Xue-Jun Cui

Prolonged upright posture induces degenerative changes in intervertebral discs in rat lumbar spine.

Study Design. Both forelimbs of rats were amputated, and these rats were kept in the custom-made cages that kept the rats in prolonged upright posture. Pathologic changes were observed in the lumbar spine at different time points after the surgery. Objective. To investigate the effect of upright posture on intervertebral discs of rat lumbar spine. Summary of Background Data. Previous studies have shown that increased axial forces on the spine can decrease the height of the intervertebral disc, but there are no data to indicate whether or not long-term and repeated assumption of the upright posture could result in degenerative changes. Methods. The forelimbs of 30 rats were amputated when they were 1-month old. These rats were kept in the custom-made cages and were forced to stand upright on their hind-limbs and tails to obtain water and food. Normal rats of the same ages kept in regular cages were used as control. The rats were killed at 5, 7, and 9 months after the surgery, and the intervertebral discs samples of lumbar spine were harvested for histologic and immunohistochemical studies. Total RNA isolated from these samples was used for real-time PCR of type II collagen (Col2&agr;1), type X collagen (Col10&agr;1), matrix metalloproteinase-13 (MMP-13), aggrecan, and disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5). Results. Histologic analysis showed degenerative changes of the intervertebral discs after surgery such as disordered collagen structure of endplate cartilage, fragmentation of annulus fibrosus, and decreased height of disc. Immunostaining revealed decreased protein level of type II collagen and increased protein expression of type X collagen. Real-time PCR showed upregulated expression of MMP 13, ADAMTS-5, and Col10&agr;1 mRNA and downregulated mRNA expression of Col2&agr;1 and aggrecan. Conclusion. Long-term and repeated assumption of the upright stance accelerates disc degeneration in rats.

Chinese herbal medicine for osteoporosis: a systematic review of randomized controlled trails.

Background. Osteoporosis is a major health problem for the elderly population. Chinese herb may be beneficial to osteoporosis due to its capability. Objectives. This study was designed to evaluate the effectiveness of Chinese medicine treatment on the patients with osteoporosis. Search Methods. Randomized controlled trials were retrieved from different 9 databases. Results. This meta analysis included 12 RCTs involving 1816 patients to compare Chinese herbs with placebo or standard anti-osteoporotic therapy in the treatment of bone loss. The pooled data showed that the percent change of increased BMD in the spine is higher with Chinese herb compared to placebo (lumber spine: WMD = 0.07, 95% CI: 0.01–0.04). In the femoral, Chinese herb showed significantly higher increments of BMD compared to placebo (femoral neck: WMD = 0.06, 95% CI: −0.02–0.13). Compared to the other standard anti-osteoporotic drugs, Chinese herbs also show advantage in BMD change (lumber spine: WMD = 0.03, 95% CI: −0.01–0.08; femoral: WMD = 0.01, 95% CI: −0.01–0.02). Conclusions. Our results demonstrated that Chinese herb significantly increased lumbar spine BMD as compared to the placebo or other standard anti-osteoporotic drugs.

Is Extracorporeal Shock Wave Therapy Clinical Efficacy for Relief of Chronic, Recalcitrant Plantar Fasciitis? A Systematic Review and Meta-Analysis of Randomized Placebo or Active-Treatment Controlled Trials

OBJECTIVE To assess the efficacy of extracorporeal shockwave therapy (ESWT) and provide clinicians with an evidence base for their clinical decision making. DATA SOURCES PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Evidence-Based Medicine Reviews. STUDY SELECTION All randomized or quasi-randomized controlled trials of ESWT for chronic recalcitrant plantar fasciitis were searched. Searching identified 108 potentially relevant articles; of these, 7 studies with 550 participants met inclusion criteria. DATA EXTRACTION Number of patients, population, body mass index, duration of symptoms, adverse effects, blinding method, and details of shockwave therapy were extracted. DATA SYNTHESIS For intervention success rate, ESWT of low intensity was more effective than control treatment of low intensity. For pain relief, the pooled data showed a significant difference between the ESWT and control groups. For function, only low-intensity ESWT was significantly superior over the control treatment. CONCLUSIONS The efficacy of low-intensity ESWT is worthy of recognition. The short-term pain relief and functional outcomes of this treatment are satisfactory. However, owing to the lack of a long-term follow-up, its long-term efficacy remains unknown.

A continuous observation of the degenerative process in the intervertebral disc of Smad3 gene knock-out mice.

Study Design. Pathologic changes were observed in the spine of small mother against decapentaplegic (Smad) 3−/− mice at different time points. Objective. To observe the degeneration of the intervertebral disc (IVD) in Smad3 gene knock-out mice with growth. Summary of Background Data. Smad3 gene knock-out (Smad3−/−) mice displays phenotypes similar to human osteoarthritis. Despite the similarities between IVD cartilage endplate and the articular cartilage, there has been relatively little interest in exploring the possibility that IVD degeneration might be driven by the deficiency of Smad3. Methods. The Smad3−/− mice were killed at the 10th, 30th, and 60th day after their birth and the IVD samples of spine were harvested for histologic and immunohistochemical studies. Total RNA isolated from these samples were used for real-time PCR analysis of type II collagen (Col2&agr;1), type X collagen (Col10&agr;1), aggrecan, and transforming growth factor-&bgr;1 (TGF-&bgr;1). Results. Compared with the wild-type mice, Smad3−/− mice appeared significantly smaller in size. Radiograph showed that the spine of Smad3−/− mice is malformation and kyphosis. Histologic analysis revealed the declined height of cartilage endplate, decreased proteoglycan and collagen content in disc of Smad3−/− mice. With growth, especially of the 30- and 60-day old Smad3−/− mice, the protein positive staining of type II collagen, aggrecan, and TGF-&bgr;1 in the disc decreased, while that of type X collagen increased. And the analysis of real-time PCR showed that the mRNA expression of Col2&agr;1, aggrecan, and TGF-&bgr;1 decreased, while that of Col10&agr;1 increased. Conclusion. Smad3 gene knock-out mice develop IVD degeneration with growth.

Leg amputation accelerates senescence of rat lumbar intervertebral discs.

Study Design. Several senescence biomarkers were observed to investigate cell senescence in degenerative intervertebral lumbar discs of foreleg-amputated rats. Objective. To determine if cell senescence is accelerated in degenerative intervertebral lumbar disc cells in an upright-rat model. Summary of Background Data. Cellular senescence was accelerated in human and sand rat degenerative intervertebral disc (IVD) cells. Repeated use of upright posture by rats contributed to degenerative disc changes. No convincing evidence of cell senescence was observed in the lumbar disc of the foreleg amputated rat. Methods. The forelimbs of 20 rats were amputated at 1 month of age such that they maintained an upright stance; rats were housed in custom-made cages. Nonamputated rats, also 1 month of age, were kept in regular cages and served as a control group. The lumbar IVDs were harvested from rats in 2 groups, at 5 or 9 months following amputation. Senescence-associated-&bgr;-galactosidase-positive staining was used to detect cell senescence. p16INK4a and p27KIP were assessed by immunohistochemistry analysis. Total RNA isolated from these samples was used to measure the gene expression of p16INK4a, RB, cyclin D1, CDK4, PTEN, p27KIP, p19ARF, p21, TERT, and RAGE by real-time polymerase chain reaction assay. Results. The highest levels of SA-&bgr;-GAL activity were detected in 9-month amputated rats. Quantitative immunohistochemical analysis showed that there were highest rates of p16INK4a and p27KIP protein expression in the cartilage endplate and anulus fibrosus of 9-month amputated rats. The mRNA levels of p16INK4a, RB, PTEN, p27KIP, p19ARF, and RAGE were upregulated. The increased cyclin D1 mRNA level was statistically significant only at the ninth month following amputation; CDK4 and TERT mRNA levels were downregulated to a similar extent at both points compared with nonamputated controls. mRNA expression of p21 was significantly downregulated. Conclusion. Accelerated cell senescence was associated with forelimb amputation that causes abnormal loading in rat lumbar IVDs.

A Systematic Review of Cross-cultural Adaptation of the Oswestry Disability Index.

Study Design. Systematic review of cross-cultural adaptation of the Oswestry Disability Index (ODI). Objective. The aim of this study was to evaluate the translation procedures for and measurement properties of cross-cultural adaptations of the ODI. Summary of Background Data. The ODI is the most commonly used questionnaire to determine the outcome of low back pain, and has been translated into many other languages, such as Danish, Greek, and Korean, and adapted for use in different countries. Methods. PubMed, the Cochrane Library, Medline, and EMBASE were searched from the time they were established to January 2015. Studies related to cross-cultural adaptation of the ODI in a specific language/culture were included. Guidelines for the Process of Cross-Cultural Adaptation of Self-Report Measures and Quality Criteria for Psychometric Properties of Health Status Questionnaire were used for assessment. Results. This study included 27 versions of ODI adaptations in 24 different languages/cultures. Only the Danish-Danish adaptation employed all six of the cross-cultural adaptation processes. Expert committee review (three of 27), back translation (eight of 27), and pretesting (nine of 27) were conducted in very few studies. The Polish-Polish (two) adaptation reported all (nine of nine) the measurement properties, whereas the Traditional Chinese-Taiwan and Hungarian-Hungarian adaptations reported six of them. Content validity (16/27), construct validity (17/27), and reliability (22/27) were determined in a relatively high number of studies, whereas agreement (three of 27), responsiveness (12/27), floor and ceiling effects (six of 27), and interpretability (one of 27) were only determined in some studies. Conclusion. We recommend the Traditional Chinese-Taiwan, Simplified Chinese-Mandarin Chinese, Danish-Danish, German-Swiss, Hungarian-Hungarian, Italian-Italian, and Polish-Polish (two) versions for application, but Traditional Chinese-Hong Kong, French-Swiss, Japanese-Japanese (two), Polish-Polish (two), Tamil-Indian, and Thai-Thai versions may need more research. Furthermore, supplementary tests for the adaptations are necessary, especially for assessing agreement, responsiveness, and interpretability. Level of Evidence: 1

Biomechanical Characteristics of Osteoporotic Fracture Healing in Ovariectomized Rats: A Systematic Review.

Biomechanical tests are widely used in animal studies on osteoporotic fracture healing. However, the biomechanical recovery process is still unknown, leading to difficulty in choosing time points for biomechanical tests and in correctly assessing osteoporotic fracture healing. To determine the biomechanical recovery process during osteoporotic fracture healing, studies on osteoporotic femur fracture healing with biomechanical tests in ovariectomized rat (OVX) models were collected from PUBMED, EMBASE, and Chinese databases. Quadratic curves of fracture healing time and maximum load were fitted with data from the analyzed studies. In the fitted curve for normal fractures, the predicted maximum load was 145.56 N, and the fracture healing time was 88.0 d. In the fitted curve for osteoporotic fractures, the predicted maximum load was 122.30 N, and the fracture healing time was 95.2 d. The maximum load of fractured femurs in OVX rats was also lower than that in sham rats at day 84 post-fracture (D84 PF). The fracture healing time was prolonged and maximum load at D84 PF decreased in OVX rats with closed fractures. The maximum load of Wister rats was higher than that of Sprague-Dawley (SD) rats, but the fracture healing time of SD and Wister rats was similar. Osteoporotic fracture healing was delayed in rats that were < = 12 weeks old when ovariectomized, and at D84 PF, the maximum load of rats < = 12 weeks old at ovariectomy was lower than that of rats >12 weeks old at ovariectomy. There was no significant difference in maximum load at D84 PF between rats with an osteoporosis modeling time <12 weeks and > = 12 weeks. In conclusion, fracture healing was delayed and biomechanical property decreased by osteoporosis. Time points around D95.2 PF should be considered for biomechanical tests of osteoporotic femur fracture healing in OVX rat models. Osteoporotic fracture healing in OVX rats was affected by the fracture type but not by the strain of the rat.

Changes of Cervical Dorsal Root Ganglia Induced by Compression Injury and Decompression Procedure: A Novel Rat Model of Cervical Radiculoneuropathy

Our study aimed to establish a model of compression injury of cervical dorsal root ganglia (DRG) in the rat and to investigate the pathological changes following compression injury and decompression procedures. Thirty rats were divided into three groups: control group receiving sham surgery, compression group undergoing surgery to place a micro-silica gel on C6 DRG, and decompression group with subsequent decompression procedure. The samples harvested from the different groups were examined with light microscopy, ultrastructural analysis, and horseradish peroxidase (HRP) retrograde tracing techniques. Apoptosis of DRG neurons was demonstrated with TUNEL staining. Changes in PGE2 and PLA2 in DRG neurons were detected with enzyme-linked immunosorbent assay (ELISA). Local expression of vascular endothelial growth factor (VEGF) was monitored with immunohistochemistry. DRG neurons in the compression group became swollen with vacuolar changes in cytoplasm. Decompression procedure partially ameliorated the resultant compression pathology. Ultrastructural examination showed a large number of swollen vacuoles, demyelinated nerve root fibers, absence of Schwann cells, and proliferation in the surrounding connective tissues in the compression group. Compared to the control group, the compression group showed a significant decrease in the number of the HRP-labeled cells and a significant increase in levels of PGE2 and PLA2, in the expression of VEGF protein, and in the number of apoptotic DRG neurons. These findings demonstrate that compression results in local inflammation, followed by increased apoptosis and upregulation of VEGF. We conclude that such a model provides a tool to study the pathogenesis and treatment of cervical radiculoneuropathy.

Chinese Herbal Medicine for Myelosuppression Induced by Chemotherapy or Radiotherapy: A Systematic Review of Randomized Controlled Trials

Background. Myelosuppression is one of the major side effects of chemo- and radiotherapy in cancer patients and there are no effective interventions to prevent it currently. Chinese herbal medicine (CHM) may be helpful due to its multidrug targets. Objectives. This study was designed to evaluate effectiveness of CHM on preventing patients from experiencing myelosuppression by chemo- or radiotherapy. Search Methods. Randomized controlled trials (RCTs) were retrieved from seven different databases from the date of database creation to April 2014. We assessed all included studies using Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 and performed statistical analysis using RevMan 5.2.1. Results. Eight RCTs were included (818 patients). Pooled data showed that increase of white blood cells (WBCs) is higher with CHM plus chemotherapy/radiotherapy than with chemotherapy/radiotherapy only. Both CHM compared to placebo and CHM combined with chemotherapy/radiotherapy compared to chemotherapy/radiotherapy lacked significant differences in the peripheral platelets, red blood cells (RBCs), and hemoglobin changes. Conclusions. Our results demonstrated that CHM significantly protected peripheral blood WBCs from a decrease caused by chemotherapy or radiotherapy. There were no significant protective effects on peripheral RBCs, hemoglobin, or platelets, which may be related to low quality and small sample of included studies.

Bone mass improved effect of icariin for postmenopausal osteoporosis in ovariectomy-induced rats: a meta-analysis and systematic review.

Objective:Ovariectomy (OVX)-induced rats are the most frequently used animal model to research postmenopausal osteoporosis. Our objective was to summarize and critically assess the bone mass improved effect of icariin (ICA) for treatment of postmenopausal osteoporosis in an OVX-induced rat model. Methods:The PUBMED, EMBASE, and Chinese databases were searched from their inception date to February 2015. Two reviewers independently selected animal studies that evaluated the bone mass improved effect of ICA compared with control in OVX-induced rats. Extracted data were analyzed by RevMan statistical software, and the methodological quality of each study was assessed. Results:Seven studies with adequate randomization were included in the systematic review. Overall, ICA seemed to significantly improve bone mass as assessed using the bone mineral density (seven studies, n = 169; weighted mean difference, 0.02; 95% CI, 0.01-0.02, I2 = 77%, P < 0.00001) using a random-effects model. There is no significant difference between ICA and estrogen (E) (six studies, n = 128; weighted mean difference, 0.00; 95% CI, −0.00 to 0.01, I2 = 54%, P = 0.01). Conclusions:Bone mass improved effect of ICA for postmenopausal osteoporosis was observed in OVX-induced rats. Assessment of the methodological quality of studies involving OVX-induced animal models is required, and good methodological quality should be valued in systematic reviews of animal studies.