Osteoarthritis (OA) is the predominant cause of disability among elderly people worldwide and is characterized by cartilage degeneration and excessive bone formation. Phillyrin, derived from forsythia, is a key extract renowned for its pronounced antibacterial and anti-inflammatory effects. Forsythia, deeply integrated into traditional Oriental medicine, has historically been utilized for its various pharmacological effects, including antibacterial, anti-inflammatory, and hepato-protective properties. Nevertheless, the anti-inflammatory impact of phillyrin on the progression of osteoarthritis remains enigmatic. The objective of this research was to assess the anti-inflammatory and anti-aging properties of phillyrin in mouse chondrocytes induced by IL-1β, as well as to elucidate the fundamental mechanisms underlying the phenomenon at play. Additionally, the investigation extends to observing the impact of phillyrin by establishing a murine osteoarthritic model. The ultimate goal was to identify phillyrin as a potential antiosteoarthritic agent. This investigation employs a multifaceted approach. Initially, key action targets of phillyrin, along with its probable action pathways, were identified by molecular docking and network pharmacological techniques. These findings were subsequently confirmed through both in vivo and in vitro studies. Network pharmacological analysis revealed NFE2L2 (NRF2), NFKB1, TLR4, and SERPING1 as pivotal candidate targets for the treatment of osteoarthritis with phillyrin. Molecular docking revealed hydrogen bond interactions between phillyrin and Arg415, Arg483, Ser508, and Asn387 on the Nrf2 receptor, while electrostatic interactions occurred with residues Arg415 and Arg380. Experiments conducted in vitro indicated that phillyrin preconditioning hindered the IL-1β-induced expression of proinflammatory factors which included TNF-α, COX-2, IL-6, and iNOS. Furthermore, phillyrin counteracts the IL-1β-induced degradation of aggrecan and collagen II within the extracellular matrix (ECM). This protective action is caused by the inhibition of the NF-κB pathway by phillyrin. Additionally, the mitigation of chondrocyte aging by phillyrin was observed. Our investigation revealed that phillyrin mitigates inflammation and counteracts cartilage degeneration in osteoarthritis (OA) patients by suppressing inflammation in chondrocytes and impeding aging through suppression of the NF-κB pathway.

Osteoarthritis (OA), which is a major cause of serious arthralgia and disability among the elderly, has long plagued numerous populations. However, the specific molecular mechanisms involved in the etiology of OA are unclear. SIRT6 plays a critical function in the development of several inflammatory and aging-associated diseases. A study by D'Onofrio demonstrates that ergothioneine (EGT) is an effective activator of SIRT6. As revealed by previous reports, EGT exerts beneficial effects on the mouse body, including resistance to oxidation, tumor, and inflammation. Therefore, this work attempted to identify the inflammatory resistance of EGT and explore its effects on the incidence and development of OA. Mouse chondrocyte stimulation using varying levels of EGT and 10 ng/mL IL-1β. According to in vitro experiments, EGT significantly reduced the decomposition of collagen II and aggrecan in OA chondrocytes, as well as inhibited the overexpression of PGE2, NO, IL-6, TNF-α, iNOs, COX-2, MMP-13, and ADAMTS5. In the present work, EGT hindered the NF-κB activity by activating the SIRT6 pathway in OA chondrocytes, which in turn, significantly attenuated the inflammatory response resulting from IL to 1β. The inhibitory effect of EGT on the progression of OA was demonstrated by the mouse DMM model experiment. Thus, this study revealed that EGT was effective in anti-OA treatment.

Background: Perforator flap replantation is widely used to repair skin defects. However, ischaemia and ischaemia-reperfusion injury lead to flap necrosis, which limits the clinical application of this technique. Catalpol is the main active component of Rehmannia glutinosa. It is an iridoid glucoside compound with a variety of biological activities. We investigated whether Catalpol could promote perforator flap survival.Methods: Rats were randomly divided into control and Catalpol groups (n = 30 per group). On the 7th day after the operation, flap tissue was obtained to evaluate flap viability, flap perfusion, angiogenesis, apoptosis, oxidative stress and inflammation-related protein levels.Results: Unlike in the control group, Catalpol promoted the survival of the perforator flap, promoted angiogenesis, reduced apoptosis, alleviated oxidative stress, and depressed expressions of inflammatory proteins.Conclusions: Catalpol promotes the survival of perforator flaps by promoting angiogenesis, inhibiting apoptosis and oxidative stress, and dampening inflammation.

Cartilage endplate (CEP) degeneration has been considered as one of important factors related to intervertebral disc degeneration (IVDD). Previous researches have showed that Rac1 played a pivotal role in chondrocyte differentiation. However, the effect of Rac1 during the process of CEP degeneration remains unclear. Herein, we explored the effect of Rac1 on CEP degeneration and elucidated the underlying molecular mechanism. We found expression of Rac1-GTP increased in human-degenerated CEP tissue and IL-1β-stimulated rat endplate chondrocytes (EPCs). Our study revealed that Rac1 inhibitor NSC23766 treatment promoted the expression of collagen II, aggrecan and Sox-9, and decreased the expression of ADTAMTS5 and MMP13 in IL-1β-stimulated rat EPCs. Moreover, we also found that NSC23766 could suppress the activation of Wnt/β-catenin pathway, suggesting that the beneficial effects of Rac1 inhibition in EPCs are mediated through the Wnt/β-catenin signalling. Besides, puncture-induced rats models showed that NSC23766 played a protective role on CEP and disc degeneration. Collectively, these findings demonstrated that Rac1 inhibition delayed the EPCs degeneration and its potential mechanism may be associated with Wnt/β-catenin pathway regulation, which may help us better understand the association between Rac1 and CEP degeneration and provide a promising strategy for delaying the progression of IVDD.

Background The anatomical features of the thoracic nerve roots in connection with intervertebral discs may prevent surgery-related complications and improve patients' neurological functional status during thoracic spine surgery. There is limited literature evidence regarding this concept using cadavers. Purpose To elucidate the qualitative anatomical features of the thoracic nerve roots in connection with intervertebral discs. Material and Methods Fifteen formalin-preserved spine specimens were used in this study. Small pieces of stainless-steel wires were placed along the root sleeves from their points of origin, after exposing the dural sac and bilateral nerve roots. The standard anteroposterior and lateral radiographs were taken after the placement of the wires. Measurements were done on radiographs using the picture archiving communication system. Results Take-off angles of the nerve roots at the coronal plane gradually increased from the level of T2 (36.1 degrees +/- 2.72 degrees) to T9 (84.1 degrees +/- 1.84 degrees) and from T9, it decreased to T12 (46.3 degrees +/- 2.67 degrees). Similar variation tendency was discovered in take-off angles of the nerve roots at the sagittal plane. No consistent tendency was found both in the distance from the origin of the root sleeve to its superior and inferior vertebral endplate. Distance from the origin of the root sleeve to the posterior midline (DM) exponentially decreased from T1 (8.2 +/- 0.87 mm) to T4 (6.0 +/- 0.93 mm). It slowly increased from T5 (5.5 +/- 0.68 mm) to T12 (10.9 +/- 1.79 mm), with T5 having the smallest DM. Distance between the origins of neighboring nerve roots showed an obvious increase from the T1-T2 interval (23.1 +/- 2.22 mm) to T7-T8 interval (30.9 +/- 2.68 mm). However, it progressively decreased at the T10-T11 interval (26.0 +/- 2.40 mm). Conclusion The dimensions of the thoracic nerve roots vary greatly from T1 to T12 intervertebral discs. Sound knowledge of these anatomical features of the thoracic nerve is mandatory for the thoracic spine surgery, especially in the posterolateral approach and transforaminal endoscopic surgery.

Osteoarthritis (OA) is the most prevalent form of human arthritis which is characterized by the degradation of cartilage and inflammation. As a rare Sirt6 activator, cyanidin is the major component of anthocyanins commonly found in the Mediterranean diet, and increasing evidence has shown that cyanidin exhibits anti-inflammatory effects in a variety of diseases. However, the anti-inflammatory effects of cyanidin on OA have not been reported. In the present study, we identified that cyanidin treatment could strongly suppress the expression of NO, PGE2, TNF-α, IL-6, iNOs, COX-2, ADAMTS5 and MMP13, and reduce the degradation of aggrecan and collagen II in IL-1β-induced human OA chondrocytes, indicating the anti-inflammatory effect of cyanidin. Further investigation of the mechanism involved revealed that cyanidin could upregulate the Sirt6 level in a dose-dependent manner and Sirt6 silencing abolished the effect of cyanidin in IL-1β-stimulated human OA chondrocytes, indicating a stimulatory effect of cyanidin on Sirt6 activation. Meanwhile, we found that cyanidin could inhibit the NF-κB pathway in IL-1β-stimulated human OA chondrocytes and its effect may to some extent depend on Sirt6 activation, suggesting that cyanidin may exert a protective effect through regulating the Sirt6/NF-κB signaling axis. Moreover, the in vivo study also proved that cyanidin ameliorated the development of OA in surgical destabilization of the medial meniscus (DMM) mouse OA models. In conclusion, these results demonstrate that cyanidin may have therapeutic potential for the treatment of OA.

OBJECTIVE: The aim of the present study was to investigate the relationship between vacuum facet phenomena and lumbar instability in patients with degenerative spondylolisthesis (DS) in L4-L5. METHODS: Patients with L4-L5 DS who had both lumbosacral flexion-extension radiographs and computed tomography (CT) scans available for review from January 2016 to December 2017 were eligible for the present study. The dynamic motion index (DMI) of each patient was used to represent the percentage of slippage of L-L4 on the L5 vertebral disks on the flexion radiographs minus the percentage on the extension radiographs. The facet vacuum index refers to the average width of the facet vacuum on the left and right sides. RESULTS: A total of 67 patients with L4-L5 DS were included in the present study. Of the 67 patients, 35 had a vacuum facet phenomenon on their CTscan and 32 patients did not. The incidence of lumbar instability in the patients with a vacuum facet phenomenon was significantly greater than that in the patients without a vacuum facet phenomenon (P = 0.015). The mean DMI for the patients with a vacuum facet phenomenon was significantly greater than that for the patients without a vacuum facet phenomenon (P < 0.001). A positive linear correlation was found between the facet vacuum index and DMI for patients with a vacuum facet phenomenon (Pearson correlation coefficient, 0.597; P < 0.001). CONCLUSIONS: A linear correlation was found between the degree of segmental motion and the width of the vacuum facet phenomenon in patients with DS at L4-L5. Our study has shown that vacuum facet phenomena detected on the CT images of patients with DS are highly predictive of segmental instability.

Background: Cartilaginous endplate (CEP) degeneration is considered as one of the major causes of intervertebral disc degeneration (IVDD) which causes low back pain. Recent studies have proved that epigenetic alteration is involved in a variety of diseases. This work explored the role of histone methyltransferase enhancer of zeste homologue 2 (EZH2) in CEP degeneration, as well as its underlying epigenetic mechanisms, and confirmed the effect of EZH2 knockdown on delaying IVDD development. Methods: Western blotting, immunofluorescence staining, and ChIP assay were applied to demonstrate the molecular mechanism of EZH2 in CEP tissue. The therapeutic potential of EZH2 was investigated using puncture-induced rat models. Findings: The EZH2 expression was upregulated in human and rat CEP tissue. It was also found that the overexpression of EZH2 suppressed the expression of Collagen II, aggrecan and Sox-9, and promoted the expression of ADTAMTS5 and MMP13 in rat endplate chondrocytes (EPCs), which could be reversed by EZH2 silencing. The correlation between EZH2 and Sox-9 was further explored, while overexpression of Sox-9 could reverse the effect of EZH2 in rat EPCs. Moreover, inhibition of EZH2 upregulated the level of Sox-9 by demethylating H3K27me3 at Sox-9 promoter sites, revealing the regulatory mechanism of EZH2 on Sox-9. Meanwhile, puncture-induced rat models showed that EZH2 knockdown exerted a protective effect on CEP and disc degeneration. Interpretation: This study reveals that EZH2 inhibition is a promising strategy for mitigating the symptoms and progression of IVDD. (C) 2019 The Authors. Published by Elsevier B.V.

Objectives To evaluate hidden blood loss (HBL) and its possible risk factors among patients following expansive open-door laminoplasty (EOLP) for multilevel, cervical spondylotic myelopathy. Methods This was a retrospective analysis of data from patients over 18 years of age who underwent posterior cervical EOLP (from C3-C6) in our department from January 2017 to July 2018. HBL was calculated by deducting the observed perioperative blood loss from the calculated total blood loss (TBL) based on the fall in haematocrit level. Results 45 patients (35 men and 10 women) were identified. Mean ± SD HBL was 337.2 ± 187.8 ml, which was 46.8% of the total perioperative blood loss (705.2 ± 269.6 ml). Twenty-three patients developed postoperative anaemia. Posterior cervical soft tissue was positively correlated with both TBL and hidden blood loss (HBL) and hypertension was positively correlated with TBL. Conclusions HBL following cervical EOLP was significant and should be recognised as a detrimental factor to patient safety during the perioperative period, especially in patients with thick posterior cervical soft tissue.

ABSTRACT Purpose: To examine the hidden blood loss (HBL) in treatment of AO type A1-A3 thoracolumbar fractures with three different approaches and to explore the influential factors of HBL among patients after the surgery of internal fixation for thoracolumbar fractures. Methods: We retrospectively studied 85 patients in treatment of thoracolumbar fractures: 25 patients via percutaneous approach (Group A), 33 patients via paraspinal approach (Group B), and 27 patients via conventional open approach (Group C). The demographic information of the patients was collected. Each patient's preoperative and postoperative hematocrit were recorded and used for calculating the blood loss according to the Gross's formula. The difference of blood loss between the three groups was measured by ANOVA. And influential factors were further analyzed by multivariate linear regression analysis in each group. Results: The average HBL was 240.0 ± 65.1 mL in Group A, 313.7 ± 138.1 mL in Group B, and 382 ± 153.8 mL in Group C. There was statistical difference in the HBL between three groups (P = 0.000). However, multivariate linear regression analysis revealed that HBL of three approaches was not associated with age, gender, body mass index (BMI), percentage of height loss, percentage of height restoration, fracture type, or operation time. Conclusion: There was a substantial HBL in the treatment of thoracolumbar fractures, which was neglected by surgeons. Further investigation is necessary to study the risk factors for surgery on HBL in treatment of thoracolumbar fractures.

PURPOSE: This study examined the volume of hidden blood loss (HBL) and compared perioperative blood loss between minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) and open transforaminal lumbar interbody fusion (O-TLIF). METHODS: Forty-eight patients who were treated with MI-TLIF and 59 patients treated with O-TLIF were enrolled in this study. Patients' height, weight, and preoperative and postoperative hematocrit (Hct) were recorded and used to calculate total blood loss (TBL) according to the Gross formula. Each patient's HBL was calculated. The data were further analyzed by the Student t test and the chi(2) test. RESULTS: The visible blood loss (VBL) was 186 +/- 95 mL in the MI-TLIF; however, the HBL (423 +/- 233 mL; 66.5 +/- 16.1% of TBL) was twice the VBL. The VBL in the O-TLIF group was 471 +/- 147 mL, and the HBL was 271 +/- 223 mL (31.3 +/- 23.9% of TBL). Although TBL in MI-TLIF (602 +/- 251 mL) was less than in O-TLIF (742 +/- 275 mL), the HBL was significantly higher (P < 0.01). No difference in postoperative blood loss was observed between the 2 groups. Seven and 10 patients had preoperative anemia in the MI-TLIF group and the O-TLIF group, respectively, and 32 and 45 postoperatively. CONCLUSION: HBL is seriously underestimated and accounts for a large percentage of TBL in both MI-TLIF and O-TLIF. A correct understanding of HBL can ensure patient safety and improve postoperative rehabilitation.