Establishment of a novel mouse mode of elastase-induced chronic obstructive pulmonary disease related osteoporosis / 中国骨伤

OBJECTIVE@#To establish and evaluate the model of chronic obstructive pulmonary disease (COPD) with osteoporosis induced by elastase in mice.@*METHODS@#Twenty four healthy female 8-week-old C57BL / 6 mice (weighing about 18 g) were randomly divided into three groups. The control group was given intratracheal drip of normal saline, the experimental group 1 and the experimental group 2 were given intratracheal drip of elastase, the control group and the experimental group 1 were kept for 8 weeks and then killed, the experimental group 2 was kept for 12 weeks and then killed. HE staining was used to evaluate the histopathological changes of lung and tibia in the control and experimental groups. The levels of serum inflammatory factors and broncho alveolar lavage factors (BALF) were detected by ELISA. Micro CT was used to detect the bone mass related parameters of mouse femur. The expression of osteoclastic and osteogenic genes was detected by real-time fluorescence quantitative PCR.@*RESULTS@#Lung histopathology showed that the structure of alveoli in the experimental group was disordered, the walls of alveoli became thin or broken, and the alveoli cavity expanded. IL-6 and TNF-α in BALF were significantly higher than those in control group (<0.001), while IL-1β and TNF-α in serum inflammatory factors were significantly higher than those in control group (<0.001). BV / TV(bone volume fraction), TB.Th(average bone trabecular thickness) and TB.N(average bone trabecular number) in the experimental group were significantly lower than those in the control group (<0.05), TB.Sp (average bone trabecular separation) and BS / BV (bone surface area fraction) in the experimental group were significantly higher than those in the control group (<0.01). Compared with the control group, the expression of osteoclast related marker genes increased in the experimental group (<0.05), but decreased in the experimental group(<0.05). The results of experiment 1 and experiment 2 were time-dependent.@*CONCLUSION@#In this study, elastase was used to construct a COPD model with osteoporosis successfully, which provides a suitable animal model for the future study of the pathogenesis of COPD with osteoporosis.

NSAIDs combined with radiotherapy to prevent heterotopic ossification after total hip arthroplasty / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the preventive effects and differences of NSAIDs combined with radiotherapy, NSAIDs and radiotherapy for heterotopic ossification(HO) after total hip arthroplasty(THA).</p><p><b>METHODS</b>From February 2015 to July 2016, 168 hips undergoing primary THA were divided into group A, B and C, and 163 patients were followed up (54 cases and 54 hips in group A, 55 cases and 55 hips in group B, 54 cases and 54 hips in group C). Among group A, 5 hips were primary osteoarthritis, 37 hips were secondary osteoarthritis due to avascular necrosis of the femoral head, 12 hips were secondary osteoarthritis due to acetabular dysplasia. Patients in group A received oral celecoxib (0.2 g, 2 times a day) for 2 weeks after operation. Among group B, 6 hips were primary osteoarthritis, 32 hips were secondary osteoarthritis due to avascular necrosis of the femoral head, 17 hips were secondary osteoarthritis due to acetabular dysplasia, all of which in group B were treated with preoperative single 7 Gy radiotherapy. Among group C, 5 hips were primary osteoarthritis, 35 hips were secondary osteoarthritis due to avascular necrosis of the femoral head, 14 hips were secondary osteoarthritis due to acetabular dysplasia. Patients in group C were treated with preoperative radiotherapy and celecoxib after operation. The side effects of gastrointestinal reactions were observed after operation, and the heterotopic ossification was evaluated by pelvic anterior and posterior X-ray (Brooker grading).</p><p><b>RESULTS</b>The mean clinical and radiological follow-up was 21 months(12 to 30 months). In group A, 54 hips were followed up with 7 hips with heterotopic ossification, including 5 hips of Brooker I and 2 hips of Brooker II. In group B, 55 hips were successfully followed up, with 8 hips of heterotopic ossification occurred, including 6 hips of Brooker I, 2 hips of Brooker II. In group C, 54 hips were successfully followed up, with 5 hips of heterotopic ossification occurred , including 4 hips of Brooker I, 1 hip of Brooker II. There was no significant difference in efficacy among 3 groups (²=0.743, 0.690) by chi-square test. The prevalence of side effects were as following: in group A, there were 6 hips with side effects;in group B, there were 6 hips with side effects;in group C, there were 7 hips with side effects. There was also no significant difference in side effects among 3 groups (²=0.135, 0.935).</p><p><b>CONCLUSIONS</b>The combined-therapy group has lower prevalence of HO than the NSAIDs group or radiotherapy group, but the statistical difference between them is not significant. NSAIDs is still the first choice to prevent HO after THA.</p>

Anterior cervical hybrid surgical treatment for multilevel cervical spondylotic myelopathy / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the clinical results of anterior cervical discectomy and reconstruction with a self-locking cage and internal fixation with short segmental plate for multilevel cervical spondylotic myelopathy.</p><p><b>METHODS</b>From January 2012 to June 2015, a total of 106 patients received anterior cervical discectomy and reconstruction with a self-locking cage and internal fixation with short segmental plate were followed up. There were 71 males and 35 females, aged from 42 to 74 years old with an average of(55.4±5.1) years. Three segments were involved in 82 cases and four segments in 24 cases. Operation time, blood loss, postoperative drainage, and hospitalization time were recorded. Visual analogue scale(VAS) and Japanese Orthopaedic Association Score (JOA) were analyzed before and after operation(including 5 days, 3, 6, 12 months after operation and final follow-up), and the JOA improvement rate was analyzed. The cervical lordosis and ROM were measured before and after operation(including the follow-up point above) by X-rays. The postoperative complications were recorded and analyzed as well.</p><p><b>RESULTS</b>All the operations were successful. The average operative time was (126.2±25.1) min, and the amount of blood loss was (82.1±26.3) ml. All the patients were followed up from 12 to 48 months with an average of (30.4±10.5) months. The VAS score of neck pain and JOA score was significantly better from 6.11±1.54 and 9.22±2.42 preoperatively to 2.14±0.51 and 12.46±1.42 at 5 days post-operation, respectively(<0.05). The improvement rate of JOA was (56.7±21.6)%, there was no statistically significant difference of VAS, JOA scores and the improvement rate of JOA at each time after operation (>0.05). Postoperative cervical lordosis at 3 months was significantly improved from preoperative (11.5±6.8)° to (19.6±8.9)°(<0.05), and it can keep satisfactory stability until final follow-up(>0.05). Postoperative ROM at 3 months was significantly decreased from the preoperative (37.6±10.4)° to (18.2±5.9)°(<0.05), but there was no significant change in the process of follow-up (>0.05). All the complications such as dysphagia (19 cases), axial neck pain(6 cases), cerebral fluid leakage(3 cases), and hoarseness(2 cases), got better after conservative treatment. Three cases had intervertebral space non-fusion until final follow-up(without clinical symptom), but no loosening, breakage, or displacement of internal fixation were found.</p><p><b>CONCLUSIONS</b>Anterior cervical discectomy, reconstruction with a self-locking cage and internal fixation with short segmental plate which can reduce intraoperative injury, restore cervical lordosis, improve neurological function and lower postoperative complications, it is an alternative treatment for multilevel cervical spondylotic myelopathy.</p>

Seasonal and geographical dispersal regularity of airborne pollens in China / 解放军医学杂志

Allergic diseases can be induced by abundant airborne allergenic pollens with symptoms such as allergic rhinitis and bronchial asthma,which can seriously threaten human health.The species and distribution of airborne pollens differed in different regions,based on the difference of geographical environment and climate conditions.Therefore,the occurrence of pollinosis was of obviously regional and seasonal divergence.Inappropriate urban greening,tree species selection and environmental pollution have contributed to a dramatic increase in the number of pollen sensitizing plants and hay fever.The species and dispersal regularity of allergenic pollen plants in different administrative areas in China in recent 10 years are reviewed in present paper for providing scientific basis on controlling pollinosis and reasonable greening of urban environment.

MicroRNA 181b promotes vascular smooth muscle cells proliferation through activation of PI3K and MAPK pathways.

Vascular smooth muscle cells (VSMCs) hyperplasia is a common feature of pathologic cardiovascular event such as restenosis and atherosclerosis. The role and mechanisms of microRNAs (miRs) in VSMCs proliferation are poorly understood. Here, we report that miR-181b promotes VSMCs proliferation and migration. In an animal model, miR-181b was significantly increased in the rat carotid artery after balloon catheter injury. Delivery of miR-181b inhibitor to injured artery exhibited a marked inhibition of neointimal hyperplasia. Transfection of miR-181b with "mimics" to A10 cells accelerated cell proliferation, which was accompanied by an increase of cell migration. The induction of A10 cells proliferation by miR-181b appeared to be involved in activation of S and G2/M checkpoint, concomitant with decreases in cell-cycle inhibitors p21 and p27, and increases in cell-cycle activators CDK4 and cyclinD1. In contract, miR-181b inhibition attenuated A10 cells proliferation, inhibited cell migration and arrested cell cycle transition. Moreover, forced miR-181b expression elevated the phosphorylation levels of Akt and Erk1/2, whereas inhibition of miR-181b produced the opposite effects. Additionally, inhibition of PI3K and MAPK signaling pathways with specific inhibitors, but not inhibition of JNK pathway, significantly abolished the effects of miR-181b in promoting cell proliferation. These findings demonstrate that miR-181b enhances the proliferation and migration of VSMCs through activation of PI3K and MAPK pathways.

EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion.

The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.

Relationship between fracture risk evaluated by FRAX tool and spinal curvature / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the relationship between the risk of osteoporotic fracture in old people and the spinal morphology.</p><p><b>METHODS</b>From June 2010 to January 2011, 107 old people's BMD of femoral neck were measured by Dual energy X-ray. A questionnaire survey on fracture risk factors of the 107 aged and data collection were adopted. Among the aged,41 were male and 66 were female,ranging in age from 48 to 82 years old,with an averaged of (67 +/- 6) years old. The fracture risk assessment tools (FRAX) recommended by WHO were adopted. A risk assessment on osteoporotic fracture in old people was done,followed with the calculation of the probability of the hip fracture and the main bone fractures (spine,hip,forearm or shoulder fractures) in ten years. The angles of spine vertebra, spine curvature in the upright positions of the old people were measured by using Spinalmouse. The correlation analysis along with curve fitting analysis between the probability of fracture risk and included angles of spine vertebra, spine curvature were done.</p><p><b>RESULTS</b>The probability of osteoporotic fracture had a positive relation with thoracic vertebra T7 and T8, thoracic spine curvature,lumbar curvature and incline angle in upright position (P < 0.05).</p><p><b>CONCLUSION</b>The old people's morphological characteristics of spine have the ability to reflect the risk level o osteoporotic fracture.</p>

Vinpocetine inhibits breast cancer cells growth in vitro and in vivo.

Vinpocetine is a clinically used drug for cerebrovascular disorders as well as age-related memory impairment. Of note, vinpocetine has been recently identified as a novel anti-inflammatory agent; however, its effects on cancer cells remain to be investigated. In the present study, we found that vinpocetine potently inhibited proliferation of multiple types of human breast cancer cells by arresting cell cycle at G(0)/G(1) phase. It was also revealed that vinpocetine induced cell apoptosis via mitochondria-dependent pathway. Moreover, vinpocetine impaired the migration of the strongly metastatic cell MDA-MB-231. In xenograft model of human breast cancer in nude mice, both systemic and local administration of vinpocetine significantly suppressed the tumor growth without observed toxicity. Interestingly, vinpocetine markedly attenuated the activation of Akt and signal transducer and activator of transcription factor 3 (STAT3), but had no effects on MAP kinases pathways. Collectively, the data suggest that vinpocetine possesses significant yet previously unknown antitumor properties that may be utilized for the treatment of breast cancer.

Simvastatin ameliorates angiotensin II-induced endothelial dysfunction through restoration of Rho-BH4-eNOS-NO pathway.

Endothelial dysfunction contributes to the initiation and development of hypertension. We previously found that simvastatin moderately decreases blood pressure in 2-kidney-2-clip (2k2c) renal hypertension, but the precise mechanisms are still unclear. The present study was designed to examine the protective actions of simvastatin in 2k2c-evoked endothelial dysfunction and also delineate the underlying mechanisms. Here we show that 2k2c-induced elevation in plasma angiotensin II impaired acetylcholine-induced endothelium-dependent vascular relaxation, suppressed endothelial NO synthase (eNOS) activity and reduced nitric oxide (NO) production. Additionally, the levels of tetrahydrobiopterin (BH4), an essential cofactor of eNOS, as well as the activity of GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme for BH4 synthesis, were markedly reduced. Administration of simvastatin significantly improved acetylcholine-induced endothelium-dependent carotid arteries relaxation at 9 weeks in reno-hypertensive rats. Notably, GTPCH I activity, BH4 production, p-eNOS expression and NO levels in the vascular endothelium were elevated as a result of simvastatin administration. In cultured rat arterial endothelial cells, simvastatin restored BH4, GTPCH I activity and NO release impaired by angiotensin II, and pretreatment with mevalonate (MVA) or geranylgeranyl pyrophosphate (GGPP) abolished the beneficial effects exerted by simvastatin. Moreover, RhoA inhibitor C3 exoenzyme, Rho kinase inhibitor Y-27632 and dominant negative mutant of RhoA prevented BH4 and NO loss due to Ang II treatment. Taken together, normalization of BH4-eNOS-NO pathway at least in part accounts for the beneficial actions of simvastatin on vascular endothelium during 2k2c hypertension, and RhoA-Rho kinase pathway is involved in regulation of BH4 production.

Surgical treatment and the fixator selection for Pilon fractures / 中国骨伤

<p><b>OBJECTIVE</b>To explore the internal fixation selection and the operative method of Pilon fracture.</p><p><b>METHODS</b>From Aug. 2004 to Aug. 2007,there were 40 patients with Pilon fractures involving 30 males and 10 females. Thirty cases were closed fracture and 10 were open fracture. Seven patients were treated by emergency operation, 3 patients were debrided and suture at first. Twenty-three patients were treated with open reduction and internal fixation (ORIF),the other seventeen patients were treated with LC-DCP,reconstruct plate for fixation or screw, Kirschner wire combine screw for fixation.</p><p><b>RESULTS</b>All patients were followed up for 6 to 32 months (means 19 months). The time of union of fracture was about 3 to 5 months. The outcome was evaluated according to Baired-Jackson criteria, the results were excellent in 27 cases,good in 7, fair in 5, poor in 1. Seven cases were found the operative incision and wound surface difficult to heal,among them 5 cases came from the emergency operation patients, 1 case was closed fracture patient. They were be healed by change of dressing or dermatoplasty or skin flap.</p><p><b>CONCLUSION</b>It is the key factor of treatment for Pilon fractures to correct evaluate before operation and select correct operation time. It is also important to selected suitable internal fixation and good reduction.</p>