l-arginine promotes angio-osteogenesis to enhance oxidative stress-inhibited bone formation by ameliorating mitophagy.

Background: Osteoporosis is one of the most common bone diseases in middle-aged and elderly populations worldwide. The development of new drugs to treat the disease is a key focus of research. Current treatments for osteoporosis are mainly directed at promoting osteoblasts and inhibiting osteoclasts. However, there is currently no ideal approach for osteoporosis treatment. l-arginine is a semi-essential amino acid involved in a number of cellular processes, including nitric production, protein biosynthesis, and immune responses. We previously reported that l-arginine-derived compounds can play a regulatory role in bone homeostasis. Purpose: To investigate the specific effect of l-arginine on bone homeostasis. Methods: Mildly aged and ovariectomized mouse models were used to study the effects of l-arginine on osteogenesis and angiogenesis, assessed by micro-computed tomography and immunostaining of bone tissue. The effect of l-arginine on osteogenesis, angiogenesis, and adipogenesis was further studied in vitro using osteoblasts obtained from cranial cap bone, endothelial cells, and an adipogenic cell line. Specific methods to assess these processes included lipid staining, cell migration, tube-forming, and wound-healing assays. Protein and mRNA expression was determined for select biomarkers. Results: We found that l-arginine attenuated bone loss and promoted osteogenesis and angiogenesis. l-arginine increased the activity of vascular endothelial cells, whereas it inhibited adipogenesis in vitro. In addition, we found that l-arginine altered the expression of PINK1/Parkin and Bnip3 in the mitochondria of osteoblast-lineage and endothelial cells, thereby promoting mitophagy and protecting cells from ROS. Similarly, l-arginine treatment effectively ameliorated osteoporosis in an ovariectomized mouse model. Conclusion: l-arginine promotes angio-osteogenesis, and inhibits adipogenesis, effects mediated by the PINK1/Parkin- and Bnip3-mediated mitophagy. The Translational Potential of this Article: L-arginine supplementation may be an effective adjunct therapy in the treatment of osteoporosis.

Novel sternoclavicular hook plate for the treatment of posterior sternoclavicular dislocation: a retrospective study.

BACKGROUND: Controversies regarding the optimal internal fixation method for posterior sternoclavicular dislocation (SCD) exist. Therefore, this study aimed to investigate the clinical efficacy of a new type of sternoclavicular hook plate for treating posterior SCD. METHODS: Eleven patients (eight men and three women) with posterior SCD who underwent treatment with the new sternoclavicular hook plate from June 2011 to January 2022 were retrospectively analyzed. The patients' ages ranged from 33 to 71 years (54.91 ± 13.58 years). Operation time, blood loss, length of hospital stay, and postoperative complications were recorded. Postoperative joint reduction and healing were evaluated using radiography and computed tomography. The Constant-Murley and Rockwood sternoclavicular joint scores were used to evaluate the functional recovery of the affected limb 12 months after surgery. RESULTS: All 11 patients were followed up for 12-24 months (18.00 ± 3.74 months). All incisions healed by first intention. The healing time ranged from 9 to 13 days (10.82 ± 1.54 days), and the joint healing time was 3-4 months (3.55 ± 0.52 months). The operation time was 45-75 min (59.55 ± 11.06 min), intraoperative blood loss was 22-58 mL (39.91 ± 11.07 mL), and the length of hospitalization was 6-14 days (9.91 ± 3.27 days). There were no complications such as infections, internal fixation failure, or nerve injury. The Constant-Murley score was 93.64 ± 9.01 at 12 months postoperatively. The Rockwood score was 13.36 ± 1.86, of which nine cases were excellent, one case was good, and one case was fair. CONCLUSION: The novel sternoclavicular hook plate is effective for the treatment of posterior SCD. This novel device can facilitate early joint functional exercises and good functional recovery.

Paroxetine Attenuates Chondrocyte Pyroptosis and Inhibits Osteoclast Formation by Inhibiting NF-κB Pathway Activation to Delay Osteoarthritis Progression.

Background: Osteoarthritis (OA), a common chronic joint disease, is characterized by cartilage degeneration and subchondral bone reconstruction. NF-κB signaling pathway-activated inflammation and NLRP3-induced pyroptosis play essential roles in the development of OA. In this study, we examine whether paroxetine can inhibit pyroptosis and reduce osteoclast formation, thereby delaying the destruction of knee joints. Methods: We employed high-density cultures, along with quantitative polymerase chain reactions and Western blotting techniques, to investigate the effects of paroxetine on extracellular matrix synthesis and degradation. The expression levels of NF-κB and pyroptosis-related signaling pathway proteins were examined by Western blotting and immunofluorescence. Furthermore, the impact of paroxetine on RANKL-induced osteoclast formation was evaluated through TRAP staining and F-actin ring fluorescence detection. To investigate the role of paroxetine in vivo, we constructed a mouse model with destabilization of the medial meniscus (DMM) surgery. Safranin O-Fast Green staining, Hematoxylin-Eosin staining, and immunohistochemistry were conducted to observe the extent of knee joint cartilage deformation. In addition, TRAP staining was used to observe the formation of osteoclasts in the subchondral bone. Results: In the in vitro experiments with ATDC5, paroxetine treatment attenuated IL-1ß-induced activation of the pyroptosis-related pathway and suppressed extracellular matrix catabolism by inhibiting the NF-kB signaling pathway. In addition, paroxetine treatment decreased the expression of RANKL-induced osteoclast marker genes and reduced osteoclast formation. In animal experiments conducted in vivo, mice treated with paroxetine exhibited thicker knee cartilage with a smoother surface compared to the DMM group. Additionally, the formation of osteoclasts in the subchondral bone was reduced in the paroxetine-treated mice. Further analysis revealed that paroxetine treatment played a role in preserving the balance of the extracellular matrix and delaying knee joint degeneration. Conclusion: Paroxetine can inhibit pyroptosis and reduce osteoclast formation via inhibiting the NF-κB signaling pathway, suggesting that it may have therapeutic effects in patients with OA.

[Novel sternoclavicular hook-plate for treatment of proximal clavicle fracture with dislocation of sternoclavicular joint].

OBJECTIVE: To explore the efficacy of a novel sternoclavicular hook-plate for treatment of proximal clavicle fracture with dislocation of sternoclavicular joint. METHODS: Retrospective analysis of 13 cases of proximal clavicle fracture with dislocation of sternoclavicular joint treated with sternoclavicular hook-plate from June 2011 to January 2019 in our department. There were 9 males and 4 females, aged 26 to 78 years old, with an average age of (54.08±13.91) years old. All the patients had closed injuries without damage of blood vessels and nerves. The patient's operation time, intraoperative blood loss, hospital stay time, and postoperative complications were recorded. Fracture healing and reduction were evaluated according to X-ray and CT after operation. Constant-Murley score and Rockwood sternoclavicular joint score were used to evaluate limb function at 12 months after operation. RESULTS: All the patients were treated with sternoclavicular hook-plate. The operation time ranged from 50 to 76 min, with a mean of (54.08±13.91) min. The intraoperative blood loss ranged from 20 to 56 ml, with a mean of (46.08±11.15) ml. The hospital stay time ranged from 6 to 14 d, with a mean of (8.31±2.32) d. X-ray and CT examination on the second day after operation showed that all fractures and dislocations were anatomically reduced, and shoulder joint function exercise was performed early. All patients were followed up, and the duration ranged from 12 to 24 months, with a mean of (16.77±4.63) months. The healing time ranged from 9 to 13 d, with a mean of (11.00±1.75) d;and the bone healing time ranged from 3 to 4 months, with a mean of (3.65±0.46) months. There were no complications such as infection, internal fixation failure and nerve injury. At 12 months follow-up, the constant Murley score ranged from 78 to 100, with a mean of 87.83± 11.26; and Rockwood score ranged from 9 to 15, with a mean of 13.70±1.85. Among them, 11 cases were excellent, 1 case was good, and 1 case was general. CONCLUSION: The use of the novel sternoclavicular hook-plate for treatment of proximal clavicle fracture with dislocation of sternoclavicular joint is an effectively internal fixation with high safety, allowing early functional exercise for patients.

Effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells.

Cryopreservation is widely used in regenerative medicine for tissue preservation. In the present study, the effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells (HUVECs) were investigated. After 0, 4, 8, 12 or 24 weeks of cryopreservation in liquid nitrogen, the HUVECs were thawed. The excretory functions markers (endothelin­1, prostaglandin E1, von Willebrand factor and nitric oxide) of HUVECs were measured by ELISA assay. The expression of intercellular adhesion molecule­1 (ICAM­1) in HUVECs was analyzed using flow cytometry. An angiogenesis assay was used to determine the angiogeneic capabilities of the thawed HUVECs. The results demonstrated that cryopreserved/thawed and recultivated HUVECs were unsuitable for tissue­engineered microvascular construction. Specifically, the excretory function of the cells was significantly decreased in the post­cryopreserved HUVECs at 24 weeks. In addition, the level of ICAM­1 in HUVECs was significantly upregulated from the fourth week of cryopreservation. Furthermore, the tube­like structure­forming potential was weakened with increasing cryopreservation duration, and the numbers of lumen and the length of the pipeline were decreased in the thawed HUVECs, in a time­dependent manner. In conclusion, the results of the present study revealed that prolonged cryopreservation may lead to HUVEC dysfunction and did not create stable cell lines for tissue­engineered microvascular construction.

The invention of an iliosacral screw fixation guide and its preliminary clinical application.

OBJECTIVE: To introduce an iliosacral screw fixation guide and evaluate its efficacy in fixation of sacroiliac joint fracture-dislocations. METHODS: Between January 2011 and May 2011, eight patients (five men, three women) with sacroiliac joint fracture-dislocation underwent percutaneous iliosacral screw fixation with the assistance of this minimally invasive guide and under CT guidance. The patients, aged from 26 to 56 years (mean 32 years), had vertically unstable pelvic fractures. Before surgery, six patients who had displacement of >2 cm in their sacroiliac joints underwent skeletal traction on the femoral condyle. The inserted sites were marked out on the affected side of their buttocks after the best screw trajectory had been determined under CT control. The gear that controls the direction of the minimally invasive guide was adjusted according to the inserting angle determined by CT scans. A K-wire was inserted into the sacroiliac joint along the pilot sleeve of the guide, and a hollow screw (diameter 7.3 mm) was implanted into the sacroiliac joint along the K-wire. RESULTS: All eight operations were successful on the first attempt. The operations lasted from 10 to 20 minutes (mean 14 minutes). Immediate CT scans confirmed that all the screws had been placed in the desired positions, none had penetrated the bones and the configuration of the sacroiliac joints had been satisfactorily restored and firmly fixed. No patient experienced numbness or radiating pain in the lower limbs during surgery. There were no postoperative vascular or neurological complications. CONCLUSION: The minimally invasive guide can eliminate discrepancies resulting from the surgeon's own sensory input when inserting screws under the guidance of CT, making percutaneous iliosacral screw fixation more accurate, safe and simple.

Protective effects of erythropoietin in experimental spinal cord injury by reducing the C/EBP-homologous protein expression.

OBJECTIVES: Erythropoietin (EPO) is a variety of tissue-protective functions, including spinal cord. This study aimed to determine the neuron protective effect of erythropoietin on spinal cord injury (SCI) by assessing C/EBP-homologous protein (CHOP) in the development of a rat model of SCI. METHODS: Sixty Sprague-Dawley rats were randomly assigned to three groups: sham-operation control group, SCI group, and EPO treatment group. By using a weight-drop contusion SCI model, the rats in the SCI group and EPO treatment group were killed at 1 and 7 days subsequently. The Basso, Beattie, and Bresnahan (BBB) scores were examined for locomotor function. Pathological changes were observed after hematoxylin-eosin (H&E) staining. The expression of CHOP was determined by immunohistochemical staining and RT-PCR analysis. RESULTS: BBB scores showed more quick recovery in the erythropoietin treatment group than that in the SCI group (P < 0.01). Pathological changes also revealed a reduction in the volume of cavitations and more neurons regeneration in the EPO treatment rats than that of the SCI rats. The number of CHOP positive cells in the SCI group on day 1 and 7 days after SCI increased compared with the erythropoietin treatment group and sham-operation control group (P < 0.01). CHOP mRNA folds in sham-operation control rat from 1 to 7 days showed the same trend. CONCLUSIONS: Endoplasmic reticulum (ER) stress was triggered at the early stage of SCI. Increased expression of CHOP can be found in the injured segment of the spinal cord after injury. EPO treatment could prevent pathological alterations from severe spinal cord injury by reducing expression of CHOP.

[Analysis of delayed diagnosis of the vertical unstable pelvic fractures].

OBJECTIVE: To explore the causes of delayed diagnosis of the vertical unstable pelvic fractures in patients with multiple trauma so in order to minimize these incidence. METHODS: A retrospective study was conducted in 176 patients with the vertical unstable pelvic fractures from January 2003 to December 2008. The classification of vertical unstable pelvic fractures was recorded. Medical data were compared and statistically analyzed to identify the incidence, and the contributing factors of the delayed diagnosis of the vertical unstable pelvic fractures. Of the 176 patients, 46 (26.1%) had delayed diagnosis of the vertical unstable pelvic fractures. There were 29 males and 17 females with an average age of 34 years old. RESULTS: Of the factors contributing to 46 cases of delayed diagnosis, 41.3% (19/46) closely related to the evaluation by the doctors and were potentially avoidable, and 58.7% (27/46) were associated with the severity of the injuries. CONCLUSION: The patients with multiple trauma had high incidence of delayed diagnosis of the vertical unstable pelvic fractures. The recognition of pelvic fractures, careful clinical assessments, and the awareness of the orthopedic doctors, emergency doctors and ICU doctors. Most of the delayed diagnosis of the vertical unstable pelvic fractures in patients with multiple trauma are potentially avoidable.

Investigation of the protective effect of erythropoietin on spinal cord injury in rats.

Erythropoietin (EPO) is a promising therapeutic agent used in a variety of spinal cord injuries. Therefore, identifying the specific molecular pathway mediating the neuronal protective effect of EPO after spinal cord injury (SCI) is of great value to the patients concerned. Platelet-derived growth factor (PDGF)-B is an important factor in the recovery of neurological function. We explored changes in the expression of PDGF-B in spinal cord injury rats after receiving EPO treatment. We used a weight-drop contusion SCI model, and EPO treatment group rats received single doses of EPO (1,000 U/kg i.p.) immediately after the operation. Seven days after the operation, the results revealed a more rapid recovery as noted by the higher BBB scores, less disruption and more neuronal regeneration of the spinal cord in the EPO treatment group than that in the SCI group. PDGF-B expression also increased in the EPO treatment group compared to that in the SCI group (P<0.01). This study showed that PDGF-B plays a role in the neuronal protective effect of EPO on spinal cord injury in rats, which may help to explain the quick recovery after EPO treatment of spinal cord injury.

TSP-1 expression changes in diabetic rats with spinal cord injury.

OBJECTIVES: Spinal cord injury (SCI) is associated with high morbidity and mortality worldwide, especially in patients with diabetes mellitus. Thrombospondin 1 (TSP-1) is a mutual activator and can cause neuron injury during hyperglycemia. We investigated the role of TSP-1 in a model of diabetic rats in the development of SCI. METHODS: Thirty Sprague-Dawley female rats were divided into three groups (SCI group, SCI + diabetes group and sham-operated group) at random. Ten rats were intraperitoneally injected with streptozocin (60 mg/kg) to induce diabetes; the remaining 20 rats received an injection of 0.9% saline as SCI group and the third group was sham-operated group. Four weeks later, ten rats in the SCI group and ten diabetic rats were subjected to SCI using an impactor, and the sham-operated group was also followed at the same time course without SCI. These animals were killed at 12 hours after SCI for immunochemistry and Western blot analysis of the injured section for the expression of TSP-1 protein. Morphological changes of spinal cord in three groups also were observed through hematoxylin-eosin staining. All data were analysed by t-test. RESULTS: The data of weight and blood sugar indicated no significant difference in all three groups before animal model induction. Four weeks after the induction of diabetes, the differences between the SCI and SCI + diabetes groups in weight and blood sugar were distinct. Immunochemistry and Western blot analysis showed increased TSP-1 expression in SCI group when compared with the sham-operated group rat but less than the SCI + diabetes group (p<0.01). The pathological alterations, such as central core lesion with a spare peripheral rim of tissue, and variable cyst formations and gliosis were very apparent in the damaged spinal cord area in the SCI group and especially in the SCI + diabetes group. DISCUSSION: Our work provides experimental evidence that the elevated expression of TSP-1 can be detected in the injured segment of the spinal cord at 12 hours after injury in diabetic rats. It may contribute to severe damage in diabetic rats after SCI.

[An anatomic study of lag screw placement in anterior column of acetabulum and design of targeting device].

OBJECTIVE: To provide the anatomic basis for the lag screw placement in the anterior column of the acetabulum. METHODS: Twenty-two pelvis specimens with 44 acetabula of the native adult cadavers were studied. The anthropometric measurement was performed on 44 acetabula to determine the shape of the transverse section of the anterior column of the acetabulum, the optimal entry point for the lag screw on the outer table of the ilium, the direction of the screw, and the distance from the entry point to the obturator groove. RESULTS: The transverse section of the anterior column of the acetabulum was almost triangle-shaped. The path for the lag screw placement was 10.5 +/- 0.8 mm in diameter. The optimal entry point on the posterolateral ilium for the screw fixation was found to exist 9.2 +/- 2.4 mm superior to the line between the anterior superior iliac spine and the greater sciatic notch and 38.5 +/- 3.8 mm superior to the greater sciatic notch. The distance from the entry point to the obturator groove was 84.1 +/- 6.2 mm. The inclination of the lag screw was 54.2 +/- 5.5 degrees at the caudal direction in the sagittal plane and 40.7 +/- 3.8 degrees in the horizontal plane. The device for the safe screw placement in the anterior column was designed. CONCLUSION: The above data can facilitate an insertion of one 6.5 mm lag screw into the anterior acetabular column and minimize the risk of articular violation or cortical penetration, which has a narrow margin of safety. The safe length of the lag screw should be 70 mm. The optimal entry point on the posterolateral ilium for the screw fixation is determined to be 10 mm superior to the line between the anterior superior iliac spine and the greater sciatic notch and 40 mm superior to the greater sciatic notch. The inclination of the lag screw should be 55 degrees at the caudal direction in the sagittal plane and 40 degrees in the horizontal plane. It is safe to place the lag screw in the anterior column with the help of the targeting device.

An anatomical study of corona mortis and its clinical significance.

OBJECTIVE: To provide detailed information of corona mortis for ilioinguinal approach as an anterior approach to the acetabulum and pelvis. METHODS: The course, branches and distribution of the vascular connection between the obturator system and the external iliac or inferior epigastric systems located over the superior pubic ramus were observed on 50 hemipelvises with intact soft tissues. RESULTS: During the dissections, 72% of the cadaveric sides had at least one communicating vessel between the obturator system and the external iliac or inferior epigastric systems on the superior pubic ramus. The average diameter of the connecting vessel was 2.6 mm (range, 2.0-4.2 mm). It coursed over the superior pubic ramus or iliopubic eminence vertically to enter the obturator foramen and exit the pelvis. The average distance from pubic symphysis to the vascular connections between the obturator and external iliac systems was 52 mm (range, 38-68 mm). CONCLUSIONS: Vascular connections between the obturator system and the external iliac or inferior epigastric systems were found over the superior pubic ramus with a high incidence. They are prone to damage during the ilioinguinal approach as an anterior approach to the acetabulum and pelvis. Thus, corona mortis located over the superior pubic ramus deserves great attention during the ilioinguinal approach.