The effect of Ding's screws and tension band wiring for treatment of olecranon fractures: a biomechanical study.

Although tension band wiring (TBW) is popular and recommended by the AO group, the high rate of complications such as skin irritation and migration of the K-wires cannot be ignored. Ding's screw tension band wiring (DSTBW) is a new TBW technique that has shown positive results in the treatment of other fracture types. The objective of this study was to evaluate the stability of DSTBW in the treatment of olecranon fractures by biomechanical testing. We conducted a Synbone biomechanical model by using three fixation methods: DSTBW, intramedullary screw and tension band wiring (IM-TBW), and K-wire TBW, were simulated to fix the olecranon fractures. We compared the mechanical stability of DSTBW, IM-TBW, and TBW in the Mayo Type IIA olecranon fracture Synbone model using a single cycle loading to failure protocol or pullout force. During biomechanical testing, the average fracture gap measurements were recorded at varying flexion angles in three different groups: TBW, IM-TBW, and DSTBW. The TBW group exhibited measurements of 0.982 mm, 0.380 mm, 0.613 mm, and 1.285 mm at flexion angles of 0°, 30°, 60°, and 90° respectively. The IM-TBW group displayed average fracture gap measurements of 0.953 mm, 0.366 mm, 0.588 mm, and 1.240 mm at each of the corresponding flexion angles. The DSTBW group showed average fracture gap measurements of 0.933 mm, 0.358 mm, 0.543 mm, and 1.106 mm at the same flexion angles. No specimen failed in each group during the cyclic loading phase. Compared with the IM-TBW and TBW groups, the DSTBW group showed significant differences in 60° and 90° flexion angles. The mean maximum failure load was 1229.1 ± 110.0 N in the DSTBW group, 990.3 ± 40.7 N in the IM-TBW group, and 833.1 ± 68.7 N in the TBW group. There was significant difference between each groups (p < 0.001).The average maximum pullout strength for TBW was measured at 57.6 ± 5.1 N, 480.3 ± 39.5 N for IM-TBW, and 1324.0 ± 43.8 N for DSTBW. The difference between maximum pullout strength of both methods was significant to p < 0.0001. DSTBW fixation provides more stability than IM-TBW and TBW fixation models for olecranon fractures.

HIF-1α regulates DcR3 to promote the development of endometriosis.

OBJECTIVE: The aim of this study was to investigate the expression and clinical significance of HIF-1α and DcR3 in endometriosis by analysing clinical case data. Tissue samples were collected for tissue chip analysis and staining, and human endometrial stromal cells were isolated and cultured for cell experiments. Additionally, experiments were conducted on collected peritoneal fluid to explore the association and role of HIF-1α and DcR3 in endometriosis. STUDY DESIGN: Patients who visited the Department of Obstetrics and Gynaecology at Central Hospital in Fengxian District, Shanghai, from January 2018 to December 2021 were recruited for this controlled study. Clinical data and tissue chip staining results were collected for multiple regression analysis on the clinical significance of HIF-1α and DcR3. Endometrial tissue, ovarian cysts, and pelvic fluid were collected, and human endometrial stromal cells were cultured. The impact of HIF-1α on DcR3 in different oxygen environments and its role in endometriosis were investigated through PCR, Western blotting, enzyme-linked immunosorbent assay, as well as adhesion and migration assays. RESULTS: In patients with endometriosis, the expression of DcR3 and HIF-1α was found to be upregulated and correlated in ectopic endometrium. The expression of DcR3 served as an indicator of the severity of endometriosis. Hypoxia induced the expression of DcR3, which was regulated by HIF-1α and promoted migration and adhesion. CONCLUSION: DcR3 can be used as a clinical indicator to assess the severity of endometriosis. The hypoxic environment in endometriosis enhances disease progression by regulating DcR3 through HIF-1α.

A novel technique of a new cannulated screw for treatment of inferior pole patellar fractures: a finite element study.

OBJECTIVE: We invented a new cannulated screw with holes on the tail, which called Ding's screw. The goal of this study was to evaluate the biomechanical outcomes of this new screw with tension band wiring for the treatment of inferior pole patellar fractures in a finite element model. METHODS: We conducted a finite element biomechanical study using two fixation methods: Ding's screw and tension band wiring (DSTBW) and cannulated screws and tension band wiring (CSTBW). Two methods were simulated to fix the inferior pole patellar fracture in a finite element model. The relative displacement and stress distribution were analyzed and compared. RESULT: There were less displacement and stress distribution of DSTBW in different knee movement (30°, 60°, 90°, 120°) when compared to CSTBW. The highest value of displacement of the fracture and von Mises stress of the internal fixation happened in 120° knee movement in both groups. The highest displacement of the DSTBW was less than that of the CSTBW (1.92 mm to 2.12 mm). The highest value of the stress on the screws was 110.60 MPa in DSTBW group, and 132.90 MPa in CSTBW group. The highest value of the stress on the titanium cable was 38.51 MPa in DSTBW group, and 41.91 MPa in CSTBW group. CONCLUSION: DSTBW fixation provides more stability than CSTBW fixation model in a finite element study.

Identification and validation of FPR1, FPR2, IL17RA and TLR7 as immunogenic cell death related genes in osteoarthritis.

Immunogenic cell death (ICDs) has gained increasing attention for its significant clinical efficacy in various diseases. Similarly, more and more attention has been paid in the role of immune factors in the pathological process of osteoarthritis (OA). The objective of this study is to reveal the relationship between ICD-related genes and the process of OA at the gene level through bioinformatics analysis. In this study, Limma R package was applied to identify differentially expressed genes (DEG), and OA related module genes were determined by weighted gene co-expression network analysis. The ICD-related genes were extracted from a previous study. The module genes related to DEGs and ICD were overlapped. Then, hub genes were identified by a series of analyses using the Least absolute shrinkage and selection operator and random forest algorithm, the expression level and diagnostic value of hub genes were evaluated by Logistic regression. In addition, we used Spearman rank correlation analysis to clarify the relationship between hub genes and infiltrating immune cells and immune pathways. The expression levels of FPR1, FPR2, IL17RA, and TLR7 was verified in SD rat knee joint model of OA by immunohistochemistry. The expression levels of FPR1, FPR2, IL17RA, and TLR7 mRNA were detected in the IL-1ß induced rat chondrocytes in qPCR experiment in vitro. Four hub genes (FPR1, FPR2, IL17RA, and TLR7) were ultimately identified as OA biomarkers associated with ICD. And knockdown of TLR7 reversed collagen II and ADAMTS-5 degradation in IL-1ß-stimulated chondrocytes. This research may provide new immune related biomarkers for the diagnosis of OA and serve as a reference for disease treatment monitoring.

The effect of ding's screw and tension band wiring for treatment of olecranon fractures: a finite element study.

BACKGROUND: Tension band wiring (TBW) is a common surgical intervention for olecranon fractures. However, high rate of complications such as loss of reduction, skin irritation, and migration of the K-wires were reported up to 80%. Ding's screw tension band wiring (DSTBW) is a new TBW technique that has shown positive results in the treatment of other fracture types. The objective of this study was to evaluate the stability of DSTBW in the treatment of olecranon fractures by finite element analysis. METHOD: We used Ding's screw tension band fixation (DSTBW) and K-wire tension band fixation (TBW) to establish a finite element model to simulate and fix olecranon fractures. The stress distribution, opening angle, twisting angle, and pullout strength of K-wires or screws were analyzed and compared. RESULTS: The maximum von Mises stress was observed on the internal fixation for 90° elbow motion in both groups. The von Mises value of the screw in DSTBW was 241.2 MPa, and the von Mises value of k-wire in TBW was 405.0 MPa. Opening angle: TBW was 0.730° and DSTBW was 0.741° at 45° flexion; TBW was 0.679° and DSTBW was 0.693° at 90° flexion. Twisting angle: TBW was 0.146° and DSTBW was 0.180° at 45° flexion; TBW was 0.111° and DSTBW was 0.134° at 90° flexion. The pullout strength of DSTBW was significantly higher than that of TBW. Maximum pullout strength of Ding's screw was 2179.1 N, maximum pullout strength of K-wire was 263.6 N. CONCLUSION: DSTBW technology provides stable fixation for olecranon fractures, reducing the risk of internal fixation migration and failure.

The effect of Ding's screws and tension band wiring for treatment of inferior pole patellar fractures.

OBJECTIVES: We developed a cannulated screw with holes in the tail, named the Ding's screw. The objective of this study was to evaluate the clinical effect of Ding's screw in the treatment of inferior pole patellar fracture. METHODS: From March 2017 to October 2021, 68 patients with inferior pole patellar fracture in our department were retrospectively reviewed. According to different treatment methods, they were divided into Ding's screw and tension band wiring group (DSTBW) and cannulated screws and tension band wiring group (CSTBW). Radiological and clinical outcomes were evaluated and compared. RESULTS: There were 33 cases in DSTBW group and 35 cases in CSTBW group. The mean follow-up duration was 14.5 ± 2.6 months in the DSTBW group and 15.0 ± 2.3 months in the CSTBW group. No significant differences in age, sex, operative side or time to surgery were present between the two groups. Skin breakdown and infection were not significantly different among the groups (P > 0.05). At the last follow-up, the average Bostman score of the DSTBW group was 28.5 ± 1.3(excellent) and that of the CSTBW group was 27.8 ± 1.6(good), with statistical significance (P = 0.045). The average Lysholm score of the DSTBW group was 94.1 ± 3.4 (good), and that of the CSTBW group was 90.1 ± 4.4 (good), and the difference was statistically significant (P < 0.001). The average knee joint ROM of the DSTBW group was 135.6 ± 6.8˚, and that of the CSTBW group was 130.1 ± 6.7˚, and the difference between the two groups was statistically significant (P = 0.001). CONCLUSIONS: DSTBW is an effective method for the treatment of inferior pole patellar fractures with stable fixation and good functional effect.

Minimally invasive technique of monoaxial percutaneous screws and instrumentational maneuvers in thoracolumbar and lumbar fractures.

OBJECTIVES: Percutaneous pedicle screw fixation (PPSF) has been a common surgery for treating thoracolumbar and lumbar fractures. Many studies have reported PPSF is associated with poor reduction. We present a reliable method by using short-segment monoaxial percutaneous screws and instrumentational maneuvers to reduce the spine. This study aimed to evaluate radiological and clinical results of this method of reduction compared to traditional polyaxial screws method in treating thoracolumbar and lumbar fractures. METHODS: From February 2015 to February 2021, 64 patients with thoracolumbar and lumbar fractures in our department were retrospectively reviewed and divided into experimental group and control group according to different treatment methods. The experimental group was treated with short-segment monoaxial percutaneous screws (which were inserted at the adjacent vertebrae one level above, one level below the fracture, and the fractured vertebra) and instrumentational maneuvers method, while the control group was treated with traditional polyaxial screws method. The operation time was recorded. Visual analogue scale (VAS) and Oswestry disability index (ODI) were assessed as the clinical outcomes. The anterior height of the injured vertebra (AVH), the kyphosis cobb angle and the vertebral wedge angle were used to evaluate the fracture radiological reduction. RESULTS: A total of 64 patients were enrolled including 31 in the experimental group and 33 in the control group. There were no significant difference in operation time, AVH, the kyphosis cobb angle,the wedge angle of injured vertebra,VAS and ODI score between the two groups in preoperation. In each group, there were significant differences in the AVH, the kyphosis cobb angle and wedge angle of injured vertebra between preoperation and immediate postoperation. In each group, there were significant differences in VAS and ODI score between the preoperation and last follow-up. The total correction rates of AVH,the kyphosis cobb angle and the wedge angle of injured vertebra were significantly higher in the experimental group than those in the control group, while the loss of correction was significantly lower than the control. CONCLUSIONS: The reduction technique using monoaxial percutaneous screws and instrumentational maneuvers for thoracolumbar and lumbar fractures exhibited better radiological results and satisfying functional outcomes when compared to traditional polyaxial screws.

Platelet-rich plasma enhances the repair capacity of muscle-derived mesenchymal stem cells to large humeral bone defect in rabbits.

Mesenchymal stem cell-based therapy is a highly attractive strategy that promotes bone tissue regeneration. The aim of the present study was to evaluate the combination effect of muscle-derived mesenchymal stem cells (M-MSCs) and platelet-rich plasma (PRP) on bone repair capacity in rabbits with large humeral bone defect. Precise cylindrical bone defects of 10 mm diameter and 5 mm depth were established in rabbit humeral bones, which were unable to be repaired under natural conditions. The rabbits received treatment with M-MSCs/PRP gel, M-MSCs gel, or PRP gel, or no treatment. The bone tissue regeneration was evaluated at day 0-90 after surgery by HE morphological staining, Lane-Sandhu histopathological scoring, tetracycline detection, Gomori staining and micro-computed tomography. Beyond that, Transwell assay, CCK8 assay, Western blot analysis and ALP activity detection were performed in M-MSCs in vitro with or without PRP application to detect the molecular effects of PRP on M-MSCs. We found that the repair effect of M-MSCs group or PRP group was limited and the bone defects were not completely closed at post-operation 90 d. In contrast, M-MSCs/PRP group received obvious filling in the bone defects with a Lane-Sandhu evaluation score of 9. Tetracycline-labeled new bone area in M-MSCs/PRP group and new mineralized bone area were significantly larger than that in other groups. Micro-computed tomography result of M-MSCs/PRP group displayed complete recovery of humeral bone at post-operation 90 d. Further in vitro experiment revealed that PRP significantly induced migration, enhanced the growth, and promoted the expression of Cbfa-1 and Coll I in M-MSCs. In conclusion, PRP application significantly enhanced the regeneration capacity of M-MSCs in large bone defect via promoting the migration and proliferation of M-MSCs, and also inducing the osteogenic differentiation.

MiR-135-5p promotes osteoblast differentiation by targeting HIF1AN in MC3T3-E1 cells.

BACKGROUND: MicroRNAs (miRNAs or miRs) serve crucial roles in the progression of osteoporosis. This study investigated the role and specific molecular mechanism of miR-135-5p in regulating osteoblast differentiation and calcification. METHODS: Bone morphogenetic protein 2 (BMP2) was employed to interfere with the differentiation of MC3T3-E1. Then, miR-135-5p mimic or miR-135-5p inhibitor was transfected into MC3T3-E1, and quantitative RT-PCR was used to measure the expression of miR-135-5p. The expressions of runt-related transcription factor 2 (Runx2), osterix (OSX), osteopontin (OPN), and osteocalcin (OCN) were determined using western blot. Alkaline phosphatase (ALP) activity was measured using an appropriate kit assay. Calcium nodule staining was evaluated with alizarin red staining. A luciferase reporter assay was used to verify the target of miR-135-5p. Hypoxia-inducible factor 1 α inhibitor (HIF1AN) overexpression was applied to investigate its own role in the mechanism and a miR-135-5p rescue experiment was also performed. RESULTS: Overexpression of miR-135-5p promoted osteogenic differentiation and calcification, as shown by the increase in ALP activity, calcification and osteogenic marker levels, including Runx2, OSX, OPN and OCN. Knockdown of miR-135-5p yielded the opposite results. HIF1AN was confirmed as a direct target of miR-135-5p. HIF1AN overexpression inhibited osteogenic differentiation and calcification while miR-135-5p reversed these effects. CONCLUSIONS: These results indicate that miR-135-5p might have a therapeutic application related to its promotion of bone formation through the targeting of HIF1AN.

New insights into mechanism of bisphenol analogue neurotoxicity: implications of inhibition of O-GlcNAcase activity in PC12 cells.

Bisphenol analogues including bisphenol A and its derivatives are ubiquitous environmental contaminants and have been linked to adverse neurodevelopment effects on animals and humans. Most toxicological research focused on estrogen receptor mediated pathways and did not comprehensively clarify the observed toxicity. O-GlcNAcase (OGA), the highest level in brain, plays a critical role in controlling neuronal functions at multi-levels from molecule to animal behaviors. In this work, we intend to investigate the underlying molecular mechanisms for the neurotoxicity of bisphenol analogues by identifying their cellular targets and the resultant effects. The inhibitory actions of seven bisphenol analogues on the OGA activity at molecular level were investigated by our developed electrochemical biosensor. We found that their potency varied with substituent groups, in which tetrabromo bisphenol A (TBBPA) was the strongest. The seven bisphenol analogues (0-100 µM exposure) significantly inhibited OGA activity and up-regulated protein O-GlcNAcylation level in PC12 cells. Inhibition of OGA by bisphenol analogues further induced intracellular calcium, ROS, inflammation, repressed proliferation, interfered with cell cycle, induced apoptosis. And especially, 10 µM tetrabromo bisphenol A (TBBPA) exposure could impair the growth and development of neurite in human neural stem cells (hNSCs). Molecular docking for OGA/bisphenol analogue complexes revealed the hydrophobicity-dominated inhibition potency. OGA, as a new cellular target of bisphenol analogues, would illuminate the molecular mechanism of bisphenol analogues neurotoxicity.

Enhancing the Astrocytic Clearance of Extracellular α-Synuclein Aggregates by Ginkgolides Attenuates Neural Cell Injury.

The accumulation of aggregated forms of the α-Synuclein (α-Syn) is associated with the pathogenesis of Parkinson's disease (PD), and the efficient clearance of aggregated α-Syn represents a potential approach in PD therapy. Astrocytes are the most numerous glia cells in the brain and play an essential role in supporting brain functions in PD state. In the present study, we demonstrated that cultured primary astrocytes engulfed and degraded extracellular aggregated recombinant human α-Syn. Meanwhile, we observed that the clearance of α-Syn by astrocytes was abolished by proteasome inhibitor MG132 and autophagy inhibitor 3-methyladenine (3MA). We further showed that intracellular α-Syn was reduced after ginkgolide B (GB) and bilobalide (BB) treatment, and the decrease was reversed by MG132 and 3MA. More importantly, GB and BB reduced indirect neurotoxicity to neurons induced by α-Syn-stimulated astrocytic conditioned medium. Together, we firstly find that astrocytes can engulf and degrade α-Syn aggregates via the proteasome and autophagy pathways, and further show that GB and BB enhance astrocytic clearance of α-Syn, which gives us an insight into the novel therapy for PD in future.

Bisphenol F Disrupts Thyroid Hormone Signaling and Postembryonic Development in Xenopus laevis.

The safety of bisphenol A (BPA) alternatives has attracted much attention due to their wide use. In this study, we investigated the effects of bisphenol F (BPF), an alternative to BPA, on thyroid hormone (TH) signaling and postembryonic development in vertebrates using T3-induced and spontaneous Xenopus metamorphosis as models. We found that in the T3-induced metamorphosis assay, higher concentrations of BPF (100-10000 nM) antagonized T3-induced TH-response gene transcription and morphological changes including intestinal remodeling in a concentration-dependent manner, whereas 10 nM BPF exerted stimulatory effects on T3-induced integral metamorphosis when inhibited T3-induced TH-response gene transcription, demonstrating TH signaling disrupting effects of BPF. In the spontaneous metamorphosis assay, correspondingly, BPF inhibited development at metamorphic climax (with high endogenous TH levels), but promoted pre- and pro-metamorphic development (with low endogenous TH levels), displaying a developmental stage-dependent manner. Importantly, we observed agonistic actions of BPF on Notch signaling in intestines, showing that BPF disrupts vertebrate development possibly via multi pathways besides TH signaling. Thus, we infer the biphasic concentration-response relationship between BPF exposure and T3-induced metamorphosis could result from the interactions of TH signaling with other signaling pathways such as Notch signaling. Our study highlights the adverse influences of BPF on vertebrate development.

Ginkgolide B and bilobalide ameliorate neural cell apoptosis in α-synuclein aggregates.

The accumulation of aggregated forms of the α-Synuclein (α-Syn) is associated with the pathogenesis of Parkinson's disease (PD), a chronic progressive neurodegenerative disorder. Extensive evidences have shown the promising effects of Ginkgo biloba consumption on motor activity after PD. However, the mechanisms underline the α-Syn-induced cell damage and whether ginkgolides exert neuroprotection against this injury are unclear. Here we showed that aggregated recombinant human α-Syn, but not α-Syn monomers, triggered cell injury in cultured human neuroblastoma cell line SH-SY5Y in an apoptosis way by using flow cytometry and western blot assay. Moreover, pre-treatment with the Ginkgolide B (GB) or Bilobalide (BB) protected SH-SY5Y cells against α-Syn-induced cell viability decreases, and reduced cell apoptosis after aggregated α-Syn stimulation. Together, we firstly find that aggregated α-Syn induced cell apoptosis and GB and BB may attenuate aggregated α-Syn-induced cell apoptosis, which gives us an insight into the novel therapy for PD in future.

Atp13a2 Deficiency Aggravates Astrocyte-Mediated Neuroinflammation via NLRP3 Inflammasome Activation.

AIM: Atp13a2 (Park9) gene encodes a transmembrane lysosomal P5-type ATPase (ATP13A2), and its missense or truncation mutations leads to lysosomal dysfunction and consequently results in neuronal death in the pathogenesis of Parkinson's disease (PD). Nevertheless, the roles of ATP13A2 in the biological features of astrocytes, especially in the regulation of PD-related neuroinflammation, have not been investigated. METHODS: We cultured primary neurons and astrocytes from mouse midbrain to investigate the mechanisms for astrocyte ATP13A2-regulated lysosomal function and neuroinflammation following 1-methyl-4-phenylpyridinium (MPP(+) ) treatment. RESULTS: We found that astrocytes expressed considerable levels of ATP13A2 and deficiency of ATP13A2 in astrocyte-induced intense inflammation, which exacerbated dopaminergic neuron damage after exposure to MPP(+) . Notably, lack of ATP13A2 increased lysosomal membrane permeabilization and cathepsin B release, which in turn exacerbated activation of nod-like receptor protein 3 (NLRP3) inflammasome to produce excess IL-1ß from astrocytes. Furthermore, overexpression of ATP13A2 reversed MPP(+) -induced cathepsin B release and NLRP3 inflammasome activation in astrocytes. CONCLUSIONS: Our results have revealed a novel role of ATP13A2 in modulating astrocyte-mediated neuroinflammation via NLRP3 inflammasome activation, thus bringing to light of a direct link between astrocyte lysosome and neuroinflammation in the pathological model of PD.

Characterization of Three Tetrabromobisphenol-S Derivatives in Mollusks from Chinese Bohai Sea: A Strategy for Novel Brominated Contaminants Identification.

Identification of novel brominated contaminants in the environment, especially the derivatives and byproducts of brominated flame retardants (BFRs), has become a wide concern because of their adverse effects on human health. Herein, we qualitatively and quantitatively identified three byproducts of tetrabromobisphenol-S bis(2,3-dibromopropyl ether) (TBBPS-BDBPE), including TBBPS mono(allyl ether) (TBBPS-MAE), TBBPS mono(2-bromoallyl ether) (TBBPS-MBAE) and TBBPS mono(2,3-dibromopropyl ether) (TBBPS-MDBPE) as novel brominated contaminants. Meanwhile, the mass spectra and analytical method for determination of TBBPS-BDBPE byproducts were presented for the first time. The detectable concentrations (dry weight) of TBBPS-MAE, TBBPS-MBAE and TBBPS-MDBPE were in the ranges 28-394 µg/g in technical TBBPS-BDBPE and 0.1-4.1 ng/g in mollusks collected from the Chinese Bohai Sea. The detection frequencies in mollusk samples were 5%, 39%, 95% for TBBPS-MAE, TBBPS-MBAE and TBBPS-MDBPE, respectively, indicating their prevailing in the environment. The results showed that they could be co-produced and leaked into the environment with production process, and might be more bioaccumulative and toxic than TBBPS-BDBPE. Therefore, the production and use of TBBPS derivatives lead to unexpected contamination to the surrounding environment. This study also provided an effective approach for identification of novel contaminants in the environment with synthesized standards and Orbitrap high resolution mass spectrometry.