Elucidation of the signaling pathway mechanisms related to the mechanical stress-mediated bone regeneration is of great significance for improvement of bone regeneration and clinical treatment of bone-related diseases such as bone defects and bone elongation. Mechanical stress transmits mechanical stimuli into cells through the piezo channels and integrins, causing a variety of signaling pathway responses, which in turn changes transcription factor translocation, gene expression, and osteoblast differentiation to promote bone regeneration ultimately. This article reviews the research progress concerning the mechanisms related to mechanical stress-mediated bone tissue regeneration.

Over the past several decades of innovation and development, Ilizarov technique has been widely recognized and applied in correction of limb deformity and post-traumatic sequelae with outstanding clinical outcomes, which making remarkable contributions to the development of orthopaedics. There is no doubt that tissue regeneration induced by tension-stress is the core of Ilizarov technique, and a series of biological cascades contributing to tissue regeneration could be triggered by mechanical stimulation through signal transduction including bone morphogenetic proteins regulations, inflammatory responses and immune responses, angiogenic activities, stem/progenitor cell homing and other systematic effects. One of main limitations of Ilizarov technique is slow rate of new bone mineralization. To facilitate this technique application better in clinical practices, a multitude of researches of means for promoting bone mineralization have become hot spots in this field in recent years, such as physical measures, chemicals and biological therapies. With better understanding of distraction histogenesis for promoting tissue regeneration, transverse tibial bone transport has been increasingly applied to vascular disease management in lower extremity, such as diabetic foot and thromboangitis obliterans. This review focuses on the recent advances in understanding the basic biological mechanisms of Ilizarov technique and new methods for promoting bone consolidation in distraction areas, providing evidence and ideas for further mechanism investigations and approach innovations.

The process of bone healing is absolutely complicated and affected by a wide variety of factors. The quality of bone healing directly determines management approaches. Therefore, it is crucial to evaluate accurately outcomes of bone healing. The assessments of bone healing mostly used in current clinical practice are a combination of clinical manifestations and X-ray examination while computed tomography (CT) and ultrasound may be applied alternatively for particular parts and populations. As understanding of bone healing process and bone biomechanical structure is deepening in recent years, both traditional and novel assessments of bone healing have been well refined. This review will expound on the advantages, disadvantages and clinical indications of various assessments, as well as their future development trends, to provide useful information for clinicians.

Objective:To investigate the clinical effects and indications of tibial condylar valgus osteotomy (TCVO) in treating varus unicompartmental knee osteoarthritis.Methods:A retrospective analysis was conducted in 32 patients (45 knees) who suffered from varus unicompartmental knee osteoarthritis and underwent TCVO from June 2016 to June 2018. These patients were aged 65.8±8.3 (range from 52 to 79) years, including 12 males (18 knees) and 20 females (27 knees). All enrolled individuals presented obvious expansion of the lateral joint space with joint line convergence angle (JLCA) of 7.19°±2.69°. Based on the full-length standing X-ray imaging of the lower limbs at before and 2 years after surgery, the percentage of mechanical axis (%MA), femorotibial angle (FTA), hip-knee-ankle angle (HKA), lateral distal femoral angle (LDFA) and medial proximal tibial angle (MPTA) were measured and analyzed to evaluate the improvements of lower extremity alignments. The medial tibial plateau depression (MTPD), posterior proximal tibial angle (PPTA), JLCA and joint space width (JSW) were measured and analyzed to evaluate the congruency of the knee joint and shape of the tibial plateau based on positive and lateral radiographs of knee joint. In addition, visual analogue scale (VAS) and Western Ontario and McMaster Universities (WOMAC) score were evaluated to assess the clinical effects of TCVO pre-operatively and at 1 year or 2 years after surgery.Results:All patients were followed up for 33.4±7.4 (range from 25 to 40) months. Comparing to the preoperative radiological data, %MA at 2 years after surgery increased from 3.78%± 14.34% to 66.16%±9.90%, FTA from 185.41°±4.45° to 170.81°±2.87°, HKA from 169.69°±1.70° to 181.16°±2.39°, MPTA from 83.03°±3.20° to 90.84°±3.67° all with statistical significance ( P<0.05). There was no significant difference for PPTA between before (89.22°±1.52°) and 2 years (88.97°±1.57°) after surgery ( t=0.638, P=0.526). MTPD improved from -7.81°±3.27° to 5.78°±2.19° ( t=19.218, P<0.001). However, there was no significant difference for PPTA between before (81.63°±3.28°) and 2 years (82.25°± 2.21°) after surgery ( t=0.881, P=0.382). JLCA reduced from 7.19°±2.69° to 0.22°±2.09°. The medial and lateral JSW were corrected from 2.45±0.23 mm and 5.86±0.25 mm to 3.73±0.27 mm and 4.68±0.34 mm ( P<0.05), respectively. Additionally, VAS and WOMAC scores improved from 6.46±2.21 and 52.66±16.69 preoperatively to 2.94±1.72 and 19.31±14.87 at 1 year after surgery, and to 1.39±1.45 and 13.66±15.44 at 2 years after surgery, respectively ( P<0.05). Conclusion:Satisfactory early therapeutic outcomes could be achieved by TCVO in varus unicompartmental knee osteoarthritis with subluxated lateral joint and increased JLCA. TCVO can correct intra-articular varus deformity, adjust mechanical axis and relieve knee joint pain and dysfunction.

Objective:To discuss the key technique and strategy in the treatment of humeral shortening complicated with proximal deformity using a monorail external fixator.Methods:We retro-spectively reviewed 10 patients (8 males and 2 females) with humeral shortening and proximal deformity who had been treated by a monorail external fixator between March 2015 and April 2018.Their mean age was 19.6 years (range, from 15 to 27 years).The humeral shortening was complicated with proximal varus in 8 cases, and with proximal varus plus kyphosis in 2.The affected humeri were 6 to 11 cm (mean, 8.5 cm) shorter than the normal ones.Half-pins were placed onto the lateral upper arm for installation of a unilateral external fixator to correct the proximal humeral deformity immediately after proximal osteotomy.Gradual lengthening was performed after osteotomy in the middle humeral shaft.The limb function was evaluated by the Cattaneo cri-teria.Results:All patients were followed up for 15 to 41 months (mean, 20 months).The length of lengthening ranged from 5 to 12 cm (mean, 7.5 cm).The range of shoulder abduction averaged 160° (from 130° to 180°), much improved than the preoperative average value (90°).Fine ossification was observed in the lengthening part in 9 patients but dysostosis in the lengthening part occurred in one patient who was healed after iliac autografting.No such complications as pin tract infection and radial nerve injury occurred.Ac-cording to the Cattaneo criteria, 9 limbs in 8 cases were excellent and 2 cases good.Conclusions:A monorail external fixator is a reliable choice for treatment of humeral shortening complicated with proximal deformity.To obtain satisfactory clinical effects, it is essential to master the installation technique of external fixator and prevent and control complications as well.

Objective:To explore the reliability of preoperative diagnosis of low-grade infectious nonunion using haematological testing and radioisotope scanning (bone 3-phase image).Methods:A retrospective study was conducted of the 265 patients with bone nonunion who had been treated at Department of Orthopaedics, The Sixth People’s Hospital Affiliated to Shanghai Jiaotong University and at Department of Orthopaedics, The Eighth People’s Hospital Affiliated to Shanghai Jiaotong University from June 2010 to June 2018.They were 151 males and 114 females, aged from 19 to 64 years (average, 39.7 years).The nonunions occurred mainly at the tibia (113 cases) and the femur (72 cases).The preoperative results of their white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and radioisotope scanning were recorded.Taking the intraoperative pathological observations as the gold standards, the sensitivity, specificity, area under curve (AUC) of receiver operator characteristic (ROC) and Youden index were statistically analyzed respectively for every preoperative haematological tests and radioisotope scanning as well as for different combinations of the radioisotope scanning and one or more haematological tests.Results:Compared with the pathological observations, the radioisotope scanning showed a sensitivity of 80.7%, a specificity of 73.3%, an AUC of 0.770 and a Youden index of 0.540.In the combinations of radioisotope scanning and one haematological test, that of radioisotope scanning and CRP produced the largest AUC of 0.683, a sensitivity of 98.0%, a specificity of 70.3%, and a Youden index of 0.848.In the combinations of radioisotope scanning and 2 haematological tests, that of radioisotope scanning and WBC and ESR produced the largest AUC of 0.895, a sensitivity of 94.3%, a specificity of 67.3%, and a Youden index of 0.616 and all the 3 ones yielded an AUC of more than 0.880.The combination of radioisotope scanning and all the 3 haematological tests produced a sensitivity of 96.5%, a specificity of 79.7%, an AUC of 0.925 and a Youden index of 0.762.Conclusion:Combination of haematological testing and radioisotope scanning can be a reliable preoperative diagnosis of low-grade infection nonunion.

Type H endothelial cells (CD31 hiEMCN hi), a special subtype of vascular endothelial cells, are distributed mainly in endosteum and long bone metaphysis. They recruit and activate osteoprogenitor cells and promote endochondral ossification through paracrine, thereby promoting osteogenesis. On the contrary, their biological activities can be regulated by osteoclasts and osteoblasts. At the same time, the mutual regulation of type H endothelial cells is also closely related to the process of angiogenesis and osteogenesis. This article reviews the characteristics and cytokine expression profiles and the mediating role in mutual regulation of angiogenesis and osteogenesis of the cells, offering an insight for establishment of a bone regeneration strategy based on the coupling of angiogenesis and osteogenesis.

Professor Zhang Yingze, an academician of Chinese Engineering Academy, has dedicated himself to clinical medicine, scientific research and education in orthopedics for over 4 decades. In recent years, Professor Zhang, together with his research team, has made marvelous breakthroughs in various aspects of traumatic orthopedics which he is trying to put into practical transformation. The significant innovations of Professor Zhang and his colleagues include (1) establishment of an epidemiologic system for Chinese traumatic orthopedics, (2) proposal of new types of fractures, e.g., spiral tibial shaft fracture associated with posterior malleolar fracture, (3) introduction of fibular osteotomy for knee osteoarthritis and (4) new diagnosis and treatment approaches for pelvic and acetabular fractures. This paper is to discuss the academic thoughts of Professor Zhang, hoping to inspire young Chinese traumatic orthopedists to devote themselves to scientific innovations.

Objective: To study the effect of growth differentiation factor (GDF) 11-silenced bone marrow stromal cells (BMSCs) on bone regeneration in early steroid-induced osteonecrosis of the femoral head in rats. Methods: After GDF11 expression in BMSCs was inhibited by siRNA, the knockdown efficiency and transfection cytotoxicity were detected. The further experiments both in vitro (n=3) and in vivo (n=8) were divided into 4 groups respectively: blank control group (without any intervention), model group (glucocorticoid treatment), experimental group (siRNA transfection and glucocorticoid treatment) and negative control group (negative control transfection and glucocorticoid treatment). The BMSCs were induced into osteogenic differentiation. Alkaline phosphatase (ALP) staining and alizarin red staining were applied to evaluate the osteogenic differentiation ability of the cells while reverse transcription polymerase chain reaction (qRT-PCR) was employed to detect the relative expression levels of osteogenic markers. The osteogenesis in the necrotic femoral head was evaluated by microCT, H&E staining, immunohistochemistry staining and biomechanical test. Results: No transfection cytotoxicity was found (P>0.05). The ALP staining and alizarin red staining showed that the osteogenic differentiation of BMSCs in the experimental group was better than that in the model group. At the level of mRNA, the relative expression of ALP, runt-related transcription factor (Runx) 2, osteocalcin (OCN) and type Ⅰ collagen (α1) (COL1A1) in the blank control group (1.00±0.09, 1.02±0.23, 1.03±0.30 and 1.02±0.25, respectively) were significantly higher than those in the model group (0.46±0.11, 0.50±0.11, 0.35±0.01 and 0.57±0.02, respectively) but significantly lower than those in the experimental group (1.97±0.30, 0.94±0.19, 1.50±0.18 and 1.28±0.37) (all P<0.05). MicroCT images and quantitative analysis showed that the bone mass in the experimental group was significantly increased compared with the model group (P<0.05). Histological examination showed better bone regeneration and higher expression of Runx2 and COL1 in the necrotic femoral head in the experimental group than in the model group. Improved biomechanical properties were shown in the experimental group compared with the model group (P<0.05). Conclusions Silence of GDF11 expression may alleviate the inhibitory effect of glucocorticoid on osteogenic differentiation of BMSCs. Early transplantation of GDF11-silenced BMSCs may promote osteogenesis in the necrotic femoral head in rats.

PURPOSE: Asthma affects approximately 30 million patients in China; however, tiotropium data for Chinese patients is limited. This study aimed to assess the efficacy and safety of tiotropium in Chinese patients with moderate symptomatic asthma. METHODS: A post hoc subgroup analysis was conducted on 430 Chinese patients pooled from two 24-week, replicate phase 3 trials (NCT01172808 and NCT01172821), in which they received once-daily tiotropium 2.5 µg (Tio R2.5) or 5 µg (Tio R5) (n = 106 or 109, respectively), twice-daily salmeterol 50 µg (Sal 50) (n = 110), or placebo (n = 105), while maintaining inhaled corticosteroids (ICS). The co-primary endpoints assessed in week 24 were forced expiratory volume in 1 second (FEV1) peak0–3h response, trough FEV1 response, and responder rate as assessed using the Asthma Control Questionnaire (ACQ). RESULTS: For both FEV1 peak0–3h responses and trough FEV1 responses, the mean treatment differences were greater for Tio R2.5, Tio R5, and Sal 50 compared with placebo at 0.249 L, 0.234 L, and 0.284 L, and 0.172 L, 0.180 L, and 0.164 L, respectively (P< 0.001). The ACQ responder rate in placebo, Tio R2.5, Tio R5, and Sal 50 was 58.7%, 62.3%, 59.3%, and 69.1%, respectively. Furthermore, 11 (2.6%) of 430 patients had serious adverse events (Tio R5, n = 4; Tio R2.5, n = 1; Sal 50, n = 1; and placebo, n = 5). CONCLUSIONS: Once-daily tiotropium, as add-on to medium-dose ICS, was effective and well tolerated for Chinese patients with moderate symptomatic asthma, consistent with the main analysis.
Adrenal Cortex Hormones ; Adult ; Asian Continental Ancestry Group ; Asthma ; China ; Forced Expiratory Volume ; Humans ; Salmeterol Xinafoate ; Tiotropium Bromide