[Effectiveness of bone transport with a locking plate versus conventional bone transport for tibial defects].

Objective: To investigate the effectiveness difference between bone transport with a locking plate (BTLP) and conventional bone transport with Ilizarov/Orthofix fixators in treatment of tibial defect. Methods: The clinical data of 60 patients with tibial fractures who met the selection criteria between January 2016 and September 2020 were retrospectively analyzed, and patients were treated with BTLP (BTLP group, n=20), Ilizarov fixator (Ilizarov group, n=23), or Orthofix fixator (Orthofix group, n=17) for bone transport. There was no significant difference in gender, age, cause of injury, time from injury to admission, length of bone defect, tibial fracture typing, and comorbidities between groups ( P>0.05). The osteotomy time, the retention time of external fixator, the external fixation index, and the occurrence of postoperative complications were recorded and compared between groups. The bone healing and functional recovery were evaluated by the Association for the Study and Application of the Method of Ilizarov (ASAMI) criteria. Results: All patients of 3 groups were followed up 13-45 months, with a mean of 20.4 months. The osteotomy time was significantly shorter in the BTLP group than in the Ilizarov group, and the retention time of external fixator and the external fixation index were significantly lower in the BTLP group than in the Ilizarov and Orthofix groups ( P<0.05). Twenty-two fractures healed in the Ilizarov group and 1 case of delayed healing; 16 fractures healed in the Orthofix group and 1 case of delayed healing; 18 fractures healed in the BTLP group and 2 cases of delayed healing. There was no significant difference between groups in fracture healing distribution ( P=0.824). After completing bone reconstruction treatment according to ASAMI criteria, the BTLP group had better bone healing than the Orthofix group and better function than the Ilizarov groups, showing significant differences ( P<0.05). Postoperative complications occurred in 4 cases (20%) in the BLTP group, 18 cases (78%) in the Ilizarov group, and 12 cases (70%) in the Orthofix group. The incidence of complication in the BTLP group was significantly lower than that in other groups ( P<0.05). Conclusion: BTLP is safe and effective in the treatment of tibial defects. BTLP has apparent advantages over the conventional bone transport technique in osteotomy time, external fixation index, and lower limb functional recovery.

ß-Ecdysterone Enhanced Bone Regeneration Through the BMP-2/SMAD/RUNX2/Osterix Signaling Pathway.

Bone defects are a global public health problem. However, the available methods for inducing bone regeneration are limited. The application of traditional Chinese herbs for bone regeneration has gained popularity in recent years. ß-ecdysterone is a plant sterol similar to estrogen, that promotes protein synthesis in cells; however, its function in bone regeneration remains unclear. In this study, we investigated the function of ß-ecdysterone on osteoblast differentiation and bone regeneration in vitro and in vivo. MC3T3-E1 cells were used to test the function of ß-ecdysterone on osteoblast differentiation and bone regeneration in vitro. The results of the Cell Counting Kit-8 assay suggested that the proliferation of MC3T3-E1 cells was promoted by ß-ecdysterone. Furthermore, ß-ecdysterone influenced the expression of osteogenesis-related genes, and the bone regeneration capacity of MC3T3-E1 cells was detected by polymerase chain reaction, the alkaline phosphatase (ALP) test, and the alizarin red test. ß-ecdysterone could upregulate the expression of osteoblastic-related genes, and promoted ALP activity and the formation of calcium nodules. We also determined that ß-ecdysterone increased the mRNA and protein levels of components of the BMP-2/Smad/Runx2/Osterix pathway. DNA sequencing further confirmed these target effects. ß-ecdysterone promoted bone formation by enhancing gene expression of the BMP-2/Smad/Runx2/Osterix signaling pathway and by enrichment biological processes. For in vivo experiments, a femoral condyle defect model was constructed by drilling a bone defect measuring 3 mm in diameter and 4 mm in depth in the femoral condyle of 8-week-old Sprague Dawley male rats. This model was used to further assess the bone regenerative functions of ß-ecdysterone. The results of micro-computed tomography showed that ß-ecdysterone could accelerate bone regeneration, exhibiting higher bone volume, bone surface, and bone mineral density at each observation time point. Immunohistochemistry confirmed that the ß-ecdysterone also increased the expression of collagen, osteocalcin, and bone morphogenetic protein-2 in the experiment group at 4 and 8 weeks. In conclusion, ß-ecdysterone is a new bone regeneration regulator that can stimulate MC3T3-E1 cell proliferation and induce bone regeneration through the BMP-2/Smad/Runx2/Osterix pathway. This newly discovered function of ß-ecdysterone has revealed a new direction of osteogenic differentiation and has provided novel therapeutic strategies for treating bone defects.

Shear-responsive boundary-lubricated hydrogels attenuate osteoarthritis.

Lipid-based boundary layers formed on liposome-containing hydrogels can facilitate lubrication. However, these boundary layers can be damaged by shear, resulting in decreased lubrication. Here, a shear-responsive boundary-lubricated drug-loaded hydrogel is created by incorporating celecoxib (CLX)-loaded liposomes within dynamic covalent bond-based hyaluronic acid (HA) hydrogels (CLX@Lipo@HA-gel). The dynamic cross-linked network enables the hydrogel to get restructured in response to shear, and the HA matrix allows the accumulation of internal liposome microreservoirs on the sliding surfaces, which results in the formation of boundary layers to provide stable lubrication. Moreover, hydration shells formed surrounding the hydrogel can retard the degradation process, thus helping in sustaining lubrication. Furthermore, in vitro and in vivo experiments found that CLX@Lipo@HA-gels can maintain anabolic-catabolic balance, alleviate cartilage wear, and attenuate osteoarthritis progression by delivering CLX and shear-responsive boundary lubrication. Overall, CLX@Lipo@HA-gels can serve as shear-responsive boundary lubricants and drug-delivery vehicles to alleviate friction-related diseases like osteoarthritis.

Connexin 43 affects thoracic ossification of ligamentum flavum by regulating the p38 MAPK-RUNX2 signaling pathway.

This study aimed to investigate the role of connexin 43 (CX43) in thoracic ossification of ligamentum flavum (TOLF) based on the p38 mitogen-activated protein kinase (p38MAPK)-runt-related transcription factor 2 (RUNX2) pathway. Immunohistochemistry was used to detect CX43 expression in TOLF and non-TOLF patients, fibroblasts of TOLF were isolated and induced osteogenic differentiation, and CX43 expression was detected by western blot analysis (WB). In addition, si-CX43 was used to intervene CX43, and SB203580 was used to inhibit the p38MAPK. The expressions of bone differentiation marker protein were detected by WB, and the ossification ability was analyzed by alizarin red staining. The interaction between RUNX2 and CX43 was identified by dual-luciferase reporter assay. Results found that CX43 was highly expressed during TOLF, and si-CX43 could inhibit the expression of alkaline phosphatase (ALP) and osteopontin (OPN), as well as inhibit TOLF and the p38MAPK-RUNX2 pathway. In addition, SB203580 showed a synergistic effect with si-CX43 to further inhibit TOLF and the expression of RUNX2. The dual-luciferase reporter assay confirmed that RUNX2 could bind to the CX43 promoter. In conclusion, CX43 promotes TOLF, which may be mediated by p38MAPK-RUNX2, and RUNX2 binds to the CX43 promoter to form a positive feedback regulatory loop during TOLF.

Marein Prevented LPS-Induced Osteoclastogenesis by Regulating the NF-κB Pathway In Vitro.

Many bone diseases such as osteolysis, osteomyelitis, and septic arthritis are caused by gram-negative bacterial infection, and lipopolysaccharide (LPS), a bacterial product, plays an essential role in this process. Drugs that inhibit LPS-induced osteoclastogenesis are urgently needed to prevent bone destruction in infective bone diseases. Marein, a major bioactive compound of Coreopsis tinctoria, possesses anti-oxidative, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic, and anti-diabetic effects. In this study, we measured the effect of marein on RAW264.7 cells by CCK-8 assay and used TRAP staining to determine osteoclastogenesis. The levels of osteoclast-related genes and NF-κB-related proteins were then analyzed by western blot, and the levels of pro-inflammatory cytokines were quantified by ELISA. Our results showed that marein inhibited LPS-induced osteoclast formation by osteoclast precursor RAW264.7 cells. The effect of marein was related to its inhibitory function on expressions of pro-inflammatory cytokines and osteoclast-related genes containing RANK, TRAF6, MMP-9, CK, and CAII. Additionally, marein leads to markedly inhibited NF-κB signaling pathway activation in LPS-induced RAW264.7 cells. Concurrently, when the NF-κB signaling pathway was inhibited, osteoclast formation and pro-inflammatory cytokine expression were decreased. Collectively, marein could inhibit LPS-induced osteoclast formation in RAW264.7 cells via regulating the NF-κB signaling pathway. Our data demonstrate that marein might be a potential drug for bacteria-induced bone destruction disease. Our findings provide new insights into LPS-induced bone disease.

[Comparison of effectiveness of femoral neck system and cannulate compression screw in treatment of femoral neck fracture in young and middle-aged patients].

OBJECTIVE: To compare the effectiveness of femoral neck system (FNS) and cannulate compression screw (CCS) in the treatment of femoral neck fractures in young and middle-aged patients. METHODS: The clinical data of 82 young and middle-aged patients with femoral neck fracture treated between January 2018 and September 2020 were retrospectively analyzed. They were divided into FNS group (24 cases) and CCS group (58 cases) according to different surgical methods. There was no significant difference between the two groups ( P>0.05) in general data such as gender, age, height, body mass, cause of injury, complications, fracture location, and fracture classification (Garden classification and Pauwells classification). The operation time, intraoperative blood loss, complications (nonunion, osteonecrosis of the femoral head, shortening of femoral neck, etc.), visual analogue scale (VAS) score at 2 days after operation, clinical healing time of fracture, and Harris score of hip joint after operation were recorded and compared between the two groups. RESULTS: The operation time and VAS score at 2 days after operation in FNS group were significantly lower than those in CCS group ( P<0.05); there was no significant difference in intraoperative blood loss between the two groups ( t=0.263, P=0.796). The patients in CCS group were followed up 6-18 months, with an average of 13.6 months; and the follow-up time in FNS group was 3-12 months, with an average of 7.3 months. There was no complication of internal fixator loosening in both groups. There were 2 cases of osteonecrosis of the femoral head, 1 case of bone nonunion, and 13 cases of femoral neck shortening in CCS group and only 2 cases of femoral neck shortening in FNS group. The difference in the incidence of complications between the two groups (27.6% vs. 8.3%) was significant ( χ 2=36.670, P=0.015). In CCS group, 3 cases underwent secondary artificial hip arthroplasty due to bone nonunion and osteonecrosis of the femoral head, and the remaining 55 cases achieved clinical healing; in FNS group, 6 patients excluded in the statistics because the follow-up time was less than 6 months, and the remaining 18 fractures healed clinically; there was significant difference in fracture healing time between the two groups ( t=4.481, P=0.000). The difference of Harris score of hip joint between 9 months and 6 months after operation in FNS group was significantly higher than that in CCS group ( P<0.05), and the Harris score at 9 months after operation was significantly higher than that at 6 months after operation in both groups ( P<0.05). CONCLUSION: FNS can accelerate the healing of femoral neck fractures in young and middle-aged patients, so that patients can start functional exercise as soon as possible, thereby reducing the incidence of related complications.

Applications of Functionalized Hydrogels in the Regeneration of the Intervertebral Disc.

Intervertebral disc degeneration (IDD) is caused by genetics, aging, and environmental factors and is one of the leading causes of low back pain. The treatment of IDD presents many challenges. Hydrogels are biomaterials that possess properties similar to those of the natural extracellular matrix and have significant potential in the field of regenerative medicine. Hydrogels with various functional qualities have recently been used to repair and regenerate diseased intervertebral discs. Here, we review the mechanisms of intervertebral disc homeostasis and degeneration and then discuss the applications of hydrogel-mediated repair and intervertebral disc regeneration. The classification of artificial hydrogels and natural hydrogels is then briefly introduced, followed by an update on the development of functional hydrogels, which include noncellular therapeutic hydrogels, cellular therapeutic hydrogel scaffolds, responsive hydrogels, and multifunctional hydrogels. The challenges faced and future developments of the hydrogels used in IDD are discussed as they further promote their clinical translation.

[Study on the effect of qinggan jiangtang tablet in improving the insulin resistance in patients with multiple metabolic syndrome].

OBJECTIVE: To observe the effect of Qinggan Jiangtang tablet (QJT) in improving the insulin resistance (IR) in patients with multiple metabolic syndrome (MMS). METHODS: Adopting randomized controlled double-blinded method, 60 patients with MMS were divided equally into two groups. The treated group was treated by oral taking of QJT 3 tabs, twice a day and the control group treated by oral taking of Glucophage 3 tabs, twice a day, the therapeutic course for both groups was 1 month, and the observation lasted for 2 successive courses. RESULTS: After treatment, levels of blood glucose, fasting and postprandial blood glucose, C-peptide and IR were significantly reduced with markedly improvement of beta-cell function in both groups, the difference between the two groups showed no significance. Change of plasma level of free fatty acids before and after treatment in both groups was insignificant. CONCLUSION: QJT has the effects on reducing blood glucose, blood lipids, blood pressure and IR and improving function of beta cells.