Bushen Yijing Fang Reduces Fall Risk in Late Postmenopausal Women with Osteopenia: A Randomized Double-blind and Placebo-controlled Trial.

Falls in late postmenopausal women with osteopenia usually cause fractures with severe consequences. This 36-month randomized, double-blind and placebo-controlled trial with a 10-year observational follow-up study aimed to investigate the long-term effect of herbal formula Bushen Yijing Fang (BSYJF) on fall risk in the late postmenopausal women with osteopenia. 140 late postmenopausal women (Femoral neck T-score, -2.5~-2 SD) were recruited and randomized to orally receive calcium carbonate 300 mg daily with either BSYJF or placebo for 36 months. The effect was further investigated for another 10-year follow-up. During the 36-month administration, there were 12 falls in BSYJF group and 28 falls in placebo group, respectively, indicating 64% lower risk of falls (RR 0.36 [95% CI, 0.18 to 0.71]; P = 0.004) in BSYJF group. During the 10-year follow-up, 36% lower fall risk (RR 0.64 [95% CI, 0.46 to 0.89]; P = 0.009) was observed in BSYJF group. No significant difference was found in safety profile between two groups. Thirty-six-month administration of BSYJF reduced fall risk with an increase in bone mass, and its latent effect on fall risk was continually observed in the 10-year follow-up in late postmenopausal women with osteopenia. This clinical trial was registered at Chinese clinical trial registry (ChiCTR-IOR-16008942).

Bufalin Inhibits the Differentiation and Proliferation of Cancer Stem Cells Derived from Primary Osteosarcoma Cells through Mir-148a.

BACKGROUND/AIMS: Osteosarcoma (OS) is the second leading cause of cancer-related death in children and young adults. Chemoresistance is the most important cause of treatment failure in OS, largely resulting from presence of cancer stem cells (CSCs). However, CSCs isolated from cancer cell lines do not necessarily represent those from primary human tumors due to accumulation of genetic aberrations that increase with passage number. Therefore, studies on CSCs from primary OS may be more important for understanding the mechanisms driving the chemoresistance of CSCs in OS. METHODS: We established a primary culture of OS cells, known as C1OS, from freshly resected tumor tissue. We further isolated CSCs from C1OS cells (C1OS-CSCs). We analyzed the effects of bufalin, a traditional Chinese medicine, on the stemness of C1OS-CSCs. We also analyzed the microRNA (miR) targets of bufalin on the stemness of C1OS-CSCs. Moreover, we examined these findings in the OS specimen. RESULTS: Bufalin inhibited the stemness of C1OS-CSCs. Moreover, we found that miR-148a appeared to be a target of bufalin, and miR-148a further regulated DNMT1 and p27 to control the stemness of OS cells. This mechanism was further confirmed in OS specimen. CONCLUSION: Our data suggest that bufalin may be a promising treatment for OS, and its function may be conducted through regulation of miR-148a.

[Experimental research on substance P content of hypothalamus and dorsal root ganglia in rats with lumbar vertebrae Gucuofeng model].

OBJECTIVE: To detect the effects of lumbar vertebrae Gucuofeng on the substance P content of hypothalamus and dorsal root ganglia in rat models. METHODS: A hundred and twenty SPF level SD male rats with the weight of 350 to 450 g were randomly divided into rotary fixation group (RF group), simple fixation group (SF group) and sham-operation group (Sham group). The external link fixation system was implanted into the L4-L6 of rats in RF group and SF group; and in RF group, that the L5 spinous process was rotated to the right resulted in L4, L5, L6 spinous process not collinear; in SF group, the external link fixation system was simply implanted and not rotated. The rats of Sham group were not implanted the external link fixation system and only open and suture. The substance P content of hypothalamus and dorsal root ganglia were detected at 1, 4, 8, 12 weeks after operation. RESULTS: Substance P content of hypothalamus in RF group and SF group was lower than Sham group at 1, 4, 8 weeks after operation (P<0.05). Substance P content of dorsal root ganglia was higher than Sham group at 1, 4, 8, 12 weeks after operation (P<0.05). There was no significant differences in the substance P content of hypothalamus among three groups at 12 weeks after operation (P>0.05). CONCLUSION: Lumbar vertebrae Gucuofeng can inhibit the analgesic activity of substance P in hypothalamus and promote the synthesis and transmission of substance P in dorsal root ganglia, so as to cause or aggravate the pain.

Glucan HBP-A increase type II collagen expression of chondrocytes in vitro and tissue engineered cartilage in vivo.

OBJECTIVE: Although chondroprotective activities have been documented for polysaccharides, the potential target of different polysaccharide may differ. The study was aimed to explore the effect of glucan HBP-A in chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs in vivo, especially on the expression of type II collagen. METHODS: Chondrocytes isolated from rabbit articular cartilage were cultured and verified by immunocytochemical staining of type II collagen. Chondrocyte viability was assessed after being treated with HBP-A in different concentrations. Morphological status of chondrocytes-alginate hydrogel constructs in vitro was observed by scanning electron microscope (SEM). The constructs were treated with HBP-A and then injected to nude mice subcutaneously. Six weeks after transplantation, the specimens were observed through transmission electron microscopy (TEM). The mRNA expressions of disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTs-5), aggrecan and type II collagen in both monolayer culture and constructs were determined by real time polymerase chain reaction (PCR). The expression of type II collagen and matrix metalloproteinases-3 (MMP-3) in chondrocyte monolayer culture was also tested through Western blot and enzyme linked immunosorbent assay (ELISA), respectively. RESULTS: MMP-3 secretion and ADAMTs-5 mRNA expression in vitro were inhibited by HBP-A at 0.3 mg/mL concentration. In morphological study, there were significant appearance of collagen in those constructs treated by HBP-A. Accordingly, in both chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs, the expression of type II collagen was increased significantly in HBP-A group when compared with control group (P<0.001). CONCLUSIONS: The study documented that the potential pharmacological target of glucan HBP-A in chondrocytes monolayer culture and tissue engineered cartilage in vivo may be concerned with the inhibition of catabolic enzymes MMP-3, ADAMTs-5, and increasing of type II collagen expression.

[Study on the correlation between "Gucuofeng and Jinchucao" and cervical spondylosis].

OBJECTIVE: To explore the relation between "Gucuofeng and Jinchucao" and cervical spondylosis. METHODS: From March 2006 to October 2011,333 patients with cervical spondylosis were collected in the study as cervical spondylosis group; 30 subjects of control group come from student of Shuguang Hospital and other health volunteer. There were 119 males and 214 females with a mean age of (48.11 +/- 12.21) years in cervical spondylosis group and there were 6 males and 24 females with a mean age of (45.27 +/- 10.12) years in control group. In aspect of the symptom and sign, dynamic palpation, X-ray examination wer performed to find the incidence rate of "Gucuofeng and Jinchucao" in two groups. RESULTS: There was significant difference in symptom and sign, dynamic palpation, X-ray examination between two groups (P<0.01). In cervical spondylosis group, "Gucuofeng and Jinchucao" occurred in 293 cases (87.99%),there was significant difference compared with control group (P<0.01). CONCLUSION: Cervical "Gucuofeng and Jinchucao" is one of pathological point of cervical spondylosis,and it can provide a guidance for the diagnosis and treatment of cervical spondylosis.

[Clinical application of non-collinear spinous process in the diagnosis of cervical vertebra "Gu Cuo Feng and Jin Chu Cao"].

OBJECTIVE: To analyze value of X-ray in diagnosis of cervical vertebral rotation. METHODS: From May 2010 to June 2011,129 patients with cervical spondylosis were collected and examined by X-ray. Among them, 119 cases were collinear spinous, other 10 cases were excluded with collinear. Of involved patients, 28 cases were male,91 cases were females with an average age of (48.53 +/- 14.32) (ranged, 24 to 65) years. The segments and numbers of vertebral body spinous process which were not centered were recorded, and then CT scan was performed to examine segments of vertebral body and spinous process which were not centered to observe rotation of cervical vertebra and spinous process deviation. The relationship between numbers of spinous not centered and vertebral rotation was statistical analyzed. RESULTS: When the number of spinous not centered ranged from 1 to 6, vertebral rotation rate were 45.45%, 46.67%, 56.86%, 62.07%, 77.14%, 85.19% respectively. CONCLUSION: The more numbers of vertebral spinous process not centered, the more chance of corresponding vertebral rotation.

Individually integrated traditional Chinese medicine approach in the management of knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Knee osteoarthritis (OA) is considered a major public health issue causing chronic disability worldwide with the increasing number of aging people. In China and increasingly worldwide, many sufferers with knee OA are using complementary and alternative medicine including herbal drug, herbal patch, acupuncture and Tuina etc., to alleviate their symptoms. However, evidence gathered from systematic reviews or randomized controlled trials (RCT) has only validated acupuncture for the management of osteoarthritic pain. Moreover, such Traditional Chinese Medicine (TCM) methods above are commonly used in an integrative way. This trial is aimed to compare the efficacy of an individually integrated TCM approach in the management of knee OA with other single treatments as parallel randomized controls. METHODS/DESIGN: Five teaching hospitals will participate in this randomized controlled trial. 500 participants, 100 in each hospital, will be randomly assigned to receive oral administration of a Chinese herbal drug (counter osteophytes capsule), topical use of a Chinese herbal patch (Fufnag Zijin patch), acupuncture, Tuina and the individually integrated TCM approach. The individually integrated TCM approach consists of basic treatment of oral counter osteophytes capsule, variable use of Tuina, acupuncture and a herbal patch based on the severity of the patient's symptoms. The interventions are given for a period of 4 weeks. The primary outcome measure is the self-reported total score using the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcome measures include patient and investigator global assessment of response to treatment, patient and investigator global assessment of OA condition, WOMAC pain, stiffness, and physical function subscales, short-form 36 (SF-36) and TCM assessment of OA condition measured by syndromes questionnaire. Mixed models and sensitivity analysis will be used for the statistical analysis. DISCUSSION: The trial is designed to test the hypothesis that an individually integrated TCM approach is more effective than four treatment modalities used separately. The major limitation of this study is lack of placebo control and of double blinding. TRIAL REGISTRATION: Chinese Cochrane Center ChiCTR-TRC-00000176.

[Systematic review of clinical randomized controlled trials on manipulative treatment of lumbar disc herniation].

OBJECTIVE: To evaluate the efficacy and safety of the manipulative treatment on lumbar disc herniation and analyze the current status of clinical studies. METHODS: The PubMed, OVID, Cochrane Library, CBM - disc database, CNKI database and VIP Database were retrieved, and 832 literatures on manipulative treatment for lumbar disc herniation were collected, in which 8 articles met the inclusion criteria. Cochrane systematic review was used to evaluate the quality; and RevMan 4.2 was used for Meta Analysis of Literatures. RESULTS: There were total 911 patients in the 8 articles. The summary OR for the combined cure rate of the 8 articles was 3.65, and the 95% CI was [2.15, 6.20]. The summary OR for the combined efficiency was 3.56, and the 95% CI was [2.35, 5.38]. The cure rate and effective rate of the patients in manipulative group were superior to those of patients treated with other methods such as drugs, traction, acupuncture, microwave thermotherapy (all the methods were called as "other therapies"). CONCLUSION: This study shows that manipulative treatment on lumbar disc herniation is safe, effective, and both cure rate and the effective rate is better than other therapies. But the number of documents is limited and the quality is not very high, and the conclusion is still uncertain, high-quality evidence is needed to be further validated.

[Diagnosis and treatment of intervertebral disc disease based on the theory of "Gucuofeng and Jinchucao"].

It has previously been reported that the incidence rate of intervertebral disc disease including cervical and lumbar vertebra is at the 8th position among the chronic and difficult treated diseases in China. There are great challenges on the improving diagnosis and treatment as well as reducing recrudescence of this degenerative disease. It was well known that the degeneration and bulge or herniatation of intervertebral discs are the main reasons for it, and the treatment for it always focuses on the disc recovery. However, the discrepancy of the effect and expectation indicated that there were other reasons for it. Based on the clinical knowledge of intervertebral discs disease and combined with the cognition of Traditional Chinese Medicine,we proposed that the pathogenesis of intervertebral disc disease was Gucuofeng and Jinchucao, which meant that the improper location of diapophysis and the declined of muscle strength may cause the unstable of spine, unstable spine thus aggravated the semiluxation of diapophysis.

[Epimedium-derived flavonoids prevent ovariectomy-induced osteoporosis in rats independent of its enhancement in intestinal calcium absorption].

OBJECTIVE: To test our hypothesis whether a group of flavonoids (FE) derived from herbal Epimedium exerted its prevention of estrogen-deficiency-induced osteoporosis mainly through an enhancement in intestinal calcium absorption. METHODS: Forty-five 12-month-old female Wistar rats were randomly assigned into one sham-operated group and four ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX group), OVX with FE (FE group), OVX with calcium supplement (CS group), and OVX with FE and CS. Daily oral administration of FE (10 mg x kg(-1) x (d(-1)) and/or CS (56 mg x kg(-1) x d(-1)) started on day 4 after OVX for 12 weeks. Before sacrificing the animals, urine and serum samples were collected for assaying indicators for intestinal calcium absorption, regulator of calcium homeostasis and markers for bone turnover. Then, the left proximal femur was dissected for the primary-end-point index (failure force), and the second-end-point indexes (pQCT-calculated densitometry, geometry and micro-CT-quantified 3-D trabecula microarchitecture), as well as pQCT-defined cross-sectional envelope. RESULTS: FE prevented OVX-induced deterioration in failure force as well as the second-end-point indexes with no increase in uterus weight. CS had no prevention effect on OVX-induced reduction in failure force. Two-way factorial interaction analysis between FE and CS showed that the un-enhanced suppression of parathyroid hormone for calcium homeostasis provided no link between the enhanced intestinal calcium absorption and the enhanced inhibition of bone resorption in the present study. Furthermore, discrepancy between the enhanced intestinal calcium absorption and the un-enhanced primary / second-end-point indexes as well as anabolic effect was also found by the interaction analysis. CONCLUSION: Independent of intestinal calcium absorption, FE inhibited bone resorption, stimulated bone formation and accordingly prevented osteoporosis without hyperplastic effect on uterus in the OVX rat model.

Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trial.

UNLABELLED: Epimedium brevicornum maxim, a nonleguminous medicinal plant, has been found to be rich in phytoestrogen flavonoids. Results from a 24-month randomized double-blind placebo-controlled clinical trial showed that Epimedium-derived phytoestrogen flavonoids were able to exert beneficial effects on preventing bone loss in late postmenopausal women, without resulting in a detectable hyperplasia effect on the endometrium. INTRODUCTION: We performed a 24-mo randomized double-blind placebo-controlled clinical trial for evaluating the effect of the Epimedium-derived phytoestrogen flavonoids (EPFs) on BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness in postmenopausal women. MATERIALS AND METHODS: One hundred healthy late postmenopausal women, with a natural menopausal history within 10 approximately 18 yr and with a BMD T-score at the lumbar spine between -2 and -2.5 SD, were randomized into EPF treatment group (n = 50; a daily dose of 60 mg Icariin, 15 mg Daidzein, and 3 mg Genistein) or placebo control group (n = 50). All participants received 300 mg element calcium daily. BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness were measured at baseline and 12 and 24 mo after intervention. RESULTS: Eighty-five participants completed the trial. The patterns of BMD changes were significantly different between the EPF treatment group and placebo control group by repeated-measures ANOVA (p = 0.045 for interaction between time and group at femoral neck; p = 0.006 for interaction between time and group at lumbar spine). BMD was found with a decreased tendency in the placebo control group at 12 (femoral neck: -1.4%, p = 0.104; lumbar spine: -1.7%, p = 0.019) and 24 mo (femoral neck: -1.8%, p = 0.048; lumbar spine: -2.4%, p = 0.002), whereas EPF treatment maintained BMD at 12 (femoral neck: 1.1%, p = 0.285; lumbar spine:1.0%, p = 0.158) and 24 mo (femoral neck: 1.6%, p = 0.148; lumbar spine: 1.3%, p = 0.091). The difference in lumbar spine between the two groups was significant at both 12 (p = 0.044) and 24 mo (p = 0.006), whereas the difference in the femoral neck was marginal at 12 mo (p = 0.061) and significant at 24 mo (p = 0.008). Levels of bone biochemical markers did not change in the placebo control group. In contrast, EPF intervention significantly decreased levels of deoxypyrdinoline at 12 (-43%, p = 0.000) and 24 mo (-39%, p = 0.000), except for osteocalcin at 12 (5.6%, p = 0.530) and 24 mo (10.7%, p = 0.267). A significant difference in deoxypyrdinoline between the two groups was found at both 12 (p = 0.000) and 24 mo (p = 0.001). Furthermore, neither serum estradiol nor endometrial thickness was found to be changed in either groups during the clinical trial. CONCLUSIONS: EPFs exert a beneficial effect on preventing bone loss in late postmenopausal women without resulting in a detectable hyperplasia effect on the endometrium.

[Control study on analgesic effect of single-point electroacupuncture on prolapse of lumbar intervertebral disc].

OBJECTIVE: To explore an effective method for electroacupuncture treatment of pain in waist and lower extremities due to prolapse of lumbar intervertebral disc. METHODS: All 98 cases of such disease were randomly divided into a treatment group (n = 53) and a control group (n = 45). The treatment group were treated with local single-point electroacupuncture stimulation, and the control group with routine electroacupuncture stimulation for 8 sessions. The pain in waist and lower extremities in the two groups were continuously evaluated with short-form of McGill pain questionnaire (SF-MPQ). RESULTS: After first treatment, SF-MPQ scores in the two groups were significantly different from those before treatment (P < 0.001), and there were significant differences between the two groups respectively (P < 0.001) at the each time points. CONCLUSION: Local singly-point electroacupuncture has a better analgesic effect on pain in waist and lower extremities due to prolapse of lumbar intervertebral disc.

Blood-nourishing and hard-softening capsule costs less in the management of osteoarthritic knee pain: a randomized controlled trial.

The blood-nourishing and hard-softening (BNHS) capsule is a traditional Chinese formula used in the symptomatic treatment of inflammation and pain. We conducted this randomized controlled trial to compare the efficacy of BNHS with other commonly prescribed drugs. We recruited 120 patients from two teaching hospitals; 30 patients in each hospital were randomly assigned to receive BNHS. In one hospital, the 30 controls were given another traditional Chinese drug; whereas a Western medicine (chondroprotection drug/Viartril-s) was used as the control in the other hospital. Intervention was carried out over a period of 4 weeks. Primary outcome measures included self-reported pain level, and changes in stiffness and functional ability as measured by the Western Ontario McMaster Universities Osteoarthritis (WOMAC) index. Mixed models were used for statistical analysis. Substantial improvements in disease-specific symptoms were observed, after 4 weeks of treatment, in patients taking BNHS capsules. As assessed by the WOMAC index, pain level of the BNHS group decreased by 57% [95% confidence interval (CI) = 50, 63], stiffness by 63% (95% CI = 55, 71) and functional ability increased by 56% (95% CI = 50, 63). No significant differences were found in any of the outcome measures between the BNHS group and either of the comparison groups. No severe adverse effects were reported. However, this study lacked a placebo group; therefore, we conclude that BNHS appears to be as effective as commonly prescribed medicines for the relief of pain and dysfunction in knee osteoarthritis patients, but costs a lot less than other Western and herbal drugs in the study.

Phytoestrogen-rich herb formula "XLGB" prevents OVX-induced deterioration of musculoskeletal tissues at the hip in old rats.

This study investigated a phytoestrogen-rich herb formula, Xianlinggubao (XLGB) (including genistein 510 microg/g and daidzein 2500 microg/g), concerning prevention of OVX-induced deterioration of musculoskeletal tissues in 11-month-old female Wistar rats, which were randomized into Sham, OVX, and XLGB groups. Daily oral administration of XLGB (250 mg/kg/day) started after OVX for 3 months. mRNA of MHC-I IIa IIb of abductor muscle was determined by RT-PCR. The proximal femoral BMD and geometry, microarchitecture, and mechanical strength were evaluated by pQCT, micro-CT, and compressive testing, respectively. The bone turnover biochemical markers serum osteocalcin (OC) and urinary deoxypyridinoline (DPD) were evaluated. The results showed that (1) XLGB-treated OVX rats showed no difference compared to the Sham group, whereas OVX induced significant deterioration in variables related to bone density, microarchitecture, and mechanical strength (P < 0.05); (2) biochemical markers showed no difference between sham and XLGB groups as compared with higher bone turnover in OVX rats (P < 0.05); (3) mRNA expression of MHC-I IIa IIb was downregulated in OVX rats but upregulated after XLGB treatment (P < 0.05); and (4) as compared with the OVX group, no uterine hypertrophy was found in XLGB-treated rats. In conclusion, findings of this study suggested that the herbal preparation XLGB was able to prevent OVX-induced deterioration of musculoskeletal tissues at the hip without causing uterine stimulation.

[Pathogenic factors of blood circulation disturbance in lumbar intervertebral disc herniation and mechanism of Tuina manipulation in promoting circulation].

Tuina manipulation has long been used in the treatment of lumbar intervertebral disc herniation, although its therapeutic mechanisms remain uncertain. The specific characteristic syndrome of this disease is lumbocrural pain in varying degrees, which is due to mechanical compression, aseptic inflammation, blood circulation disturbance and dystrophy. These factors can act on the involved nerve roots and give rise to nerve conduction disturbance. Since the blood circulation disturbance and nerve roots dystrophy are the most important pathogenic aspects of this disease, the therapeutic effect of Tuina manipulation on lumbar intervertebral disc herniation is related to them directly or indirectly.