volatile oils are the key components responsible for the usage change of AMR in both ancient and current usage.

Effectiveness and Safety of Manufactured Chinese Herbal Formula for Knee Osteoarthritis: Insights from a Systematic Review.

Objective. To assess the current clinical evidence of manufactured Chinese herbal formulae (MCHF) for knee osteoarthritis (KOA). Methods. Seven databases were searched from inception to May 2015. Eligible randomized controlled trials investigating the effectiveness of MCHF for KOA were included. Data extraction, methodological assessment, and meta-analyses were conducted according to the Cochrane standards. Results. A total of 17 kinds of MCHF were identified from the twenty-six included trials. Meta-analyses showed that MCHF significantly relieved the global pain of knee joints, either used alone or combined with routine treatments. Additionally, MCHF plus routine treatments significantly decreased the scores of WOMAC and Lequesne index. However, there were no statistical differences between MCHF group and routine treatment group in walk-related pain and WOMAC scores. No significant differences were found in Lysholm scores. There were twenty-one trials that mentioned adverse events. A pooled analysis showed that adverse events occurred more frequently in control group compared with MCHF group. Conclusions. Our results indicated that MCHF showed some potential benefits for KOA. However, we still cannot draw firm conclusions due to the poor methodological quality of included trials. More high-quality RCTs would help to confirm the evidence.

[Effects of serum enatninine Gumibao (Chinese character: see text) on the aroliferation and differentiation of osteoblast induced by dexamethasone].

OBJECTIVE: To investigate the effects of serum containing Gumibao (Chinese character: see text) on the proliferation and differentiation of osteoblast induced by dexamethasone. METHODS: Osteoblasts were extracted from skulls in newly born (within 24 hours) SD rats, and digested with collagenase. The first passage of cells were used for experiments. Cells were cultured in the medium containing different concentrations of dexamethasone (0, 10(-8), 10(-7), 10(-6), 10(-5) ,10(-4) mol/L). Alkaline phosphatase staining were carried out after 1 week and numbers of mineralized nodes with alizarin red staining were observed after 3 weeks. Accordingly, following the treatment of 10(-5) mol/L dexamethasone for 1 week, cells were cultured in the medium with serum containing Gumibao (Chinese character: see text). One week after Cumibao (Chinese character: see text) treatment, cells were stained with Alkaline phosphatase and collagen I and PCNA were examined by Western-blot. However, the observation of numbers of mineralized nodes with alizarin red stain required one more week. RESULTS: High concentration of dexamethasone could inhibit the expression of PCNA, collagen I, alkaline phosphatase and reduce the number of mineralized nodes of osteoblast, while serum containing Gumibao (Chinese character: see text) could reverse the inhibition. CONCLUSION: High concentration of dexamethasone could inhibit the proliferation and differentiation of osteoblastic cells, while serum containing Gumibao (Chinese character: see text) could reverse the inhibition.

[Effect of Jingang Jiangu pill (see text) on expression of integrin beta1 and alphavbeta3 in ovariectomized osteoporosis model rats].

OBJECTIVE: To investigate the regulatory effect of Jingang Jiangu pill (see text, JGJG) on expression of integrin in ovariectomized rats. METHODS: Fifty ovariectomized 10 months old female rats were randomly divided into 5 groups: Fushanmei group (FSM), Jingang Jiangu pill (see text) group (JGJG), Gusongbao granule group (GSB), Model group (OVX), Sham group. After ovariectomized,the rats were raised in the same environment for 13 weeks. The rats in JGJG group took 0.13 g JGJG pill orally each day for each rat; the rats in GSB group took 0.86 g GSB granule orally each day for each rat; the rats in FSM group took 0.28 mg FSM orally each day for each rat; and the rats in OVX and sham groups took sodium. The treatment duration of rats in above 5 groups was 13 weeks. Bone mineral density (BMD) and the expression of integrin beta1 and alphavbeta3 were detected in each group after the treatment. RESYKTS: The BMD and the expression of integrin beta1 in FSM group, JGJG group and GSB group improved obviously than that of OVX group. There were statistical difference between these groups (P<0.05). The expression of integrin alphavbeta3 of the three treating groups significantly depressed. CONCLUSION: The JGJG pill improves BMD and express of integrin beta1, in ovariectomized rats and reduces express of integrin alphavbeta3 through the regulation of the coupling of osteoblasts and osteoclasts.