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28 December 2017, Volume 21 Issue 36 Previous Issue    Next Issue

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Anti-osteoarthritis activity of urtica extracts at different concentrations Zheng Xiao-fen 2017, 21 (36):  5741-5746.  doi: 10.3969/j.issn.2095-4344.2017.36.001 Abstract ( 379 )   PDF (1039KB) ( 276 )   Save BACKGROUND: Urtica, as a traditional Chinese medicine, is famous for anti-inflammatory, detumescence and anti-rheumatic effects, but its effect on osteoarthritis remains unknown. OBJECTIVE: To investigate the therapeutic effect of different concentrations of urtica on osteoarthritis and the underlying mechanism. METHODS: (1) Eighteen rats were selected, and after their hair was shaved, the rats were divided into three groups (n=6 per group). The rat skin was painted with paraffin, urtica colloid and 0.8% formaldehyde, respectively, and the skin rash and swelling were observed. (2) Thirty rats were selected, and the rat model of osteoarthritis was established by injecting papain, followed by equally allotted into 100, 200, and 400 mg/kg urtica and positive control groups. The diameter of the rat left knee was measured at 1, 2 and 3 weeks after administration to determine the severity of knee swelling. The rat model of acute pain was established with 0.6% acetic acid solution, and then the model rats were subjected to different concentrations of urtica or normal saline (control group). (3) The frequency of rat tumbling and twisting was observed to determine the analgesic effect of urtica. The levels of interleukin-1β, tumor necrosis factor-α and matrix metalloproteinase 3 in the synovial fluid of the left knee joint were detected by ELISA at 1, 2 and 3 weeks after administration. RESULTS AND CONCLUSION: After urtica administration, no edema or rash appeared on the rat skin surface. Compared with the control group, 200 and 400 mg/kg urtica could reduce joint swelling and pain, showing no significant difference from indomethacin. Compared with the control group, 200 and 400 mg/kg urtica reduced the levels of interleukin-1β, tumor necrosis factor-α and matrix metalloproteinase 3 in the synovial fluid. These results manifest that urtica exerts the effects of anti-inflammation, analgesia, detumescence and anti-osteoarthritis. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Effectiveness and safety of celecoxib combined with diacerein in the treatment of senile degenerative knee osteoarthritis: study protocol for a randomized controlled trial Wang Guo-dong, Yang Ling-yun, He Bin, Wang Yun-hua, Chen Qi, Fan Lei 2017, 21 (36):  5747-5751.  doi: 10.3969/j.issn.2095-4344.2017.36.002 Abstract ( 557 )   PDF (864KB) ( 331 )   Save BACKGROUND: The non-steroidal anti-inflammatory drug celecoxib, used for the treatment of senile degenerative knee osteoarthritis, has a rapid onset of action and few side effects. However, it cannot prevent the occurrence and development of knee osteoarthritis. Celecoxib withdrawal is likely to induce a rebound increase in inflammation that may aggravate symptoms. Diacerein is a drug used to improve articular cartilage metabolism. It can delay the progression of senile degenerative knee osteoarthritis, but has a slow onset of action. Whether combined treatment with celecoxib and diacerein provides complimentary actions to achieve a better therapeutic effect on senile degenerative knee osteoarthritis remains unclear. Whether combined treatment with celecoxib and diacerein provides complimentary actions to achieve a better therapeutic effect on senile degenerative knee osteoarthritis remains unclear. OBJECTIVE: To investigate the effectiveness and safety of celecoxib combined with diacerein in the treatment of senile degenerative knee osteoarthritis. METHODS: This is a prospective, single-center, randomized controlled trial. Three hundred patients with senile degenerative knee osteoarthritis who receive treatment at the Department of Orthopedics, Second Affiliated Hospital of Nanjing Medical University, China will be randomly assigned to celecoxib (200 mg, once a day, orally), diacerein (50 mg, twice a day, orally), and celecoxib+diacerein (celecoxib 200 mg, once a day, orally and diacerein 50 mg, twice a day, orally) groups, with 100 patients in each group. Patients in each group will be treated for 12 successive weeks, and a 36-week follow-up will be performed. The primary outcome measure of this study is the 20-meter walk pain visual analogue scale score before and 1, 4, 12, 24, and 36 weeks after treatment. The secondary outcome measures of this study include osteoarthritis index and X-ray image findings of the knee before and 1, 4, 12, 24, and 36 weeks after treatment, as well as the incidence of adverse events at 1, 4, 12, 24, and 36 weeks after treatment. This study was approved by the Ethics Committee of the Second Affiliated Hospital of Nanjing Medical University, China (approval No. (2017)KY-091). The study protocol will be performed in strict accordance with the Declaration of Helsinki formulated by the World Medical Association. Written informed consent of the study protocol and procedure will be obtained from each patient. Participant recruitment will begin in January 2018. Sample and data collection will begin in January 2018 and end in December 2018. Outcome measures will be analyzed in January 2020. The trial will end in February 2020. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal. This trial was registered with the Chinese Clinical Trial Registry (registration No. ChiCTR-IOR-17013867). DISCUSSION: Results from this study will help to determine whether celecoxib and diacerein complement each other to produce a long-acting, safe, reliable, and rapid-onset analgesic effect in patients with senile degenerative knee osteoarthritis. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Effects of insulin glargine on fracture healing and osteocalcin expression in type 2 diabetic rats Zheng Bai1, Xin Bing2, Huang Dong2, Liu Yong-tao2, Liu Guo-dong1, Sun Bai-han1, Yuan Feng2, He Yu-ze2 2017, 21 (36):  5752-5756.  doi: 10.3969/j.issn.2095-4344.2017.36.003 Abstract ( 304 )   PDF (2218KB) ( 243 )   Save BACKGROUND: Insulin analogues have been extensively applied in the treatment of diabetes mellitus. Insulin glargine has a higher affinity for insulin like growth factor 1 receptor compared with human insulin. Further research is needed to ensure whether insulin and its analogues exert same effects on fracture healing in type 2 diabetes mellitus. OBJECTIVE: To observe the osteocalcin expression and callus formation in the healing of fracture in type 2 diabetic rats induced by human insulin and insulin glargine, to observe the difference between two treatment methods, and to explore the related mechanisms. METHODS: Sixty-four Sprague-Dawley rats were randomly assigned into human insulin group (group A), insulin glargine group (group B), diabetes mellitus group (group C) and control group (group D). Rats in the groups A, B and C were fed with high-sugar and high-fat diet for 4 weeks followed by intraperitoneal injection of small-dosage streptozotocin twice, to establish the rat models of type 2 diabetes mellitus. After the right tibia of each rat was broken, insulin glargine and Novolin 30R were used in the groups A and B, respectively. Fracture healing was observed on X-ray, callus formation and number of osteoblasts were observed by microscope, and serum level of osteocalcin was measured by ELISA method at 1, 2, 4, and 6 weeks after modeling. RESULTS AND CONCLUSION: X-ray results revealed better fracture healing in the groups A, B and D than the group C. Osteoblast proliferation in callus was significantly better in the groups A, B and D than in the group C. Serum level of osteocalcin in each group was on the rise, which was significantly higher in the groups A, B and D than the group C (P < 0.05), but had no significant difference among groups A, B and D (P > 0.05). In summary, insulin glargine can increase the serum level of osteocalcin, accelerate the callus formation, and improve the healing of fracture in type 2 diabetic rats. Furthermore, there is no significant difference in the therapeutic efficacy between insulin glargine and human insulin. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Role of stromal cell-derived factor 1/CXC chemokine receptor axis in rat tooth movement Cheng Qian1, Lin Fu-wei1, Xie Yi-jia1, Huang Yue1, Wang Jun2 2017, 21 (36):  5757-5762.  doi: 10.3969/j.issn.2095-4344.2017.36.004 Abstract ( 363 )   PDF (1024KB) ( 238 )   Save BACKGROUND: Orthodontic treatment has a long course and referral interval, which is an important difficulty. How to accelerate orthodontic tooth movement is an issue of concern. OBJECTIVE: To testify whether the local injection of AMD3100 (CXCR4 antagonist) can accelerate the tooth movement or not, and to explore the role of stromal cell-derived factor 1/CXC chemokine receptor axis in tooth movement. METHODS: Ninety Sprague-Dawley rats aged 8-10 weeks old were selected and the models of orthodontic tooth movement were established. The model rats were randomized into three groups, and then given the injection of stromal cell-derived factor 1, AMD3100 or PBS. The rats were killed at 1, 3, 5, 7, 10 and 14 days to measure the tooth movement distance. RESULTS AND CONCLUSION: The tooth movement distance showed difference among three groups; AMD3100 could facilitate the tooth movement, while stromal cell-derived factor 1 exerted inhibitory effect on the tooth movement. To conclude, stromal cell-derived factor 1/CXC chemokine receptor axis plays an important role in tooth movement. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Three-dimensional finite element analysis of the stress distribution on the temporomandibular joint after single maxillary extraction orthodontics in adult patients with Class II division 1 malocclusion Lv Ru-ya, Yin Yan-jiao, Liu Hai-xia, Chen Qiu-qiu, Wang Jing 2017, 21 (36):  5763-5768.  doi: 10.3969/j.issn.2095-4344.2017.36.005 Abstract ( 407 )   PDF (1158KB) ( 241 )   Save BACKGROUND: Clinical evaluation gives much attention to occlusion and improvement of soft tissue profile, while little is reported concerning the stress distribution on the temporomandibular joint in the treatment of Class II division 1 malocclusion adult patients undergoing single maxillary extraction orthodontics. OBJECTIVE: To analyze the stress distribution on the temporomandibular joint in the treatment of Class II division 1 malocclusion with single maxillary extraction orthodontics. METHODS: The three-dimensional finite element models of normal and Class II division 1 malocclusion before and after single maxillary extraction orthodontics according to CT and MRI data. The stress distribution on the temporomandibular joint was analyzed after mechanical loading and boundary constraint. RESULTS AND CONCLUSION: Compared with Class II division 1 malocclusion, the stress distribution on the temporomandibular joint after single maxillary extraction orthodontics had no significant stress concentration area, and the equivalent stress of the condyle was lower than that before treatment, and the equivalent stress of the articular disc and the glenoid fossa of temporal bone were larger than those before treatment. However, the stress was well-distributed, basically fulfilling the stress characteristics of normal occlusion. To conclude, single maxillary extraction orthodontics reduces the risk of temporomandibular joint disorder in the patients with Class II division 1 malocclusion, which is balanced and stable in line with the goal of orthodontic treatment. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Characteristics of dental arch and basal bone in permanent dentition Angle Class II malocclusion based on three-dimensional digital models  Wu Jie1, Wang Chao-ran2, Zhao Wei1, Sun Meng-jiao1, Li Hong-fa1 2017, 21 (36):  5769-5774.  doi: 10.3969/j.issn.2095-4344.2017.36.006 Abstract ( 387 )   PDF (1155KB) ( 329 )   Save BACKGROUND: An orthodontist can gain all comprehensive data about the tooth and jaw based on a model measurement. With the development of CAD/CAM, a three-dimensional (3D) digital model shows more accurate information than a traditional model. OBJECTIVE: To explore the characteristics of dental arch and basal bone in permanent dentition Angle Class II malocclusion based on 3D digital models. METHODS: Thirty cases of normal occlusionin permanent dentition were selected as control group, and 30 cases of Angel II1 and 30 cases of Angel II2 malocclusion were enrolled, respectively. Three kinds of 3D digital models were established using a 3shape R700 scanner and measured with Orthoanalyzer 2013. The data of individual normal occlusion and Angel II1 and Angel II2 data were analyzed statistically with SPSS 19.0 software respectively. Intergroup comparison was analyzed by the least significant difference test method. RESULTS AND CONCLUSION: Maxillary and mandibular dental arch length and maxillary dental arch width of front section (3-3) and middle section (4-4)/maxillary basal bone length and mandibular basal bone width of middle section (4-4): II2 > normal occlusion > II1 (P < 0.05). Mandibular dental arch front width of section (3-3)/maxillary and mandibular basal bone length: normal occlusion > II1> II2 (P < 0.05). Maxillary dental arch width of behind section (6-6)/maxillary basal bone width of front section (3-3) and middle section (4-4)/mandibular basal bone width of front section (3-3): normal occlusion > II2 > II1 (P < 0.05). The angle of tooth long axis and plane: there was significant difference in the Angel II1, II2 and normal occlusion (P < 0.05). Maxillary posterior-teeth area (coronary): II1 > II2 > normal occlusion (P < 0.05). Mandibular posterior-teeth area (coronary): II2 > normal occlusion > II1 (P < 0.05). The dental arch of Angel II1 was narrow and long in shpape, and the dental arch of Angel II2 was wide and short in shape. Sagittal discordant existed in the anterior of Angel II1, such as lip-side incline of maxilla and mandible. Coronal discordant existed in the median and posteior of Angel II1, such as palatine-side incline of the maxillary dental arch, and buccal-side incline of the mandible. Sagittal discordant existed in the anterior of Angel II2, e.g. lingual-side incline of the maxilla and mandible. No discordant existed in the posterior section of Angel II2. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Bone mineral density of cancellous bone in edentulous areas: quantitative CT measurement Huang Ying1, Zhang Hui1, Cai Yue1, Zeng Fan-gang2, Guo Ling1 2017, 21 (36):  5775-5780.  doi: 10.3969/j.issn.2095-4344.2017.36.007 Abstract ( 394 )   PDF (1008KB) ( 227 )   Save BACKGROUND: The bone mineral density (BMD) in unit volume can be accurately measured with the theory of quantitative CT. After tooth loss, bone resorption certainly exists in the alveolar bone healing. Therefore, it is important to accurately evaluate the BMD of cancellous bone in the plantation area before implantation. OBJECTIVE: To evaluate the changes in BMD of alveolar cancellous bone after the loss of tooth, and explore whether the BMD shows the differences in different genders, ages and dental sites.   METHODS: Corrected voxel values were obtained from the cone-beam CT with the theory of quantitative CT. Ninety patients underwent cone-beam CT, and their BMD (mg/cm3) in dentulous areas and control areas (homonymous region of the same jaw) was obtained. RESULTS AND CONCLUSION: The BMD of alveolar cancellous bone reduced after the loss of tooth (P < 0.001). The BMD reduction of the edentulous cancellous bone, normal cancellous bone and the cancellous bone after tooth loss had no correlation with gender. The BMD reduction of the edentulous cancellous bone and the cance llous bone after tooth loss was not associated with age (P > 0.05), while the BMD of the control area decreased with increasing age (P < 0.05). The order of the BMD of cancellous bone was as follows: mandibular posterior region > mandibular anterior region > maxillary anterior region > maxillary posterior region. To conclude, quantitative CT is a available method for detecting the changes in the BMD of alveolar cancellous bone after tooth loss. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Three-dimensional reconstruction of the nasomaxillary complex and upper airway following rapid maxillary expansion by cone-beam CT Luo Chun-hua1, Zheng Zhi-jun2, Xu Wei-hua1, Wang Qing-yun2 2017, 21 (36):  5781-5786.  doi: 10.3969/j.issn.2095-4344.2017.36.008 Abstract ( 462 )   PDF (1150KB) ( 260 )   Save BACKGROUND: Two-dimensional radiographs and plaster models are used to evaluate the changes in the maxillary bone and airway after rapid maxillary expansion, but the shortcomings like distortion, one-sidedness, and overlapping appear. Cone-beam CT can effectively solve the above problems and achieve the three-dimensional reconstruction and measurement of the maxillary bone and airway.  OBJECTIVE: To investigate the morphological changes of nasomaxillary complex and upper airway in adolescent patients with malocclusion after rapid maxillary expansion by cone-beam CT and Dolphin software. METHODS: Thirty adolescent patients with malocclusion were enrolled to receive rapid maxillary expansion. All patients underwent cone-beam CT examination before and after treatment, and Dolphin software was used for image processing, three-dimensional reconstruction, fixed point and measurement, to evaluate the morphological changes of the nasomaxillary complex and upper airway. RESULTS AND CONCLUSION: After treatment, the nasal cavity and maxillary width was increased by (2.13±1.80) and (4.12±2.15) mm, respectively (P < 0.05); the coronal diameter and area of the airway on the hard plate was increased by (3.30±2056) mm and (75.37±53.92) mm2, respectively (P < 0.05), and all above indexes showed significant difference compared with baseline. While the sagittal diameter of the airway on the hard plate showed no significant changes. After treatment, the upper airway showed a significant increase in the area and volume at the nasopharynx, which was increase by (33.57±57.10) mm2 and (1 009.59±1 350.91) mm3, respectively (P < 0.05). The upper airway showed no significant changes in the area and volume at the velopharynx and glossopharynx, as well as the height at each part. To conclude, in the growing patients with malocclusion after rapid maxillary expansion, the nasomaxillary complex and area and volume of upper airway at the nasopharynx showed a significant increase, but the airway at the velopharynx and glossopharynx reveal no significant changes. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Synovial inflammation of a rabbit model of early-stage knee osteoarthritis induced by low concentration of papain at different time points Zhang Kang-le1, Guo Jia-yi2, Liu Yuan3, Fan Yi-ming4, Gao Shan4, Li Feng2, Guo Yan-xing2 2017, 21 (36):  5787-5792.  doi: 10.3969/j.issn.2095-4344.2017.36.009 Abstract ( 381 )   PDF (5277KB) ( 282 )   Save BACKGROUND: Synovitis plays an important role in the occurrence and development of early knee osteoarthritis. OBJECTIVE: To compare synovial inflammation in a rabbit mode of knee osteoarthritis induced by injecting low concentration of papain at different time points, thus providing reference for the study on synovitis in knee osteoarthritis. METHODS: Twenty-four New Zealand white rabbits were divided randomly into four groups, and received the  injection of 0.5 mL mixture of 2% papain with 0.03 mol/L L-cysteine into the right knee at 1, 4 and 7 days, respectively. The model rabbits were respectively sacrificed at 1, 2 and 3 weeks after the last injection, and the rabbits in the blank control group were killed at 3 weeks. The local skin temperature and circumference of the knee were recorded, and the synovium and infrapatellar fat pad were separated from the right knees for histopathological observation and ELSA. RESULTS AND CONCLUSION: At the 1st week after modeling, joint effusion was significantly increased, local skin temperature and circumference of knee joint were higher than those at the 2nd, and 3rd weeks. The levels of interleukin-1, tumor necrosis factor-α and matrix metalloproteinase-13 in the synovium in the three experimental groups were higher than those in the blank control group at 1, 2 and 3 weeks after modeling; the levels peaked in the 1st week, but no significant fluctuation appeared in the 2nd and 3rd weeks. There were synovial tissue hyperplasia, thickening, and inflammatory cell infiltration in the 1st, 2nd and 3rd weeks, and the proliferation of synovial tissue increased significantly with time. These findings indicate that the intra-articular injection of low concentration of papain and 0.03 mol/L L-cysteine mixtures contributes to a rabbit model of knee synovial inflammation within 1 week, with significantly joint effusion. However, significant synovial tissue thickening and vascular hyperplasia are observed; meanwhile, the joint effusion is decreased obviously. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | Related Articles | Metrics

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Establishment of a C57 mouse model of osteoporosis with calvarial critical-size defects Luo Dao-wen1, Huang Kui1, Wang Lei1, Luo Shi-hong1, Rao Peng-cheng1, Xiao Jin-gang1, 2 2017, 21 (36):  5793-5798.  doi: 10.3969/j.issn.2095-4344.2017.36.010 Abstract ( 580 )   PDF (4233KB) ( 306 )   Save BACKGROUND: Bilateral ovariectomy is a most commonly used method to establish an animal model of postmenopausal osteoporosis. Up to now, little is reported on the C57 mouse model of osteoporosis with calvarial critical-size defects. OBJECTIVE: To establish the C57 mouse model of osteoporosis with calvarial critical-size defects. METHODS: Thirty-six C57 mice aged 8 weeks were randomly divided into two groups: the mice in model group received bilateral ovariectomy, and the same weight of fat tissues around the ovaries of the other mice were cut as control group. At 6 weeks after modeling, the mouse femur was removed for micro-CT scan and hematoxylin-eosin staining to testify whether there is a success or failure in animal modeling. Afterwards, six mice were respectively selected from each group, and two round calvarial defects with a diameter of 4 mm were symmetrically made on the parietal bone. The defect healing was evaluated by micro-CT scan at 8 weeks after modeling. RESULTS AND CONCLUSION: At 6 weeks after modeling, the bone volume fraction, bone surface to volume ratio, trabecular thickness, trabecular number, trabecular spacing and bone mineral density in the modeling group were significantly lower than those in the control group (P < 0.05). In the model group, there were loosen or fractured trabeculae, and enlarged medullary cavity. At 8 weeks after bone defects, showed no significant micro-CT changes in the defect region in both two groups. These findings implicate a success in establishing the C57 mouse model of osteoporosis with calvarial critical-size defects. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Establishing an animal model of bisphosphonate-related osteonecrosis of the jaw Wu Shi-chao1, Wang Ying-shu2, Xuan Bin1, Zhang Jian1 2017, 21 (36):  5799-5805.  doi: 10.3969/j.issn.2095-4344.2017.36.011 Abstract ( 343 )   PDF (4987KB) ( 295 )   Save BACKGROUND: Bisphosphonates-related osteonecrosis of the jaw (BRONJ) is thought to be caused by trauma to dentoalveolar structures after dental extraction and implantation that have a limited capacity for bone healing followed by infection, suppuration and pain, further inducing equestration, but the pathogenesis is poorly understood. OBJECTIVE: To establish a stable animal model of BRONJ, and to observe its clinical manifestations, radiological changes and pathological characters, thereby paving ways for further understanding the pathogenesis of BRONJ. METHODS: Twenty-four female Sprague-Dawely rats were randomly allocated into experimental and control groups (n=12 per group). The rats in the experimental group were given the intraperitoneal injection of 0.2 mg/kg zoledronic acid, and the controls received the intraperitoneal injection of same volume of normal saline, three times weekly for consecutive 12 weeks. Subsequently, left first mandibular molars were extracted under general anesthesia, and the bone healing was observed. At 8 weeks after tooth extraction, all the rats were euthanized. The rat left jaws were examined by X-ray and micro-CT to explore the imaging changes. The histopathological characteristics of the mandibular soft and hard tissues were investigated by hematoxylin-eosin staining and Masson staining, to further testify the BRONJ model. RESULTS AND CONCLUSION: At 8 weeks after tooth extraction, the wound was unable to heal, and nonvital bone tissues were visible in the experimental group. The findings revealed on radiographies and pathological sections were in accordance with the characteristics of BRONJ. Masson staining results showed slender collagen fibrils around the dental extraction wound were slender in the experimental group. These results indicate that the intraperitoneal injection of zoledronate combined with tooth extraction can induce BRONJ in rats. The soft tissue toxicity and anti-angiogenesis of zoledronic acid can promote the occurrence of BRONJ, and the local acidic microenvironment caused by trauma probably is involved in the occurrence of BRONJ. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Sciatic nerve regeneration in a rat model of brain injury at different locations Ma Jian-jun1, He Xin-ze2, Wang Hao-qi1, Sun Bo1, Gao Yun-feng1, Fu Shi-jie1, Wang Pei1 2017, 21 (36):  5806-5811.  doi: 10.3969/j.issn.2095-4344.2017.36.012 Abstract ( 355 )   PDF (5539KB) ( 256 )   Save BACKGROUND: Previous studies have shown that traumatic brain injury can promote the regeneration of peripheral nerve by reducing scar collagen in nerve endings. OBJECTIVE: To investigate the effect of brain injury at different locations on the ipsilateral rat sciatic nerve regeneration. METHODS: Ninety-nine healthy male Sprague-Dawley rats were equivalently randomized into three groups: group A, right sciatic nerve transection; group B, right sciatic nerve transection combined with right brain injury; and group C, right sciatic nerve transection combined with left brain injury. All of transected nerves were sutured under microscope. Classical Feeney method was used to establish a model of traumatic brain injury. At 4, 6, 8, 10 and 12 weeks after modeling, the sciatic functional index (SFI) was calculated by measuring footprint. At 4, 8 and 12 weeks after modeling, the bilateral gastrocnemius were harvested for determining wet weight and calculate wet weight ratio, followed by acetylcholinesterase staining at the motor end plate to detect the absorbance values. At 4, 8 and 12 weeks after modeling, fluoro-gold retrograde tracing was used to trace L4-5 vertebrae for 1 week, and the number of spinal cord anterior horn motor neurons positive for fluoro-gold was detected and calculated by fluorescence microscope. RESULTS AND CONCLUSION: The SFI value in each group was gradually improved with time. The SFI value was significantly higher in the groups B and C than the group A at 4 and 6 weeks after modeling (P < 0.05), and was further improved in the group B at 8 weeks compared with the groups A and C (P < 0.05). The wet weight ratio of gastrocnemius showed no significant difference among groups at 4 weeks after modeling (P > 0.05), and the group B showed a significantly higher wet weight ratio than the other groups from the 8th week (P < 0.05). Compared with the groups A and C, the absorbance values of motor endplate in group B appeared to be a significant increase at the beginning of the 8th week (P < 0.05). At 4 and 6 weeks after modeling, the number of spinal cord anterior horn motor neurons positive for fluoro-gold was significantly nigher in the groups B and C than in the group A, and the number was significantly higher in the group B than the groups A and C at 12 weeks (all P < 0.05). These finding manifest that brain injury can promote the repair of ipsilateral sciatic nerve injury, thus proving theoretical reference for unveiling the mechanism by which traumatic brain injury promotes peripheral nerve regeneration.  中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Histomorphological changes and stage development of the skin and hair follicle in neonatal mice Shi En1, Liu Ying-qin2 2017, 21 (36):  5812-5817.  doi: 10.3969/j.issn.2095-4344.2017.36.013 Abstract ( 760 )   PDF (5168KB) ( 286 )   Save BACKGROUND: There are many researches on the mouse skin morphology and development in embryonic period, but we have a poor understanding of the histomorphological evolution process of the skin and hair follicle after birth. OBJECTIVE: To explore the morphological changes and rules of the newborn mouse skin and hair follicle development. METHODS: The thickness of the back skin from the 1-12-day-old mice was analyzed using Image J software through conventional paraffin-embedded section and hematoxylin-eosin staining methods. The morphology of the hair follicle was observed under an optical microscope, and the number of hair follicles and vesicle-shaped structures were recorded. The development of hair follicles according to the developmental characteristics was divided into four periods, in comparison with Ralf Paus staging. RESULTS AND CONCLUSION: On the early stage of hair follicle formation (1-4 days), the newborn mice appeared with thinnest skin [(405.36±26.60) μm in thickness] on the day of birth, and there was no adipose tissue in hypodermis and few hair bulbs in epidermis. On day 2, the skin was thickened to (927.11±27.25) μm, with more dermal fibroblasts, and the horny cells from the stratum basale migrated to forming hair papilla. On days 3-4, the skin was thinned to (738.60±82.07) μm, increasing hair follicles and expanded hair bulbs were observed, with the dermis covered by dermal sheath. On the middle stage of hair follicle formation (5-7 days), the skin was thickened again on day 5, and became thickest [(2 369.57±34.06) μm in thickness] on day 7, there were increased number of hair follicles, hair bulbs and vesicle-shaped structures, the internal dermal sheath was extended into the epidermis to form hair roots, the dermal sheath was differentiated into external root sheath, and the internal root sheath extended deeply to form a closed germinal matrix. On the later stage of hair follicle formation (8-9 days), the skin thickness was decreased to (1 743.37±75.05) μm on day 8 and (1 987.07 ±18.65) μm on day 9; the hair papilla was surrounded by hair matrix; hair canal and hair shaft gradually formed, and the growing internal root sheath extended into the deep layer, forming more hair roots. On the maturation sage of hair follicle (10-12 days), the skin was thickened to          (2 399.33±27.00) μm; the number of both hair follicles and vesicle-shaped structures was about 30; the hair shaft lengthened, reaching the muscle layer, which grew upward through the hair canal and further crossed the epidermis to form the hair that could be observed by the naked eye. These findings suggest that there is synchronical or non-synchronical correlation between the skin development and hair follicle formation at the neonatal mouse back, presenting with the ascendant curve. The development process of hair follicle is imbalanced and different, and staging of hair follicle formation is available for observing the differentiation progress of hair follicle. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Serum metabolomic profiling of acute complete spinal cord transection in macaques Tang Tao1, Cheng Jian-hua2, Yang Shu-guang1, Gao Jian1, Huang Tao1, Wang Bin1, Dong Fang-ting2, Liu Shao-jun1 2017, 21 (36):  5818-5823.  doi: 10.3969/j.issn.2095-4344.2017.36.014 Abstract ( 319 )   PDF (1219KB) ( 228 )   Save BACKGROUND: Non-targeted metabolomic profiling is used to uncover metabolic changes and to identify relationships between metabolites and spinal cord injury, which contributes to further understanding the pathophysiological process and mechanisms of secondary spinal cord injury. OBJECTIVE: To detect and analyze the serum metabolite changes after complete spinal cord transaction in macaques, explore its relationship with the pathophysiological progress of spinal cord injury, and screen the potential biomarkers. METHODS: Five adult macaques were selected, in which the models of complete spinal cord transaction were established. The serum metabolic features were detected using a non-targeted metabolic profiling strategy based on gas chromatography time-of-flight mass spectrometry at 1 day before modeling, 3 hours (superacute phase) and 3 days (acute phase) after modeling. After compared with the spectrometry profiling, recognizing the metabolites, searching for differential metabolites and the related metabolic pathways, the pathophysiological process and mechanisms were analyzed. RESULTS AND CONCLUSION: Three hundred and fifty-eight chromatographic peaks were obtained for subsequent data analysis. Fourteen metabolites, including low-molecular-weight organic acid, amino acids, fatty acid and carbohydrate, were identified as differential metabolites. To conclude, the acute phase of complete spinal cord transection is closely related to some metabolic pathways, such as amino acid metabolism, tricarboxylic acid cycle and pyruvate metabolism. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Passive mechanical behaviors of mammal extraocular muscles: a comparison among fox, pig and sheep Bai Ya-jia, Gao Zhi-peng, Chen Wei-yi 2017, 21 (36):  5824-5829.  doi: 10.3969/j.issn.2095-4344.2017.36.015 Abstract ( 332 )   PDF (4057KB) ( 211 )   Save BACKGROUND: The extraocular muscles control the movement of the eyeball, and its biomechanics is essential for studying eye movement. OBJECTIVE: To determine the differences in mechanical properties of the extraocular muscles in different mammals. METHODS: This was an in vitro study. The extraocular muscles were extracted from foxes, pigs and sheep, and then we used an Instron 5544 tester to perform uniaxial experiments under the same load. Ogden hyperelastic models of each animal extraocular muscle were obtained based on the experimental data, and the passive mechanical behaviors of the extraocular muscle were compared statistically among different animals. RESULTS AND CONCLUSION: The order of load-strain values was as follows: fox > sheep > pig. The fitted curve of each animal extraocular muscle was well in accordance with the mean data. There were significant differences in the passive mechanical behaviors of extraocular muscles among mammals, including hyperelastic parameters and stress response at the same load level. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Ultrasound-induced transdermal drug delivery to the stellate ganglion as a countermeasure to sub-health state Huang Shu-ting1, Zeng Qing2, Tang Xin-qun3, Huang Ying-yi4, Shao Xiao-hui4, Wang Ying-jie5, Huang Guo-zhi2 2017, 21 (36):  5830-5834.  doi: 10.3969/j.issn.2095-4344.2017.36.016 Abstract ( 355 )   PDF (1067KB) ( 281 )   Save BACKGROUND: Stellate ganglion block is feasible for the patients in sub-health status, but it is invasive and the patient compliance is poor. OBJECTIVE: To investigate the clinical effectiveness of ultrasound-induced transdermal drug delivery for reducing the hyperactivity of the cervical sympathetic ganglia in the sub-health status. METHODS: Sixty-nine participants in sub-health state from different age levels and professions were recruited and were randomly divided into treatment (n=31) and control (n=38) groups. The treatment group underwent ultrasound-induced transdermal drug delivery to the cervical sympathetic ganglia, while the control group received psychological counseling on sub-health education and behavior intervention. All patients were assessed with Sub-Health Measurement Scale Version1.0, and the Medical Outcomes Study 36-Item Short-Form Health Survey prior to and post treatment, along with clinical curative effect assessment. RESULTS AND CONCLUSION: After treatment, 29 participants in the treatment group were improved or recovered from sub-health, with an effective rate of 93.5%. Compared with the control group, the scores were significantly improved in the treatment group. To conclude, ultrasound-induced transdermal drug delivery to the stellate ganglion has a significant effect on sub-health state. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | Related Articles | Metrics

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Nalmefene improves prognosis in patients with a large cerebral infarction: study protocol for a randomized controlled prospective trial Sun Jing, Li Xiao-ping, Wang Ting-ting, Hou Wei-chen 2017, 21 (36):  5835-5840.  doi: 10.3969/j.issn.2095-4344.2017.36.017 Abstract ( 321 )   PDF (1046KB) ( 247 )   Save BACKGROUND: Occlusion of the middle cerebral artery trunk can cause large infarctions. Clinically, thrombolytic therapy, defibrillation, vasodilation, and surgery are often used to treat these large infarctions. However, the therapeutic efficacy of these therapeutic interventions in promoting prognosis remains controversial. Nalmefene, an opioid receptor antagonist, exhibits a neuroprotective effect. Few clinical studies are reported on the therapeutic efficacy of nalmefene in the treatment of large cerebral infarctions. OBJECTIVE: To investigate the therapeutic efficacy of nalmefene in restoring the neurologic function of patients with middle cerebral artery trunk infarction in comparison with conventional treatment as a control. METHODS: A total of 236 patients with middle cerebral artery trunk infarction who will receive treatment at the First Hospital of Jilin University, China will be randomly divided into a control group (n=116) and a nalmefene group (n=120). Patients in the control group will receive conventional treatment. Patients in the nalmefene group will receive 10 successive days of intravenous nalmefene hydrochloride injection based on conventional treatment. The primary outcome of this study is the effective rate at 20 days (10 days after treatment). The secondary outcomes of this study include (1) the National Institutes of Health Stroke Scale (NIHSS) score at 20 days, used to evaluate neurologic function deficits; (2) Glasgow Coma Scale score at 0 (before treatment) and 10 days; (3) serum level of matrix metalloproteinase 9 at 0, 5 and 10 days (before treatment and 5 and 10 days of treatment); (4) MRI perfusion imaging of the head at 0 and 10 days. This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-IOR-17013871). RESULTS AND CONCLUSION: Preliminary experiment results revealed that compared with the control group, NIHSS score was signficiantly decreased, effective rate was increased, Glasgow Coma Scale score was significantly increased, serum level of matrix metalloproteinase 9 was significantly decreased, cerebral blood flow and cerebral blood volume on the lesion side were signficiantly increased, and the mean transit time of contrast agent on the lesion side was significantly shortened in the nalmefene group. Findings from this study will provide clinical evidence for use of nalmefene in combination with conventional treatment for large cerebral infarctions and provide data support that this combined therapy can improve the prognosis in patients with large cerebral infarctions. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Establishment of an individualized three-dimensional finite element model of type A coronary artery lesions Han Di, Wang Yue-xi, A Rong, Zhang Ying-jun, Wang Chun-yan 2017, 21 (36):  5841-5846.  doi: 10.3969/j.issn.2095-4344.2017.36.018 Abstract ( 493 )   PDF (1256KB) ( 289 )   Save BACKGROUND: A cardiac model can be established by finite element analysis based on patient’s MRI imaging data. The established model can be used to evaluate the rheological changes of the coronary artery by liquid-solid coupling. OBJECTIVE: To establish finite element models of the heart and coronary artery in patients with type A coronary artery disease using finite element analysis software, followed by three-dimensional (3D) printing, thereby providing a scientific basis for further simulation of interventional surgery. METHODS: Three patients with type A coronary artery lesions underwent MRI scanning from the aortic arch to the apex. The MRI images were then imported into the Mimics 17.0 software in Dicom format, and a complete cardiac model involving the coronary arteries was established by modeling and geometry cleanup. The 3D model was imported into Geomagic Studio 11.0 software, and was further processed. Finally, the 3D model was imported into ANSYS14.0 finite element analysis software. The finite element model with biofunction was established by attaching the material properties, followed by 3D printing on a 3D printer. RESULTS AND CONCLUSION: The 3D finite element model of type A coronary artery lesion was established successfully in three cases. The established heart model in each case presented with grid-based hexahedral solid elements. The number of solid elements was 24 532, 25 771, and 24 330, respectively. In the meanwhile, the model of each coronary branch was established: the number of element at the right coronary artery was 3 320, 3 518, and 3 310; the number of elements at the circumflex branch was 1 148, 1 176, and 1 164; and the number of elements at the anterior descending coronary artery was 1 025, 1 049, and 1 068, respectively. Afterwards, the 3D printing was performed successfully. These results suggest that the established 3D finite element model of the heart with coronary arteries, after 3D printing, displays the right coronary artery, anterior descending artery, circumflex artery and coronary sinus clearly, which paves ways for interventional simulation. Most importantly, it lays a solid foundation for the study on the blood-vessel dual-directional coupling, which is expected to be a new scientific method for rheological research. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Sclerostin: a new hope for the treatment of osteoporosis Zhang Shu-dong1, Zhu Meng-hai1, Li Shi-fei1, Yao Qi1, 2 2017, 21 (36):  5847-5854.  doi: 10.3969/j.issn.2095-4344.2017.36.019 Abstract ( 585 )   PDF (995KB) ( 266 )   Save BACKGROUND: Sclerostin has been shown to promote bone formation and decrease bone resorption, which provides a new idea for the treatment of osteoporosis. OBJECTIVE: To review the literatures related to sclerostin and osteoporosis, thereby providing theoretical basis for sclerostin applied in the treatment and prevention of osteoporosis, so as to improve the diagnosis and curative efficacy of osteoporosis.  METHODS: PubMed database was searched using the keywords of “osteoporosis, sclerostin, sclerosteosis, Wnt/β-catenin, LRP5/6, sclerostin antibody, sclerostin and expertise, romosozumab, blosozumab”. Finally, 58 pertinent articles were enrolled for analysis. RESULTS AND CONCLUSION: Sclerostin inhibits bone formation, so anti-sclerostin antibody is utilized, and animal experiments and clinical trials have shown that it can promote bone formation and inhibit bone reaorption. Phase III trial results potentially signify a significant step in achieving market approval, which support the preclinical and clinical emergence of sclerostin antibody therapies for both osteoporosis and alternative applications. The serum level of sclerostin is found to be closely related to lifestyle, but still need to be studied in depth. Increasing trial results show that sclerostin is the promising therapeutic candidate, which provides a new direction in the prevention and treatment of osteoporosis. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Coupling of osteogenesis and angiogenesis in bones Yang Jin-ting, Han Xiang-long 2017, 21 (36):  5855-5861.  doi: 10.3969/j.issn.2095-4344.2017.36.020 Abstract ( 534 )   PDF (1138KB) ( 271 )   Save BACKGROUND: In addition to a conduit system for oxygen, nutrients and waste products, blood vessels in bones manipulate multiple aspects of bone formation and provide niches for bone marrow hematopoietic stem cells. Coupling of osteogenesis and angiogenesis plays a crucial role in bone development, maturation, ageing and diseases. OBJECTIVE: To review the architecture of bone vasculature and process of angiogenesis, and then discuss the factors regulating coupling of osteogenesis and angiogenesis. METHODS: CBM and PubMed databases were retrieved using the keywords of “osteogenesis, blood vasculature, angiogenesis” in Chinese and English, respectively. High-quality articles related to the blood vasculature and angiogenesis in bones were included, and the repetitive studies were excluded. Finally 65 eligible articles were included to explore the coupling of osteogenesis and angiogenesis. RESULTS AND CONCLUSION: The formation and stabilization of the skeletal system rely on the coordination of several different types of cellular activities, especially endothelial cells as an important source of signals that regulate chondrocytes and osteogenesis-related cells, thus allowing the coupling of angiogenesis and osteogenesis during development and regeneration. Like other organs, the vascular system in the bones exhibits a typical hierarchy; the arterial trunk branches flow into the capillary network and then converge into the large veins in the center of the bone. Vascular endothelial growth factor, fibroblast growth factor 2, platelet-derived growth factor, matrix metalloproteinases, hypoxia, and Notch signaling pathway are involved in the angiogenesis in bones. The signaling pathways and related cytokines regulating the coupling of osteogenesis and angiogenesis will provide a new treatment strategy to battle bone diseases such as osteoporosis, bone tumor, bone fracture and bone repair. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Correlation of insulin-like growth factor-1 and bone metabolism-related indexes in postmenopausal osteoporosis Dong Mei, Wu Jian, Han Xing-mei, Jin Shu-xia 2017, 21 (36):  5862-5867.  doi: 10.3969/j.issn.2095-4344.2017.36.021 Abstract ( 359 )   PDF (1348KB) ( 232 )   Save BACKGROUND: Increasing evidence has shown that insulin-like growth factor-1 (IGF-1) plays a regulatory role in bone metabolism and increases bone formation, stimulates osteoblast number and activity, as well as reduces osteoclast differentiation and bone resorption. The mechanism of IGF-1 is an issue of concern. OBJECTIVE: To review the research advance in IGF-1 and the bone metabolism-related indexes in postmenopausal osteoporosis. METHODS: The first author searched the PubMed and CNKI databases between January 2012 and July 2016 using the keywords of “postmenopausal osteoporosis, insulin-like growth factor, bone metabolism, biochemical markers” in English and Chinese, respectively. The repetitive articles were excluded, and 36 eligible articles were enrolled for overview. RESULTS AND CONCLUSION: Bone resorption is increased in postmenopausal woman through the regulation of a variety of cytokines, in which IGF-1 in the blood is combined with IGF binding protein 3, making growth hormone play its biological role. In addition, the growth hormone in the blood directly acts on the adipose tissue, and muscle and bones. Growth hormone exerts a direct effect on bone tissue, promotes osteoblast maturation and differentiation, and enhances the expression of collagen and non-collagen through IGF-1-mediated indirect effect, thus promoting bone formation. The process of bone metabolism is able to reflect the activities of osteoblasts and osteoclasts and the changes of bone matrix and bone mineralization. In vitro experiments show that IGF-1 stimulates the proliferation of osteoblast precursors and differentiate into osteoblasts in a dose-dependent manner, promotes the expression of osteogenic markers such as alkaline phosphatase, type I collagen, and osteocalcin, and also stimulates the activity and number of osteoclasts. However, there are few clinical reports and few observation indicators, resulting in a lack of reference range for the detection and treatment of osteoporosis, which needs further exploration. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Thickening of the long bone: mechanisms and clinical implications Liu Zhen-dong1, Zhou Da-peng2, Qin Si-he3 2017, 21 (36):  5868-5872.  doi: 10.3969/j.issn.2095-4344.2017.36.022 Abstract ( 676 )   PDF (1070KB) ( 250 )   Save BACKGROUND: The thickening of living bone is an important natural rule, and genetic, nutritional and endocrine factors play critical roles in the bone thickening; however, these factors are site-blind. OBJECTIVE: To analyze the mechanism underlying the thickening of the long bone. METHODS: Clinical cases and literature were analyzed. Medline and CNKI databases were retrieved using the keywords of “bone growth in width, skeletal thickening, bone thickening, periosteal apposition” in English and Chinese, respectively. Totally 12 eligible articles were included for result analysis. RESULTS AND CONCLUSION: The mechanical environment of the bone plays a key role in the bone remodeling, which is a site-specific process. The thickening of the long bone is completed through the periosteal apposition, and the coupling effect of stress-angiogenesis-osteogenesis induced by overloading is the pathological basis of bone thickening. The periosteal apposition and periosteal resorption belong to a lifelong dynamic process, and the bending stress is the most important factor to maintain the periosteal osteogenesis. If the bone is shielded from bending stress to a certain extent by the metal fixators, it may lead to bone resorption and thinning, nonunion and other serious consequences. Therefore, the strength of the fixators should match the patient body mass and the thickness of the bone. The marrow cavity is a natural low stress region, so intramedullary fixation theoretically has little effect on the width growth of bone. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Regulatory factors in the articular cartilage repair of knee osteoarthritis  Zhu Yu-qi, Wang Zhi-yao, Zhang Shuai, Ning De-hua 2017, 21 (36):  5873-5878.  doi: 10.3969/j.issn.2095-4344.2017.36.023 Abstract ( 343 )   PDF (1280KB) ( 248 )   Save BACKGROUND: Knee osteoarthritis is a joint and articular cartilage degenerative disease, and its biological changes mainly include proliferation and apoptosis of chondrocytes. Articular cartilage holds poor regeneration ability, and tissue-engineered cartilage is of great significance for the articular cartilage repair, while cytokines is a major concern for this repair process. OBJECTIVE: To overview the main regulatory factors involved in the articular cartilage repair and chondrocyte apoptosis. METHODS: PubMed and WanFang databases were retrieved for the literature addressing articular cartilage repair and main regulatory factors involved in articular cartilage repair and chondrocyte apoptosis published from 1999 to 2016. Finally 44 eligible articles were included for analysis. RESULTS AND CONCLUSION: Various cytokines in different human tissues are closely related to articular cartilage repair, chondrocyte apoptosis and pathological changes of osteoarthritis, which are involved in chondrocyte damage, degradation of cartilage matrix, synovial degeneration and periostosis. There is an increase in the levels of interleukin 1β and 6, and tumor necrosis factor α following articular cartilage injury. Thereafter, blocking the expression of these cytokines can protect the articular cartilage from damage. Insulin-like growth factor and transforming growth factor play an important regulatory effect on the chondrocyte proliferation and matrix synthesis. Furthermore, various cytokines regulate the articular cartilage repair and reconstruction via complicated pathways. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Progress in the treatment and prevention of knee intra-articular adhesion Wu Hai-xiao1, 2, Wang Peng3, Zhang Chao1, 2, 4, Egiazaryan KA 1,2, Ratyev AP1,2, Melnichenko SY2, Kuzin VV1. 2, Skoroglyadov AV1,2 2017, 21 (36):  5879-5885.  doi: 10.3969/j.issn.2095-4344.2017.36.024 Abstract ( 363 )   PDF (1273KB) ( 224 )   Save BACKGROUND: Knee intra-articular adhesion has a serious impact on the postoperative patient’s daily life, but the efficacy of traditional treatment is limited. To reduce knee intra-articular adhesion is the key to improve the expectations of surgery, which is an urgent problem to be solved. OBJECTIVE: To analyze various articles concerning knee intra-articular adhesion, and summarize the research achievements in the last decade, so as to provide new ideas and methods for the prevention of knee intra-articular adhesion. METHODS: The first author retrieved PubMed database using computer and searched the relevant articles published from 2006 to 2016. The keywords were “tissue adhesions, arthrofibrosis, joint stiffness, prevent, treatment”. Totally 1 500 articles were retrieved, and finally 59 eligible articles were included in accordance with the inclusion criteria. RESULTS AND CONCLUSION: In recent years, a large number of scholars have found that trauma or surgery can cause knee joint bleeding and inflammation, which result in the increased expression of vascular endothelial growth factor and interleukin-6, enhance the activity of fibroblasts and secrete a large amount of collagen deposition, thereby causing knee intra-articular adhesion. The modification of traditional methods and application of minimally invasive technology have achieved a certain effect on the knee intra-articular adhesion, but there is still a risk for re-adhesion. A remarkable achievement has been obtained in the basic research of preventing knee adhesion with intra-articular drug that can become an effective method for preventing intra-articular adhesion, but its clinical feasibility is still controversial, and further investigation is needed to find the drug possessing exact effect and less adverse reactions. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Endoplasmic reticulum stress and apoptosis of chondrocytes Xiong Fei1, Wei Yi-shan2 2017, 21 (36):  5886-5891.  doi: 10.3969/j.issn.2095-4344.2017.36.025 Abstract ( 326 )   PDF (1084KB) ( 328 )   Save BACKGROUND: Although the unfolded protein response is a cellular protective response to the endoplasmic reticulum stress, hight-intensity or persistent endoplasmic reticulum stress can still induce cell apoptosis. Therefore, the endoplasmic reticulum stress is closely related to the occurrence and development of various diseases. OBJECTIVE: To overview the relationship between the endoplasmic reticulum stress and diseases, and the possible mechanisms. METHODS: The first author retrieved PubMed and CNKI databases by computer for the literature published from January 1999 to October 2016 using the keywords of “endoplasmic reticulum stress, apoptosis” in English and Chinese, respectively. Initially 4 883 relevant articles were searched. After exclusion of the repetitive studies finally 59 eligible articles were enrolled in accordance with the inclusion criteria. RESULTS AND CONCLUSION: The endoplasmic reticulum has been shown to play a crucial role in protein synthesis and folding process, as well as in maintenance of Ca2+ homeostasis, and synthesis of lipids and sterols places. Endoplasmic reticulum dysfunction caused by genetic or environmental damage leads to endoplasmic reticulum stress, followed by the unfolded protein response. Unfolded or misfolded proteins accumulate in the endoplasmic reticulum and trigger the endoplasmic reticulum stress, resulting in cellular homeostasis imbalance. The main consequence is apoptosis, thereby causing damage to tissues and organs. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Application status of small interfering RNA in spinal cord injury Zhao Jun, Xin Hong-jie, Xue Hui-qin, Zang Yuan-tong, Yan Jin-yu, Li Jian-feng 2017, 21 (36):  5892-5897.  doi: 10.3969/j.issn.2095-4344.2017.36.026 Abstract ( 283 )   PDF (927KB) ( 166 )   Save BACKGROUND: The connection between high-level central nervous system and spinal cord and peripheral nerve under injury level is blocked by traumatic spinal cord injury, and the whole function of the body is thereby influenced. The loss of motor function and feeling both severely affect the patient’s life quality in views of physiology, psychology, function and social economics. RNA interference is an effective method to silence target genes, which provides a new treatment strategy for spinal cord injury. OBJECTIVE: To explore the application status of RNA interference in spinal cord injury. METHODS: PubMed and CNKI databases were retrieved using the keywords of “RNA interference, RNAi, spinal cord injury” in English and Chinese, respectively. The articles addressing the application of RNA interference in spinal cord injury were collected and reviewed. RESULTS AND CONCLUSION: Totally 44 articles were enrolled. It is urgent to find a new way to treat spinal cord injury. Compared with the traditional gene silencing technology, RNA interference owing to high specificity, high efficiency, high stability and high penetrability is considered to be a new direction for the studies on the pathogenesis and treatment of spinal cord injury. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Research advances in circular RNAs Cheng Han-rong1, 2, 3, He Shao-ru2, 3, Wu Ben-qing1 2017, 21 (36):  5898-5904.  doi: 10.3969/j.issn.2095-4344.2017.36.027 Abstract ( 301 )   PDF (1112KB) ( 239 )   Save BACKGROUND: Unlike linear RNAs, circular RNAs (circRNAs) are a novel type of RNA which can form covalently closed circles and are highly expressed in eukaryotic transcriptomes. In the plenitude of naturally occurring RNAs, circRNAs and their biological role are underestimated for years. Recent studies have discovered thousands of endogenous circRNAs in mammalian cells. OBJECTIVE: To review the formation, properties, and functions of circRNAs, and their potential signi?cance in diseases. METHODS: A computer-based search for literature in CNKI and PubMed databases published from January 2000 to December 2016 was performed using the keywords of “circRNA, miRNA, function, mechanism” in English and Chinese, respectively. Finally, 62 eligible articles were included for analysis. RESULTS AND CONCLUSION: CircRNAs are largely generated from exonic or intronic sequences, and reverse complementary sequences or RNA-binding proteins are necessary for circRNA biogenesis. A majority of circRNAs that are conserved across specie are stable and resistant to RNaseR, and often exhibit tissue/developmental-stage-speci?c expression. Recent research has revealed that circRNAs can function as microRNA sponges, regulators of splicing and transcription, and modi?ers of parental gene expression. Emerging evidence indicates that circRNAs might play important roles in atherosclerotic vascular diseases, neurological disorders, prion diseases and cancer; exhibit aberrant expression in colorectal cancer; and serve as diagnostic or predictive biomarkers of some diseases. Similar to microRNAs and long noncoding RNAs, circRNAs are arousing general interest in the field of RNA and widely participate in the life process. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics