Systematically characterized mechanism of treatment for lumbar disc herniation based on Yaobitong capsule ingredient analysis in rat plasma and its network pharmacology strategy by UPLC-MS/MS.

ETHNOPHARMACOLOGICAL RELEVANCE: Yaobitong capsule (YBTC) was a traditional Chinese medicine (TCM) and it had clinically used to treat lumbar disc degeneration (LDH) for a long time. However, the active ingredients of YBTC absorption into the plasma and its pharmacological mechanism of treatment for LDH still remained unclear. AIM OF THE STUDY: In this study, our research committed to identify the absorbed active ingredients of YBTC in rat plasma, and it may be a potential mechanism of action on LDH by the biological targets regulating related pathways. MATERIALS AND METHODS: An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to identify the absorption components and metabolites of YBTC in rat plasma, and the network pharmacology was further investigated to illuminate its potential mechanism of treatment for LDH by the biological targets regulating related pathways. RESULTS: The network analysis found that 56 components were identified as its main active ingredients including ginsenoside Rg1, ginsenoside Rb1, senkyunolide H, and tetrahydropalmatine, etc. Combining with biological process, cellular component and molecular functions of GO, and kyotoencyclopedia of genes and genomes pathway enrichment analysis to perform network topology analysis on core targets. These active ingredients regulated 29 mainly pathways by 87 direct target genes including MAPK, Ras, PI3K-Akt, and NF-kappa B signaling pathway, etc. CONCLUSION: In this study, the absorption active ingredients of YBTC in rat plasma were firstly combined with the network pharmacology investigation to elucidate its biological mechanism of treatment for LDH in vivo. It inhibited excessive inflammatory reactions, thereby reducing the sensitivity of the nerves to reduce pain and relieve LDH, and potential medicine targets could be identified to clarify the molecular mechanism of YBTCs' regulation of LDH.

Effect of subcutaneous needling on visual analogue scale, IgG and IgM in patients with lumbar disc herniation: Study protocol clinical trial (SPIRIT Compliant).

BACKGROUND: Lumbar disc herniation (LDH) is a disease commonly seen in clinical practice. In the majority of such patients presenting in clinic, the symptoms can be relieved or even abolished after non-surgical treatment. Floating needle therapy has attracted considerable attention as a promising non-surgical technique to treat LDH, as demonstrated in previous studies. The purpose of the present study was to evaluate the outcomes of patients treated using this therapy in a single blind and randomized controlled trial by recording patient report questionnaires and objective test data, and to explore the feasibility and preliminary effects of floating needle therapy for patients with LDH. METHODS: A total of 80 patients who fulfilled the inclusion criteria were randomly divided into a Fu's subcutaneous needling (FSN) group and an acupuncture group then treated in accordance with procedures appropriate for a single blind and randomized controlled trial. The FSN group received 12 FSN therapy sessions over a 3-week period, and the acupuncture group received acupuncture therapy at specified points using acupuncture needles. The principal measurements were scored using the visual analogue scale (VAS), Japanese Orthopedic Association (JOA) Score, and Oswestry disability index (ODI) before and 3 weeks after treatment. Secondary measurements included immune function IgG and IgM measurements performed at the same time and adverse reactions during treatment. RESULTS: The results of this trial will be published on the website of China Clinical Trial Registration Center (http://www.chictr.org.cn/searchprojen.aspx) and in peer-reviewed journals or academic conferences. CONCLUSIONS: This study will explore the feasibility and preliminary effects of floating needle therapy for the treatment of patients with LDH. REGISTRATION: PROSPERO (registration number ChiCTR1900024045).

Clinical effects of electrical stimulation therapy on lumbar disc herniation-induced sciatica and its influence on peripheral ROS level.

OBJECTIVE: To study the clinical effects of electrical stimulation therapy on lumbar disc herniation-induced sciatica and its influence on peripheral reactive oxygen species (ROS) level. METHODS: 100 patients with lumbar disc herniation-induced sciatica were selected, and were randomly divided into the control and research group. The control group was treated with traction and other basic therapies, while the research group was treated with electrical stimulation. The pain degrees, peripheral ROS levels and clinical effects prior to treatment and at 4 weeks after treatment were examined. RESULTS: The total cure-remarkable-effectiveness rate of patients in research group was higher than that in control group (p<0.05). Before treatment, the pain rating index (PRI), present pain intensity (PPI) and visual analogue scale (VAS) score had no statistically significant differences between the two groups. After treatment, PRI, PPI and VAS scores in the two groups were lower than those prior to treatment; these indexes in research group were lower than those in control group, and the differences were statistically significant (p<0.05). After treatment, the peripheral ROS levels in the two groups were lower than those before treatment; it was lower in research group than that in control group (p<0.05). CONCLUSION: Electrical stimulation has a significant effect in the treatment of lumbar disc herniation-induced sciatica, which can effectively reduce the pain, alleviate the clinical symptoms and signs of patients, regulate the peripheral ROS level, and prevent the oxidative damage of myocardial tissues.

Gua Sha attenuates thermal hyperalgesia and decreases proinflammatory cytokine expression in serum in rats with lumbar disc herniation induced by autologous nucleus pulposus.

OBJECTIVE: To investigate the analgesic effect of Gua Sha and its underlying mechanism in rats with noncompressive lumbar disk herniation induced by autologous nucleus pulposus. METHODS: A rat model of noncompressive lumbar disk herniation was established and rats were randomly divided into model group, sham group, and Gua Sha group (24 in each group). Gua Sha was performed from the 5th day after the surgery, once every other day, 3 times for a course of treatment, and totally 3 courses. The thermal withdrawal latency was evaluated using the intelligent hot plate one day before the surgery, and on days 4 (the day before the treatment), 10 (the end of the first course), 16 (the end of the second course) and 22 (the end of the third course). On days 4, 10, 16 and 22, six rats in each group were picked randomly and their blood samples were drawn to assess the expression of interleukin-1¦Â (IL-1¦Â), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-¦Á). RESULTS: Compared to rats in the sham group, the application of nucleus pulposus to right L5 dorsal root ganglion induced prolonged thermal hyperalgesia, and up-regulated the expression of IL-1¦Â, IL-6 and TNF-¦Á in serum (P < 0.01). The therapy of Gua Sha attenuated thermal hyperalgesia potently, inhibited the expression of IL-1¦Â, IL-6 and TNF-¦Á in a time-dependent manner (P < 0.01). There were no significant differences in the thermal withdrawal latency and the expression of inflammatory cytokines between the sham and Gua Sha groups at the end of the treatment (P > 0.01). CONCLUSION: The current study showed that Gua Sha might alleviate thermal hyperalgesia in rats with lumbar disc herniation induced by autologous nucleus pulposus via inhibiting the expression of proinflammatory cytokins.

[Effect of medicinal-cake-separated moxibustion on functional activity of back-leg and plasma substance P level in patients with lumbar disc herniation].

OBJECTIVE: To observe the effect of medicinal-cake-separated moxibustion combined with acupuncture on back-leg activities and plasma substance P (SP) levels in patients with lumbar disc herniation, so as to reveal its mechanism underlying pain relief. METHODS: A total of 114 patients with lumbar disc herniation were randomly divided into control group (n=56) and treatment group (n=58) according to a random digits table. Patients of the control group were treated by manual acupuncture stimulation of main acupoints Jiaji (EX-B 2), Huantiao (GB 30, affected side), Chengshan (BL 57, affected side), Kunlun (BL 60, affected side), and supplemented acupoints Yanglingquan (GB 34), Weizhong (BL 40) and Zusanli (ST 36) in combination with wheat-flour-cake separated moxibustion at the main acupoints, and patients of the treatment group were treated by medicinal-cake [Chuanwu (Radix Aconiti), Caowu (Radix Aconiti Kusnezoffii), Ruxiang (Olibanum), etc. ]-separated moxibustion in combination with manual acupuncture stimulation of the same acupoints mentioned above. Acupuncture treatment was conducted for 30 min, followed by moxibustion for 15 min. The treatment was given once daily for 10 days. The patients' back-leg functional activity ability was assessed using straight-leg raising test, and the pain state assessed using visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) scores, respectively. The therapeutic effect was evaluated by using "Crite- ria for Diagnosis and Outcome Evaluation of Clinical Disorders or Syndromes of Chinese Medicine" issued in 1994 and plasma SP content was detected by radioimmunoassay. RESULTS: After the therapy, the back-leg activity score and JOA score of both groups were significantly higher than those of pre-treatment in the same one group (P<0. 05, P<0. 01), and those of the treatment group were significantly higher than those of the control group (P<0.05). The VAS score of the treatment group was re- markably lower than that of the control group (P<0. 01). After the treatment, the plasma SP content was markedly lower in the treatment group than in the control group (.P<0O. 05 ) . CONCLUSION: Medicinal-cake-separated moxibustion therapy can ame- liorate pain severity and functional activity of the back-leg pain patients with lumbar disc hernia, which may be related to its effect in reducing blood SP level.

[Lumbar disc herniation treated with qi pathway intervention and spinal adjustment: a randomized controlled trial].

OBJECTIVE: To compare the efficacy difference in the treatment of lumbar disc herniation (LDH) between the comprehensive therapy of qi pathway intervention and the spinal adjustment and the conventional therapy of acupuncture and Tuina and explore the analgesic mechanism. METHODS: Seventy-one cases were randomized into a comprehensive therapy group (36 cases) and a conventional therapy group (35 cases). In the comprehensive therapy group, the acupoints in the region of abdominal qi pathway were selected and stimulated manually with both hands. In combination, the spinal adjustment therapy was applied. In the conventional therapy group, Shenshu (BL 23), Dachangshu (BL 25), Huantiao (GB 30) and Chengfu (BL 36) on the affected side were selected and stimulated with the conventional needling technique. Additionally, the routine Tuina therapy was applied. Before and after treatment, the visual analogue scale (VAS), Oswestry disability index (ODI) questionnaire, the health related quality of life (SF-36) questionnaire and the level of serum tumor necrosis factor (TNF-alpha) were adopted to determine analgesic effect and clinical efficacy. RESULTS: In the comprehensive therapy group, the curative and effective rate was 91.7% (33/36), which was apparently superior to 77.1% (27/35) in the conventional therapy group (P < 0.05). The analgesic effect in the first 10 treatments in the comprehensive therapy group was apparently superior to that in the conventional therapy group (P < 0.05). ODI after treatment was improved significantly in both groups (both P < 0.05), in which the result in the comprehensive therapy group was superior to that in the conventional therapy group (P < 0.05). After treatment, the SF-36 values of gener al health, bodily pain, physiological functioning, social functioning and emotional functioning in the comprehensive therapy group were superior to that in the conventional therapy group (all P < 0.05). After 15 treatments, the level of serum TNF-alpha in the comprehensive therapy group was lowered as compared with that before treatment and lower apparently than that in the conventional therapy group (P < 0.05); after 30 treatments, it was also lower than that in conventional therapy group (P < 0.05). CONCLUSION: In the guide of the theory of qi pathway, the comprehensive therapy of acupuncture and spinal adjustment intervention achieves the quick and good efficacy on LDH as compared with the conventional acupuncture and Tuina and improves the quality of life for the patients to certain extent. The analgesic effect of this therapy is relevant with the decrease of serum TNF-alpha.

Effect of scraping therapy on interleukin-1 in serum of rats with lumbar disc herniation.

OBJECTIVE: To explore the effect of scraping therapy on the Interleukin-1 (IL-1) levels of rats with lumbar disc herniation (LDH). METHODS: Fifty male rats were devided into a blank group (A), a sham operation group (B), a model group (C), a scraping group (D), and a drug group (E). The rats in the group B were treated with sham operation, and groups C, D and E were made into the LDH model by operation. After operation, group C were treated with no interventions, D were given scraping and E were fed with azathioprine. Then the IL-1 levels of different groups were detected by enzyme-linked immuno sorbent assay method. And the transplanted coccygeal vertebra discs were observed by pathological section. RESULTS: The IL-1 levels in the groups C, D, and E were significantly higher than those in the groups A and B (all P < 0.01), which proved the operation was successful. The IL-1 levels in the groups D and E at different periods had statistical significance (F = 414.158, P < 0.01). The treatment periods and interventions have interation (F = 46.613, P < 0.01). Multiple comparison results showed that the IL-1 levels in the groups D and E was significantly lower than that in the group C (P < 0.01), while the IL-1 levels between the groups D and E had no statistical significance (P > 0.05). Moreover, pathological section indicated that immuno-inflammatory response was hardly found in coccygeal vertebra discs in the groups A and B, while local immuno-inflammatory responses of the groups D and E were much lighter than that of the group C. CONCLUSION: Scraping therapy could inhibit the immuno-inflammatory responses in the rats with LDH caused by transplantation of autologous nucleus pulposus.

[Effects of balance-acupuncture stimulation of "back pain" and "hip pain" points on plasma beta-endorphin and ACTH contents in rats with lumbar disc herniation].

OBJECTIVE: To observe the effect of balance acupuncture on the thermal pain threshold and plasma beta-endorphin (beta-EP) and adrenocorticotrophic hormone (ACTH) levels in lumbar disc herniation rats so as to research its mechanisms underlying improvement of lumbar disc protrusion. METHODS: A total of 120 male rats were randomly divided into blank control (control) group, model group, sham-operation(sham)group, and acupuncture group (n=30) which were further divided into 7-days (d) and 14-d subgroups. Rats in the acupuncture group were treated with balance acupuncture of "Back Pain" point (the midpoint between two eyes) and "Hip Pain"point (the midpoint between the acromial process and the axillary furrow). Thermal pain threshold was detected by using radiant heat detector. Plasma beta-EP and ACTH levels were determined by radioimmunoassay. RESULTS: Compared with the control group and pre-operation and sham group, the thermal pain reaction was increased significantly in the model group (P < 0.05). In comparison with the model group, the thermal pain reaction was decreased obviously from day 10 after acupuncture treatment in the acupuncture group (P < 0.05). Compared to the control group, plasma beta-EP contents on day 7 and 14 and ACTH level on day 14 in the model group were increased significantly (P < 0.05), while in comparison with the model group, plasma beta-EP contents on day 7 and 14 and ACTH level on day 14 in the acupuncture group were down-regulated markedly (P < 0.05). No significant difference were found between the control and sham groups in plasma beta-EP contents and ACTH levels on day 7 and 14 (P > 0.05). CONCLUSION: Balance acupuncture treatment can lower plasma ACTH level in lumbar disc herniation rats, which may contribute to its effect in easing lumbar disc herniation pain in clinic practice.

[Effect of the mixed liquor of danshen and magnesium sulfate injection on IgG and IgM in serum of rabbits with lumbar intervertebral disc herniation].

OBJECTIVE: To explore the effect of the mixed liquor of danshen and magnesium sulfate injection on inflammatory reaction caused by autoimmune response of rabbits with lumbar intervertebral disc herniation. METHODS: Sixty rabbits were divided into blank group (10 rabbits), sham operation group (10 rabbits), model group (40 rabbits) according to method of random digits table. Then model group was divided into made group (group A, 10 rabbits), normal saline group (group B, 10 rabbits), aescin natrium group (group C, 10 rabbits) and danshen and magnesium sulfate injection group (group D,10 rabbits). After model success of lumbar intervertebral disc herniation, different drugs were given to rabbits with lumbar intervertebral disc herniation by ear margin vein. The rabbits of the group C,B,D were respectively given aescin natriu (0.5 mg/kg), normal saline (5 ml/kg), danshen and magnesium sulfate injection (2.0 mg/kg). The rabbits of blank group, sham operation group and group A were not given any disposal. The IgG and IgM level in serum of different groups were determined with ELISA method in fourteen day after model success and drugs given. RESULTS: The level of IgG and IgM in the group A was higher than that of blank group and sham operation group (P < 0.05). The level of IgG and IgM in the group D was lower than that of group B,C (P < 0.05). CONCLUSION: The mixed liquor of danshen () and magnesium sulfate injection could inhibit inflammatory reaction caused by autoimmune response of lumbar intervertebral disc herniation,which provides a new alternative for lumbar intervertebral disc herniation.

Reduction in high blood tumor necrosis factor-alpha levels after manipulative therapy in 2 cervicogenic headache patients.

OBJECTIVE: This case report discusses the treatment of 2 patients with cervicogenic headache (CHA) attending the Outpatient Clinic of the Hungarian National Institute for Rheumatology and Physiotherapy (Budapest, Hungary) and reviews the pathophysiology, therapeutic strategy, and problems associated with the treatment of CHA. CLINICAL FEATURES: Patient 1 was a 27-year-old female who sustained a whiplash injury. A sharp, shooting headache developed, readily induced, and aggravated by just bending the neck backward or by turning her head. Magnetic resonance imaging revealed a disk protrusion at C4-C5 pressing the anterior cerebrospinal space. Patient 2 was a 62-year-old female who sustained a whiplash injury; her cervical movements became restricted, which precipitated headaches. Magnetic resonance imaging revealed a paramedian disk hernia between the C4 and C5 vertebrae that intruded into the right ventral cerebrospinal space. INTERVENTION AND OUTCOME: After 4 weeks of manipulative therapy for patient 1, both active and passive range of motion returned to normal, and the high tumor necrosis factor-alpha (TNF-alpha) level (63 pg/mL) was substantially reduced (28 pg/mL). Patient 2 was started on manipulative therapy twice a week for 4 weeks; after 2 months, the patient became symptom-free, and high TNF-alpha level (72 pg/mL) was reduced greatly (35 pg/mL). CONCLUSION: Two patients with whiplash injury and disk herniation developed CHA associated with very high TNF-alpha levels. After manipulative therapy, these patients became symptom-free, and their TNF-alpha levels decreased substantially.

Determination of iron, copper, zinc, magnesium and selenium in plasma and erythrocytes in neurosurgical patients.

A direct method for determination of Fe, Cu, Zn, Mg and Se in erythrocytes was developed. The aim of the present study was to establish a method for examining perioperative levels of the above mentioned elements simultaneously in erythrocytes and plasma by atomic absorption spectrophotometry in 11 patients undergoing neurosurgery for acute spinal nerve compressions because of intervertebral disk prolapses. Reference values for erythrocytes were 11.49 +/- 3.48 mmol/mmol Hb; 0.82 +/- 0.087 mmol/mmol Hb; 9.01 +/- 2.20 mmol/mmol Hb; 0.104 +/- 0.032 mmol/mmol Hb; 0.07 +/- 0.050 mmol/mmol Hb for iron, copper, zinc, magnesium, and selenium, respectively. Postoperative erythrocyte concentrations did not differ significantly compared to those obtained preoperatively and remained within the reference ranges perioperatively. For plasma the following reference values were used: 19.0 +/- 8.0 mmol/l (Fe); 20.1 +/- 8.2 mmol/l (Cu); 15.4 +/- 4.6 mmol/l (Zn); 0.9 +/- 0.15 mmol/l (Mg); 1.02 +/- 0.3 mmol/l (Se). There was a significant decrease in the concentration of copper in plasma (13.41 +/- 3.46 mmol/l, p < 0.1) and zinc (10.73 +/- 2.73 mmol/l, p < 0.1) immediately postoperative, iron (10.56 +/- 3.91 mmol/l, p < 0.1) and zinc on day 1 (11.28 +/- 1.88 mmol/l, p < 0.10), and a significant postoperative increase of copper on day 5 (18.81 +/- 3.97 mmol/l, p < 0.1), postoperatively. The mean plasma concentrations of iron, copper, zinc magnesium and selenium remained within the reference ranges during the entire period.