Corynoline Suppresses Osteoclastogenesis and Attenuates ROS Activities by Regulating NF-κB/MAPKs and Nrf2 Signaling Pathways.

Declining estrogen production in postmenopausal females causes osteoporosis in which the resorption of bone exceeds the increase in bone formation. Although clinical drugs are currently available for the treatment of osteoporosis, sustained medication use is accompanied by serious side effects. Corydalis bungeana Herba, a famous traditional Chinese herb listed in the Chinese Pharmacopoeia Commission, constitutes various traditional Chinese Medicine prescriptions, which date back to thousands of years. One of the primary active components of C. bungeana Turcz. is Corynoline (Cor), a plant isoquinoline alkaloid derived from the Corydalis species, which possesses bone metabolism disease therapeutic potential. The study aimed at exploring the effects as well as mechanisms of Cor on osteoclast formation and bone resorption. TRAcP staining, F-actin belt formation, and pit formation were employed for assessing the osteoclast function. Western blot, qPCR, network pharmacology, and docking analyses were used for analyzing the expression of osteoclast-associated genes and related signaling pathways. The study focused on investigating how Cor affected OVX-induced trabecular bone loss by using a mouse model. Cor could weaken osteoclast formation and function by affecting the biological receptor activators of NF-κB and its ligand at various concentrations. Mechanistically, Cor inhibited the NF-κB activation, and the MAPKs pathway stimulated by RANKL. Besides, Cor enhanced the protein stability of the Nrf2, which effectively abolished the RANKL-stimulated ROS generation. According to an OVX mouse model, Cor functions in restoring bone mass, improving microarchitecture, and reducing the ROS levels in the distal femurs, which corroborated with its in vitro antiosteoclastogenic effect. The present study indicates that Cor may restrain osteoclast formation and bone loss by modulating NF-κB/MAPKs and Nrf2 signaling pathways. Cor was shown to be a potential drug candidate that can be utilized for the treatment of osteoporosis.

Comparison of ESIN and other minimally invasive techniques for anterior pelvic ring injury: a finite element analysis and case-control study.

OBJECT: A novel technique, percutaneous elastic stable intramedullary nail fixation (ESIN), proposed by our team for the treatment of anterior pelvic ring injury. Finite element analysis and retrospective case-control study were used to compare biomechanical properties and clinical outcomes between ESIN and other techniques. METHODS: Four groups of finite element models of pelvic anterior ring injury were simulated, including ESIN (model A), retrograde transpubic screw fixation (RTSF, model B), subcutaneous internal fixator (model C), and external fixator (model D), and a vertical downward load of 500 N was applied to the S1 vertebral endplate. Stress and displacement distributions of intact pelvis, displacement distributions of pubic fracture fragments, and stress distributions of fixation devices were analyzed. Then 31 patients with anterior pelvic ring injury (15 in the ESIN group and 16 in the RTSF group) were reviewed. Clinical outcomes were evaluated at the final follow-up. Postoperative complications were also recorded. RESULTS: Under 500N loading, the intact stability of the pelvis was compared as follows: model B (20.58 mm, 121.82 MPa), model A (20.80 mm, 129.97 MPa), model C (22.02 mm, 141.70 MPa), and model D (22.57 mm, 147.06MPa). The regional stability of superior pubic ramus was compared as follows: model B (9.48 mm), model A (10.16 mm), model C (10.52 mm), and model D (10.76 mm). All 31 patients received follow-up at least 12 months post-surgery (range 12-20 months). Age, sex, injury mechanism, fracture type, time between the injury and operation, American Society of Anesthesiologists score, intraoperative blood loss, hospital stay, follow-up period, time to union and Majeed scores did not differ significantly between the two groups (P>0.05). However, the differences in the duration of unilateral surgery, unilateral intraoperative fluoroscopy and one-time success rate were significant (P<0.05). CONCLUSIONS: With sufficient biomechanical stability and minimally invasive advantage, the percutaneous technique using ESIN can be used to successfully treat anterior pelvic ring injuries. In addition, advantages over RTSF include a shorter duration of surgery, reduced requirement for intraoperative fluoroscopy and a higher one-time success rate. ESIN therefore constitutes a good alternative to RTSF.

Nuciferine improves random skin flap survival via TFEB-mediated activation of autophagy-lysosomal pathway.

Due to their simplicity and reliability, random-pattern skin flaps are commonly utilized in surgical reconstruction to repair cutaneous wounds. However, the post-operative necrosis frequently happens because of the ischemia and high-level of oxidative stress of random skin flaps, which can severely affect the healing outcomes. Earlier evidence has shown promising effect of Nuciferine (NF) on preventing hydrogen peroxide (H2O2)-induced fibroblast senescence and ischemic injury, however, whether it can function on promoting ischemic flap survival remains unknown. In this work, using network pharmacology analysis, it was possible to anticipate the prospective targets of NF in the context of ischemia. The results revealed that NF treatment minimized H2O2-induced cellular dysfunction of human umbilical vein endothelial cells (HUVECs), and also improved flap survival through strengthening angiogenesis and alleviating oxidative stress, inflammation and apoptosis in vivo. These outcomes should be attributed to TFEB-mediated enhancement of autophagy-lysosomal degradation via the AMPK-mTOR signaling pathway, whilst the restriction of autophagy stimulation with 3MA effectively diminished the above advantages of NF treatment. The increased nuclear translocation of TFEB not only restored lysosome function, but also promoted autophagosome-lysosome fusion, eventually restoring the inhibited autophagic flux and filling the high energy levels. The outcomes of our research can provide potent proof for the application of NF in the therapy of vascular insufficiency associated disorders, including random flaps.

Engineered exosomes derived from miR-132-overexpresssing adipose stem cells promoted diabetic wound healing and skin reconstruction.

The tissue reconstruction of diabetic wounds mainly depends on the proliferation and remodelling of cutaneous cells around wounds and the transplantation of random skin flaps, however, the proliferation of cells or survival of skin flaps are difficult due to the severe inflammation and other problems caused by diabetes. The stem cell-derived exosomes loaded with miRNA can be an effective therapeutic strategy for promoting diabetic wound healing. Therefore, in this study, the engineered exosomes derived from miR-132-overexpressing adipose stem cells (miR-132-exo) was obtained for promoting the healing of diabetic wounds and skin flaps. In vitro, the miR-132-exo promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs). In vivo, streptozotocin (STZ) induced diabetic mice were used to create full-thickness skin wounds and random skin flaps to further investigate the healing effect of miR-132-exo. The results showed miR-132-exo evidently enhanced the survival of skin flaps and promote diabetic wound healing, through reducing local inflammation, promoting angiogenesis and stimulating M2-macrophages polarization mediated by NF-κB signaling pathway. These novel findings demonstrated that engineered miR-132-exo can be a potent therapeutic for treating diabetic wounds and inflammatory-related disease.

Retracted: Therapeutic Effects of Resveratrol Liposome on Muscle Injury in Rats.

This publication has been retracted by the Editor due to concerns regarding the originality of the figure images.Reference:Yongzeng Feng, Zili He, Cong Mao, Xiaolong Shui, Leyi Cai. Therapeutic Effects of Resveratrol Liposome on Muscle Injury in Rats. Med Sci Monit, 2019; 25:2377-2385. DOI: 10.12659/MSM.913409.

Erratum: An injectable liposome for sustained release of tanshinone IIA to the treatment of acute blunt muscle injury by augmenting autophagy and alleviating oxidative stress.

[This corrects the article on p. 4189 in vol. 12, PMID: 32913497.].

Changes in radiological parameters during reduction of femoral neck fractures: A radiographic evaluation of cadavers.

OBJECTIVE: To investigate changes in the Garden index and other radiological parameters during reduction of femoral neck fractures. METHODS: Ten healthy, human femoral specimens were obtained. A 2.0 mm diameter Kirschner wire was implanted in the centre of the femoral head. A perpendicular osteotomy was made in the middle of the femoral neck. The distal osteotomy surface was used as the angle of rotation (pronation and supination up to 90° at 10° intervals). Anterior-posterior and lateral view radiographs were taken at different angles. The Garden index and other relevant data were analysed using the picture archiving and communication system. Changes in the area of the femoral head fovea at different rotation angles were measured. RESULTS: There were no significant differences in the Garden index between 0-30° of pronation and supination (p > .05). For angles of 40-90°, there were statistically significant differences in the Garden index (p < .05). The area of femoral head fovea decreased with increasing pronation angle, and increased with increasing supination angle. CONCLUSIONS: The Garden index does not change significantly if the angle of fracture rotation is 0-30° (in either pronation or supination) during femoral neck fracture reduction. Therefore, it is impossible to judge the rotation of fracture in this range of angles. The Garden index can detect the rotation of fracture for rotation angles of 40-90° (in either pronation or supination). Changes in the area of the femoral head fovea can help determine the rotation of femoral neck fractures. LEVEL OF EVIDENCE: Level V.

Comparison of percutaneous cross screw fixation versus open reduction and internal fixation for pelvic Day type II crescent fracture-dislocation: case-control study.

OBJECTIVE: To investigate the clinical outcomes of percutaneous cross screws internal fixation for pelvic Day type II crescent fracture-dislocation. METHODS: We reviewed 66 consecutive patients undergoing surgical treatment for Day type II crescent fracture-dislocation from June 2005 to December 2017. Percutaneous cross screws internal fixation was performed in 40 patients, and open reduction and internal fixation was performed in 26 patients. The patient characteristics, surgical complications, radiographic and clinical outcomes and were compared. RESULTS: There was no statistically difference on the mean time from injury to surgery between the two groups. The time of operation, the amount of blood loss, the length of incision, and the hospital stay were significantly shorter in the percutaneous cross screws internal fixation group. No significant difference on Matta scores and Majeed scores between the two groups. The open reduction and internal fixation group resulted in a higher rate of intraoperative hemorrhage, nerve injury, discomfort, and pain. CONCLUSION: Percutaneous cross screws internal fixation for Day II type pelvic crescent fracture-dislocation was safe and effective. Minimally invasive fixation had the advantages of short operation and hospitalization time, less intraoperative bleeding, and surgical trauma.

An injectable liposome for sustained release of tanshinone IIA to the treatment of acute blunt muscle injury by augmenting autophagy and alleviating oxidative stress.

Acute blunt skeletal muscle injury occurs frequently in sports and traffic accidents, and even leads to muscle necrosis and impaired functionality. Current treatment options for muscle injuries remain suboptimal and often result in delayed/incomplete recovery of damaged muscles. Tanshinone IIA is extracted from Salvia Miltiorrhizae, which is effective in the treatment of injury repair. But the clinical application of tanshinone IIA is limited due to its low water solubility, low permeability to biofilm and low bioavailability. In this study, tanshinone IIA liposomes were prepared to improve the bioavailability and sustained release of tanshinone IIA. The particle size, dispersion coefficient, zeta potential, encapsulation efficiency (EE) and drug loading (DL) of tanshinone IIA liposomes were 150.67 ± 27.23 nm, 0.20 ± 0.015, -8.73 ± 2.28 mV, 70.32 ± 4.04% and 15.63%, respectively. The results of quantitative real-time polymerase chain reaction (QRT-PCR) showed that tanshinone IIA liposome significantly promoted the expression of vimentin and reduce MHCIIB expression compared with other groups (P < 0.05). Western blotting showed that tanshinone IIA liposome could effectively promote the expression of autophagy-related proteins (VPS34, Beclin 1 and CTSD) and decrease p62 expression levels to treat injured muscle. Through HE, immunohistochemistry, ELISA and serological tests, we found that tanshinone IIA liposome not only effectively promoted the expression of desmin, but also reduced the expression of collagen-I and inhibited the production of pro-inflammatory factors, such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) (P < 0.05). In addition, tanshinone IIA liposome therapy significantly reduced the level of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD) after muscle injury compared with other groups (P < 0.05). In conclusion, tanshinone IIA liposome possesses an effective therapeutic effect on acute blunt muscle injury in rats by augmenting autophagy and alleviating oxidative stress. The continuous release of tanshinone IIA encapsulated by liposomes for disease treatment provide a new idea for the efficient and safe use of drugs with low lipid solubility and bioavailability for the treatment of acute blunt muscle injury and repair of other injuries.

A Nomogram for Prediction of Postoperative Pneumonia Risk in Elderly Hip Fracture Patients.

PURPOSE: Pneumonia is one of the common complications of hip fracture. This study aimed to evaluate the risk factors and apply a nomogram to predict postoperative pneumonia in elderly hip fracture patients. MATERIALS AND METHODS: From August 2014 to October 2019, 1113 hip fracture patients who were older than 65 years and underwent surgical treatment in our hospital were subjects of this study. Univariate and multivariate Cox analyses were used to identify independent risk factors. A predictive nomogram model was built, and the discrimination and calibration were determined by receiver operating characteristic and calibration plot. RESULTS: A total of 166 patients developed pneumonia after operation (14.91%, pneumonia group) while the remaining 947 patients did not (85.09%, non-pneumonia group). According to the results, body mass index (OR, 0.76, 95% CI, 0.70 to 0.84, P<0.001), serum albumin (OR, 0.86, 95% CI, 0.79 to 0.93, P<0.001), c-reactive protein (OR, 1.01, 95% CI, 1.00 to 1.92, P=0.011), functional status (OR, 2.94, 95% CI, 1.69 to 5.10, P<0.001) and time to surgery (OR, 4.56, 95% CI, 2.64 to 7.88, P<0.001) were identified as independent risk factors of pneumonia. The area under the curve value for postoperative pneumonia risk was 0.905, and the P-value of the Hosmer-Lemeshow calibration test was 0.529. CONCLUSION: Our nomogram model can be used to predict the risk of pneumonia in elderly hip fractures after surgery and provide clinicians with guidance for better perioperative intervention to improve prognosis and reduce mortality.

Paeoniflorin promotes angiogenesis and tissue regeneration in a full-thickness cutaneous wound model through the PI3K/AKT pathway.

The treatment of wounds remains a clinical challenge because of poor angiogenesis under the wound bed, and increasingly, the patients' need for functional and aesthetically pleasing scars. For the wound healing process, new blood vessels which can deliver nutrients and oxygen to the wound area are necessary. In this study, we investigated the pro-angiogenesis ability and mechanism in wound healing of paeoniflorin (PF), which is a traditional Chinese medicine. In our in vitro results, the ability for proliferation, migration and in vitro angiogenesis in human umbilical vein endothelial cells was promoted by coculturing with PF (1.25-5 µM). Meanwhile, molecular docking studies revealed that PF has excellent binding abilities to phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT), and consistent with our western blot results, that PF suppressed PI3K and AKT phosphorylation. Furthermore, to investigate the healing effect of PF in vivo, we constructed a full-thickness cutaneous wound model in rats. PF stimulated the cellular proliferation status, collagen matrix deposition and remodeling processes in vitro and new blood vessel formation at the wound bed resulting in efficient wound healing after intragastric administration of 10 mg·kg-1 ·day-1 in vivo. Overall, PF performed the pro-angiogenetic effect in vitro and accelerating wound healing in vivo. In summary, the capacity for angiogenesis in endothelial cells could be enhanced by PF treatment via the PI3K/AKT pathway in vitro and could accelerate the wound healing process in vivo through collagen deposition and angiogenesis in regenerated tissue. This study provides evidence that application of PF represents a novel therapeutic approach for the treatment of cutaneous wounds.

An injectable liposome for sustained release of icariin to the treatment of acute blunt muscle injury.

OBJECTIVES: Icariin, extracted from Epimedium, is a kind of flavonoid and possesses osteogenesis and antioxidant. This study aimed to evaluate the therapeutic effects of icariin liposome on acute blunt skeletal muscle injury in rats. METHODS: Icariin liposome was prepared by the thin-film dispersion method. After muscle injury, the corresponding treatment measures were given every day for two weeks. Recovery and mechanism of muscle injury were evaluated by QRT-PCR, HE, immunohistochemistry, malondialdehyde, superoxide dismutase and serological tests. KEY FINDINGS: The particle size, polydispersity index, zeta potential, encapsulation efficiency and drug loading of icariin liposomes were 171.37 ± 38.23 nm, 0.27 ± 0.01, -5.59 ± 1.36 mV, 78.15 ± 2.04% and 15.62%, respectively. The QRT-PCR showed that icariin liposome significantly promoted the expression of MHCIIB and vimentin. Through HE, immunohistochemistry, ELISA and serological tests, we found that icariin liposome effectively promoted desmin expression, reduced collagen I expression and inhibited the production of pro-inflammatory factors, including TNF-α and IL-6. Icariin liposome therapy significantly reduced the level of malondialdehyde and increased the activity of superoxide dismutase. CONCLUSIONS: Icariin liposome has excellent therapeutic effects on acute blunt muscle injury in rats by improving immunity, repairing cytoskeleton and cellular integrity, anti-inflammation, anti-fibrosis and antioxidant stress.

A novel percutaneous crossed screws fixation in treatment of Day type II crescent fracture-dislocation: A finite element analysis.

OBJECTIVE: Day type II crescent fracture-dislocation is a subtype of pelvic lateral compression injury. At present, there is still a controversy on the operative approach and fixation technique. We have put forward closed reduction and percutaneous crossed screws fixation for treating type-II crescent fracture-dislocation. Finite element analysis is used to compare the biomechanical properties between percutaneous crossed screws and other internal fixations. METHODS: A three-dimensional finite element model of Day type-II crescent fracture-dislocation was simulated using 5 implants, including double anterior plates (Model A), one posterior plate and one iliac screw (Model B), one sacroiliac joint screw (Model C), crossed one iliac screw and one sacroiliac joint screw (Model D), and crossed two iliac screws and one sacroiliac joint screw (Model E). 600-N stress was applied to S1 vertebral end-plate. To evaluate the biomechanical properties, the stress distribution and displacement distribution of the pelvis, stress distribution of the crescent fragment and stress distribution of plate and cannulated screw were recorded and analyzed. RESULTS: Under the loading of 600N, the maximum pelvic displacements in the finite element model were compared as follows: model E (0.070 â€‹mm), model D (0.071 â€‹mm), model A (0.080 â€‹mm), model C (0.096 â€‹mm), and model B (0.112 â€‹mm). The maximum displacements of crescent fragment were compared as follows: model E (0.018 â€‹mm), model B (0.022 â€‹mm), model D (0.023 â€‹mm), model A (0.030 â€‹mm), and model C (0.043 â€‹mm). The maximum stress of all implants were compared as follows: model D (90.01 â€‹Mpa), model E (81.60 â€‹Mpa), model C (69.07 â€‹Mpa), model A (56.51 â€‹Mpa), model B (18.29 â€‹Mpa). Model E and model D could provide better mechanical support for whole pelvic. CONCLUSIONS: With sufficient biomechanical stability and minimally invasive advantage, percutaneous crossed screw fixation is a recommended treatment for Day Type-II Crescent Fracture-dislocation. It is recommended to fix crescent fracture fragment and sacroiliac joint simultaneously during the operation. If it is difficult to fix the both position, the sacroiliac joint is preferentially fixed. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: There is a controversy on the operative approach and fixation technique of Day type-II crescent fracture-dislocation. This article proves that percutaneous crossed screw fixation is a recommended treatment for Day type-II crescent fracture-dislocation by finite element analysis.

Therapeutic Effects of Resveratrol Liposome on Muscle Injury in Rats.

BACKGROUND In this study we prepared liposome microbubbles loading resveratrol (LMLR) and evaluated its therapeutic effect on injury of gastrocnemius muscle in rats. MATERIAL AND METHODS LMLR was prepared and characterized by particle size, potential, and microscopy, and a rat model of acute blunt injury of gastrocnemius muscle was established. After treatments with resveratrol or LMLR, the therapeutic effects were evaluated by hematoxylin-eosin (HE) staining. The expression of MHCIIB and vimentin in mRNA level was measured by real-time PCR. The expression of desmin and collagen I protein was assessed by immunohistochemistry. RESULTS LMLR showed regular cycle shape in a size of ~1000 nm. LMLR was negatively charged (-30 mV). The in vitro release of LMLR was close to 80% at 10 h and 90% at 48 h. Acute gastrocnemius muscle injury was established in rats and tissue recovery was observed after LMLR treatment as evidenced by HE staining, decreased expression of MHCIIB, and increased expression of vimentin. Moreover, LMLR treatment obviously facilitated desmin expression and reduced collagen I expression. CONCLUSIONS LMLR is effective in treating acute blunt injury of gastrocnemius muscle in rats.

Upregulating mTOR/ERK signaling with leonurine for promoting angiogenesis and tissue regeneration in a full-thickness cutaneous wound model.

Wound therapy remains a clinical challenge due to the poor vascularization during the healing process and the high demand to achieve functional and aesthetically satisfactory scars. Newly-formed blood vessels are necessary for wound healing since they can deliver nutrients and oxygen to the wound area. In this study, the role of leonurine (LN), a traditional Chinese medicine isolated from Herba leonuri, in promoting angiogenesis and its function in wound healing have been investigated. The results of co-culture with human umbilical vein endothelial cells (HUVECs) demonstrated that LN treatment (5-20 µM) could promote the proliferation and migration and enhance the ability of in vitro angiogenesis through up-regulating the mTOR/ERK signaling pathway. Furthermore, a full-thickness cutaneous wound model was used to investigate the healing effect of LN in vivo. Intragastric administration of 20 mg per kg per day LN stimulated the regeneration of more blood vessels at the wound sites, which confirmed the in vitro results of promoting angiogenesis. Due to fast vascularization, the collagen matrix deposition and remodeling processes were also accelerated in LN treated wounds, resulting in efficient wound healing. In summary, LN promoted angiogenesis of endothelial cells in vitro by activating the mTOR/ERK pathway, and could efficiently enhance the angiogenesis and collagen deposition of the regenerated tissue, together with facilitating the wound healing process in vivo. This study provides evidence for LN-stimulated angiogenesis and tissue regeneration in skin wounds, especially in ischemic wounds.

Comparison of a single approach versus double approaches for the treatment of terrible traid of elbow-A retrospective study.

INTRODUCTION: Dislocation of the elbow associated with radial head and coronoid fracture, the so-called "terrible triad" of the elbow, is challenging to treat and has a history of complicated outcomes. This study is to compare the clinical outcome of a single lateral approach-the extensile splitting extensor digitorum communis (EDC) approach and combined lateral and medial (CML) approaches for the treatment of terrible traid of the elbow (TTE). MATERIAL AND METHODS: After appropriate exclusion, 60 TTE patients (28 patients in the EDC group, 32 patients in the CML group) from 2009 January to 2015 August were reviewed in this study. All included patients underwent open reduction, lateral collateral ligament complex repair, and postoperative function exercise. Surgical time, intraoperative blood loss, postoperative pain, elbow motion, MEPS score and complication rate were recorded and compared. RESULT: There were significant differences in surgery time (P < 0.05) and ulnar nerve lesion symptom, no patient suffered ulnar nerve lesion symptom in EDC group, but 5 patients in CML group suffered it. No differences were found in intraoperative blood loss, postoperative pain and heterotopic ossification (P > 0.05). Mean follow-up was 26.1 months (from 24 to 30 months), at the final follow-up, 2 patients in EDC group and 4 patients in CML group required elbow release operation, mean flexion and extension (124.1 ±â€¯14.6°and 8.3 ±â€¯5.3°), pronation and supination (73.4 ±â€¯5.3° and 74.4 ±â€¯6.0°) in EDC group were higher than CML group (114.2 ±â€¯15.0° and 17.6 ±â€¯8.0°, 69.2 ±â€¯6.9° and 70.4 ±â€¯7.5°, P < 0.05). Besides, MEPS score in the former group was also higher than the latter group (91.8 ±â€¯4.5 to 84.4 ±â€¯5.2, P < 0.01). CONCLUSION: The single lateral approach achieved better function recovery than combined lateral and medial approach, decreasing the risk of ulnar nerve lesion and surgery time for the treatment of TTE.

Comparison of three fixation methods in treatment of tibial fracture in adolescents.

BACKGROUND: Tibial fractures are the most common musculoskeletal injury in adolescents. The optimal management of tibial fractures in adolescents is controversial. In this study, we compared the outcomes including complications of three fixation methods in tibial fractures of adolescents and explored the factors associated with the complications. METHODS: A retrospective cohort study about 83 diaphyseal tibial fractures in 79 children and adolescents, who were treated with plate fixation (PF), elastic stable intramedullary nail fixation (ESINF), or external fixation (EF), was conducted. After adjustment for age, weight, energy of the injury, polytrauma, fracture level and pattern, and extent of comminution, treatment outcomes were compared in accordance with the length of the hospital stay, time to union, and complication rates including many factors. RESULTS: The mean age of the patients was 13.4 years, and their mean weight was 44.2 kg. There was a loss of reduction in two of 33 fractures treated with ESINF and four of 13 treated with EF (P < 0.001). At the time of final follow-up, three patients (two treated with EF and one treated with ESINF) had ≥2.0 cm of shortening. Four of the 32 patients (33 fractures) treated with ESINF underwent a reoperation (two due to loss of reduction and one each because of delayed union and nonunion). Six patients treated with EF required a reoperation (four due to loss of reduction, one for malunion and one for replacement of a pin complicated by infection). Two fracture treated with PF required refixation attributing to nonunion and malunion. A multivariate analysis with adjustment for baseline differences showed that EF was associated with a 7.56-times (95% confidence interval 3.74-29.87) greater risk of loss of reduction and/or malunion than ESINF. CONCLUSIONS: All three treatments had satisfactory outcomes, and EF was correlated with the highest rate of complications in our series of adolescents treated with a tibial fracture. However, we cannot currently recommend that all fractures might be suitable for ESINF. The choice of fixation will remain influenced by surgeon preference in term of expertise and experience, patient and fracture characteristics, and patients and family preferences.

Monotropein promotes angiogenesis and inhibits oxidative stress-induced autophagy in endothelial progenitor cells to accelerate wound healing.

Attenuating oxidative stress-induced damage and promoting endothelial progenitor cell (EPC) differentiation are critical for ischaemic injuries. We suggested monotropein (Mtp), a bioactive constituent used in traditional Chinese medicine, can inhibit oxidative stress-induced mitochondrial dysfunction and stimulate bone marrow-derived EPC (BM-EPC) differentiation. Results showed Mtp significantly elevated migration and tube formation of BM-EPCs and prevented tert-butyl hydroperoxide (TBHP)-induced programmed cell death through apoptosis and autophagy by reducing intracellular reactive oxygen species release and restoring mitochondrial membrane potential, which may be mediated viamTOR/p70S6K/4EBP1 and AMPK phosphorylation. Moreover, Mtp accelerated wound healing in rats, as indicated by reduced healing times, decreased macrophage infiltration and increased blood vessel formation. In summary, Mtp promoted mobilization and differentiation of BM-EPCs and protected against apoptosis and autophagy by suppressing the AMPK/mTOR pathway, improving wound healing in vivo. This study revealed that Mtp is a potential therapeutic for endothelial injury-related wounds.