"Adjacent Bed Effect" of Total Knee Arthroplasty Patients During the Perioperative Period.

BACKGROUND: Knee osteoarthropathy is one of the most common degenerative joint diseases in the elderly, total knee arthroplasty (TKA) is the most commonly used treatment for end-stage knee osteoarthropathy. Negative emotions such as anxiety have been extensively documented in knee osteoarthropathy patients. AIM: This study aimed to investigate the Emotional Contagion during hospitalization in patients undergoing TKA. METHODS: Eligible subjects were divided into three case groups according to their anxiety states and bed arrangement. All subjects underwent a unilateral, cemented TKA under general anesthesia. Post-operative recovery outcomes including pain, pain behavior and physical function were recorded pre-operation, 1-day, 1 week, 2-weeks, 1-month and 3-months post-operation. RESULTS: A total of 38 subjects were included in the final analysis. Subjects with anxiety had higher Visual Analogue Scale pain scores, PROMIS-Pain Behavior scores than subjects without anxiety in the Contagion Group preoperation (p ≤ .05). Non-anxiety subjects hospitalized in beds physically adjacent to anxiety subjects experienced more severe pain and poorer function (p ≤ .05). After discharge, all clinical outcomes gradually became lower than anxiety subjects in the Contagion Group, reaching levels similar to non-anxiety subjects in the No Contagion Group within 1 month (p>.05). CONCLUSIONS: This study showed that patients with anxiety may have an "Adjacent Bed Effect" on patients with TKA in the adjacent bed, which may be associated with poorer postoperative recovery, including pain and physical function. We speculate this phenomenon can be effectively avoided by the nursing team through accurately assessing psychological status and reasonable bed arrangements in the inpatient assessment phase.

Electrophoretic deposition of Ru(bpy)32+ in vertically-ordered silica nanochannels: A solid-state electrochemiluminescence sensor for prolidase assay.

Prolidase (PLD) plays a crucial role as a dipeptidase in various physiological processes, specifically involved in the cleavage of proline-containing dipeptides for efficient recycling of proline. The accurate determination of PLD activity holds significant importance in clinical diagnosis. Herein, a solid-state electrochemiluminescence (ECL) biosensor was developed to address the urgent need for PLD assay. The Ru(bpy)32+ was electrophoretically deposited within the nanochannels of vertically-ordered mesoporous silica film (VMSF) on indium tin oxide (ITO) electrodes. The Ru(bpy)32+-deposited VMSF/ITO (Ru-VMSF/ITO) exhibited a remarkable ECL response towards proline, attributed to the enhanced concentration of the reactants and improved electron transfer resulting from the nanoconfinement effect. As PLD specifically enzymolyzed the Gly-Pro dipeptide to release proline, a proline-mediated biosensor was developed for PLD assay. Increased PLD activity led to enhanced release of proline into the porous solid-state ECL sensors, resulting in a more robust ECL signal. There was a linear relationship between ΔECL intensity and logarithmic concentration of PLD in the range of 10-10000 U/L, with a detection limit of 1.98 U/L. Practical tests demonstrated the reliability and convenience of the proposed bioassay, making it suitable for widespread application in PLD assays.

[Application of femoral I.D.E.A.L localization in anterior cruciate ligament reconstruction with single bundle anterior cruciate ligament].

OBJECTIVE: To evaluate the effect of femoral I.D.E.A.L localization in single bundle anterior cruciate ligament reconstruction (ACLR). METHODS: From January 2019 to October 2022, 122 patients with anterior cruciate ligament injury were treated with ACLR, including 83 males and 39 females. The age ranged from 23 to 43 years old, with an average of (32.19 ±8.55) years old. The course of disease ranged from 1 week to 6 months. According to the different surgical schemes, the patients were divided into two groups, namely the traditional group, which adopted the over-the-top femoral lateral positioning scheme, including 64 patients. The I.D.E.A.L group adopted the I.D.E.A.L femoral lateral positioning scheme, including 58 patients. The patient has pain and dysfunction of knee joint before operation. MRI of knee joint indicates anterior cruciate ligament injury. The visual analogue scale(VAS), International Knee Documentation Committee(IKDC) scoring system and Lysholm scoring system were used to evaluate the knee joint function of the patient. KT-2000 was used to detect the recovery of knee joint after operation and to count the postoperative complications. RESULTS: The wounds healed well after operation. One hundred and twenty-tow patients were followed up for 15 to 46 months, with an average of (25.45±9.22) months. The knee joint stability of patients after operation was significantly increased. The VAS at 1 day and 1 week after operation of patients in the I.D.E.A.L group was significantly lower than that in the traditional group(P<0.05). The IKDC score and Lysholm score of patients in the I.D.E.A.L group were significantly higher than those in the traditional group(P<0.05). In the traditional group, there were 6 cases of short-term (<1 month) complications and 19 cases of long-term (≥1 month)complicatios. In the I.D.E.A.L group, there were 3 cases of short-term complications and 7cases of long-term complications(P<0.05). CONCLUSION: The single bundle anterior cruciate ligament reconstruction and femoral I.D.E.A.L positioning can achieve better early postoperative effect and reduce early postoperative pain.

Influence of Nano-SiO2 Content on Cement Paste and the Interfacial Transition Zone.

Nano-SiO2 (NS) is widely used in cement-based materials due to its excellent physical properties. To study the influence of NS content on a cement paste and the interfacial transition zone (ITZ), cement paste samples containing nano content ranging from 0 to 2% (by weight of cement) were prepared, and digital image correlation (DIC) technology was applied to test the mechanical properties. Finally, the optimal NS content was obtained with statistical analysis. The mini-slump cone test showed that, with the help of superplasticizer and ultrasonic treatment, the flowability decreased continuously, as the NS content increased. The DIC experimental results showed that NS could effectively improve the mechanical properties of the cement paste and the ITZ. Specifically, at the content level of 1%, the elastic modulus of cement paste and ITZ was 20.95 GPa and 3.20 GPa, respectively. When compared to that without nanomaterials, the increased amplitude was 73.50% and 90.50%, respectively. However, with the further increase in NS content, the mechanical properties decreased, which was mainly caused by the agglomeration of nanomaterials. Additionally, the NS content did not exhibit a significant effect on the thickness of the ITZ, and its value was maintained at 76.91-91.38 µm. SEM confirmed that NS would enhance the microstructure of both cement paste and ITZ.

Combined healthy lifestyle in early pregnancy and risk of gestational diabetes mellitus: A prospective cohort study.

OBJECTIVE: To examine the association of a combined healthy lifestyle in early pregnancy with gestational diabetes mellitus (GDM) risk. DESIGN, SETTING AND POPULATION: A Chinese prospective cohort study with 6980 pregnant women. METHODS: Individual modifiable lifestyle factors were assessed in early pregnancy and a combined lifestyle score was derived from the sum of the lifestyle factors, with a higher score indicating a healthier lifestyle. The association of a combined healthy lifestyle with GDM risk was examined. MAIN OUTCOME MEASURES: Gestational diabetes mellitus was diagnosed in middle pregnancy according to the International Association of Diabetes and Pregnancy Study Group criteria or diagnoses in medical records. RESULTS: Overall, 501 (7.2%) pregnant women were diagnosed with GDM. Being physically active (total energy expenditure in upper three quintiles, i.e. ≥100.1 metabolic equivalent of task [MET]-hours/week; odds ratio [OR] 0.76, 95% confidence interval [CI] 0.63-0.92), healthy diet (total intake of vegetables and fruits ≥5 times/day; OR 0.74, 95% CI 0.59-0.94), sufficient sleep (night-time sleep duration ≥7 hours/night; OR 0.66, 95% CI 0.48-0.90) and healthy weight (early-pregnancy BMI <24.0 kg/m2 ; OR 0.57, 95% CI 0.46-0.71) were associated with lower GDM risk. The GDM risk decreased linearly across the combined lifestyle score (Ptrend <0.001): women with 2, 3 and 4 lifestyle factors compared with those with 0-1 factor had 38% (OR 0.62, 95% CI 0.46-0.84), 57% (OR 0.43, 95% CI 0.31-0.58) and 66% (OR 0.34, 95% CI 0.22-0.52) lower risks of GDM, respectively. CONCLUSION: A healthy lifestyle in early pregnancy was associated with a substantially lower GDM risk.

Transcriptome-Based Construction of the Gibberellin Metabolism and Signaling Pathways in Eucalyptus grandis × E. urophylla, and Functional Characterization of GA20ox and GA2ox in Regulating Plant Development and Abiotic Stress Adaptations.

Gibberellins (GAs) are the key regulators controlling plant growth, wood production and the stress responses in perennial woody plants. The role of GA in regulating the above-mentioned processes in Eucalyptus remain largely unclear. There is still a lack of systematic identification and functional characterization of GA-related genes in Eucalyptus. In this study, a total of 59,948 expressed genes were identified from the major vegetative tissues of the E. grandis × E. urophylla using transcriptome sequencing. Then, the key gene families in each step of GA biosynthesis, degradation and signaling were investigated and compared with those of Arabidopsis, rice, and Populus. The expression profile generated using Real-time quantitative PCR showed that most of these genes exhibited diverse expression patterns in different vegetative organs and in response to abiotic stresses. Furthermore, we selectively overexpressed EguGA20ox1, EguGA20ox2 and EguGA2ox1 in both Arabidopsis and Eucalyptus via Agrobacterium tumefaciens or A. rhizogenes-mediated transformation. Though both Arabidopsis EguGA20ox1- and EguGA20ox2-overexpressing (OE) lines exhibited better vegetative growth performance, they were more sensitive to abiotic stress, unlike EguGA2ox1-OE plants, which exhibited enhanced stress resistance. Moreover, overexpression of EguGA20ox in Eucalyptus roots caused significantly accelerated hairy root initiation and elongation and improved root xylem differentiation. Our study provided a comprehensive and systematic study of the genes of the GA metabolism and signaling and identified the role of GA20ox and GA2ox in regulating plant growth, stress tolerance, and xylem development in Eucalyptus; this could benefit molecular breeding for obtaining high-yield and stress-resistant Eucalyptus cultivars.

Long-term glycemic variability and risk of adverse health outcomes in patients with diabetes: A systematic review and meta-analysis of cohort studies.

AIMS: To quantify associations of different metrics of long-term glycemic variability (GV) with multiple adverse diabetes-related outcomes. METHODS: We searched PubMed and Embase from database inception to 23 August 2021. GV was based on measurements of HbA1c or fasting plasma glucose (FPG) and calculated by standard deviation (SD), coefficient of variance (CV) or other metrics. Outcomes included mortality, cardiovascular disease (CVD), renal disease, peripheral neuropathy, retinopathy, dementia and cancer. Random-effects meta-analyses were adopted to pool the relative risks (RRs). RESULTS: Seventy-five articles with 2,051,701 participants were included. When comparing top with bottom quartiles, HbA1c variabilities were associated with all-cause mortality (RRCV = 1.63, 95 % CI 1.37-1.92; RRSD = 1.87, 1.55-2.26), CVD (RRCV = 1.38, 1.07-1.78; RRSD = 1.34, 1.12-1.59), renal disease (RRCV = 1.43, 1.18-1.74; RRSD = 1.44, 1.24-1.67), and peripheral neuropathy (RRCV = 1.84, 1.40-2.43; RRSD = 1.98, 1.51-2.61), but not retinopathy. FPG variabilities were associated with all-cause mortality (RRCV = 1.59, 1.43-1.78; RRSD = 1.67, 1.26-2.20), renal disease (RRCV = 1.77, 1.32-2.38), and retinopathy (RRCV = 1.92, 1.10-3.35), but not CVD and peripheral neuropathy. Associations of GV with Alzheimer's disease (RRHbA1c-CV = 1.38, 1.13-1.70; RRFPG-CV = 1.32, 1.07-1.63) and cancer (RRHbA1c-SD = 2.19, 1.52-3.17; RRFPG-CV = 3.64, 2.21-5.98) were each found significant in one study. CONCLUSIONS: Long-term GV was associated with multiple adverse diabetes-related outcomes, while the strength of associations varied. The findings support the use of long-term GV for diabetes management in clinical practice.

First Report of Powdery Mildew in Eucalyptus Caused by Erysiphe neolycopersici in China.

Eucalyptus is one of the most fast-growing and widely planted hardwood trees in the tropical and subtropical regions (Grattapaglia and Kirst, 2008). In December 2021, powdery mildew diseases were observed on the Eucalyptus urophylla, E. urophylla × E. grandis, E. grandis × E. urophylla, and E. grandis trees growing in the Eucalyptus garden of the Guangxi University campus in Nanning (108°22'E, 22°48'N) of Guangxi Zhuang Autonomous Region, where is the main plantation area for Eucalyptus. The spread of this disease would bring potential challenges on the Eucalyptus plantation management in this region of China. The early symptoms of this disease in Eucalyptus were that the irregular white spots with surface-attached powder was observed on the leaves. At the late stages, this symptom was diffused to the whole leaves and even petioles and stems. It would finally cause significant defoliation, but barely lead to plant death in Eucalyptus. Microscopic observation showed that the mycelium was straight or flexuous, hyaline, thin-walled, septate, branched, and 3-7 µm wide (n = 50; average 4.86 µm). The appressorium was lobed and attached to one end of the mycelium alone, or paired attached to both ends of the mycelium. The conidiophore was straight or flexuous, unbranched, 54-100 × 6-10 µm (n = 40; average 75.47 µm × 8.22 µm). One to 3 conidium were connate on the conidiophores. Foot-cells were straight or flexuous at base, 5-8 µm wide (n = 40; average 6.53 µm). The conidium were ellipsoid or oval, and the size was 38-56 × 12-21 µm (n = 70; average 44.92 µm × 15.69 µm). The lobed or rod-shaped bud tube was produced at the conidium. According to the morphology, the fungus was identified as Erysiphe neolycopersici (Hsiao, et al. 2022). For the molecular characterization of the isolate, the sequences of the internal transcribed spacer (ITS), the 18S and 28S large subunit ribosomal DNA (SSU and LSU) (Scholin et al. 1994 , White et al. 1990), were sequenced and deposited in GenBank (OM422667, OM424285 and ON514159). The phylogenetic analysis showed that the ITS sequence showed 100% identity with sequences of E. neolycopersici (MW082786, MT370492, and JQ972700). The 28S rDNA sequence had the highest identity (99.69%) with that of E. neolycopersici (LC371327, LC371320, and OM368490). The SSU sequence had the highest identity (99.72%) with that of E. neolycopersici (LC516961). The pathogenicity test of the fungus was repeated thrice following the Koch's postulates. The diseased leaves were gently rubbed against 3 to 4 healthy mature leaves of more than five E. grandis seedlings (two-month-old). The inoculated and control plants were then cultured in the greenhouse (25 ℃, 16-h light/8-h dark and 70% humidity). Similar disease symptoms were observed on the inoculated leaves, but not on the control leaves seven days after inoculation. The isolates from three independent experiments were morphologically and genetically identical with the original isolate. As far as we know, this study is the first report of powdery mildew disease in Eucalyptus caused by E. neolycopersici in China.

The Effect of Medial Branch Block on Postoperative Residual Pain Relieve After Percutaneous Kyphoplasty: A Randomized Controlled Trial With 12-Month Follow-up.

BACKGROUND: Percutaneous kyphoplasty (PKP) is a minimally invasive technique, and effective treatment, for an osteoporotic vertebral compression fracture (OVCF). Residual back pain is the most common complication of PKP. Medial branch block (MBB) is a treatment option for painful OVCF, it can break the vicious cycle to release short- or long-term pain. OBJECTIVES: We aimed to determine the effects of MBB on postoperative residual back pain in OVCF patients after PKP surgery. STUDY DESIGN: A randomized, controlled, single-center trial. SETTING: Medical university center and local hospitals. METHODS: A total of 198 patients were recruited and randomly assigned to either the MBB or Non-MBB group. In the MBB group, patients received MBB during PKP surgery, the injection contained a mixture of lidocaine and budesonide. The Non-MBB group was injected with normal saline in the target nerve area during PKP surgery. The primary outcome was back pain assessed by the Visual Analog Scale (VAS), and residual back pain was defined as a VAS score greater than or equal to 4. The secondary outcomes included physical function assessed by Patient-Reported Outcome Measurement Information System Physical Function (PROMIS PF) and satisfaction with surgery was assessed using the S6 satisfaction scale. All parameters were measured at baseline, 1 day, 1 week, 1 month, 3, 6, and 12 months after the intervention. RESULTS: A total of 179 patients, including 91 patients in the MBB group and 88 patients in the Non-MBB group, were included for a comprehensive assessment. The VAS score in the MBB group was significantly lower than in the Non-MBB group within a one-month follow-up. PROMIS PF score in the MBB group was significantly higher than in the Non-MBB group within a one-month follow-up. The incidence of residual back pain in the MBB group was lower than the Non-MBB group within a one-month follow-up. The MBB group had a significantly higher satisfaction rate compared with the Non-MBB group at final follow-up. LIMITATIONS: Firstly, patients are from a single institution and the sample size is small. Secondly, some of the potential factors which may lead to back pain, such as infection, new symptomatic compression fracture, and serious cement leakage, did not occur. Thirdly, the conservative treatment group is not included. Finally, we were unable to determine individual differences in pain tolerance. CONCLUSIONS: MBB can effectively relieve back pain and reduce the incidence of residual back pain in OVCF patients after PKP surgery. Besides, it can also significantly improve postoperative physical function and patients' satisfaction with treatment.

An assessment of morphological and pathological changes in paravertebral muscle degeneration using imaging and histological analysis: a cross-sectional study.

BACKGROUND: The high signal of paravertebral muscle (PVM) on T2-weighted image (T2WI) is usually considered to be fatty degeneration. However, it is difficult to distinguish inflammatory edema from fatty degeneration on T2WI. The purpose of this study was to identify different types of PVM high signal in patients with low back pain (LBP) through magnetic resonance imaging (MRI) and histology. METHODS: Seventy patients with LBP underwent MRI. The signal change of multifidus both on T2WI and fat suppression image (FSI) was quantified by Image J. Furthermore, 25 of the 70 patients underwent surgery for degenerative lumbar disease and their multifidus were obtained during the operation. Histological analysis of the samples was performed by HE staining. RESULT: Three types of PVM signal changes were identified from the MRI. Type 1 (n = 36) indicated fatty degeneration characterized by a high signal on T2WI and low signal on FSI. High signal on both T2WI and FSI, signifying type 2 meant inflammatory edema (n = 9). Type 3 (n = 25) showed high signal on T2WI and partial signal suppression on FSI, which meant a combination of fatty degeneration and inflammatory edema. Histological results were consistent with MRI. Among the 25 patients who underwent surgery, type 1 (n = 14) showed adipocytes infiltration, type 2 (n = 3) showed inflammatory cells infiltration and type 3 (n = 8) showed adipocytes and inflammatory cells infiltration. CONCLUSION: From our results, there are three types of pathological changes in patients with PVM degeneration, which may help to decide on targeted treatments for LBP.

BdFAR4, a root-specific fatty acyl-coenzyme A reductase, is involved in fatty alcohol synthesis of root suberin polyester in Brachypodium distachyon.

Suberin is a complex hydrophobic polymer of aliphatic and phenolic compounds which controls the movement of gases, water, and solutes and protects plants from environmental stresses and pathogenic infection. The synthesis and regulatory pathways of suberin remain unknown in Brachypodium distachyon. Here we describe the identification of a B. distachyon gene, BdFAR4, encoding a fatty acyl-coenzyme A reductase (FAR) by a reverse genetic approach, and investigate the molecular relevance of BdFAR4 in the root suberin synthesis of B. distachyon. BdFAR4 is specifically expressed throughout root development. Heterologous expression of BdFAR4 in yeast (Saccharomyces cerevisiae) afforded the production of C20:0 and C22:0 fatty alcohols. The loss-of-function knockout of BdFAR4 by CRISPR/Cas9-mediated gene editing significantly reduced the content of C20:0 and C22:0 fatty alcohols associated with root suberin. In contrast, overexpression of BdFAR4 in B. distachyon and tomato (Solanum lycopersicum) resulted in the accumulation of root suberin-associated C20:0 and C22:0 fatty alcohols, suggesting that BdFAR4 preferentially accepts C20:0 and C22:0 fatty acyl-CoAs as substrates. The BdFAR4 protein was localized to the endoplasmic reticulum in Arabidopsis thaliana protoplasts and Nicotiana benthamiana leaf epidermal cells. BdFAR4 transcript levels can be increased by abiotic stresses and abscisic acid treatment. Furthermore, yeast one-hybrid, dual-luciferase activity, and electrophoretic mobility shift assays indicated that the R2R3-MYB transcription factor BdMYB41 directly binds to the promoter of BdFAR4. Taken together, these results imply that BdFAR4 is essential for the production of root suberin-associated fatty alcohols, especially under stress conditions, and that its activity is transcriptionally regulated by the BdMYB41 transcription factor.

Maltol inhibits the progression of osteoarthritis via the nuclear factor-erythroid 2-related factor-2/heme oxygenase-1 signal pathway in vitro and in vivo.

Osteoarthritis (OA) is a common degenerative joint disease characterized by articular cartilage degeneration and inflammation. Currently, there is hardly any effective treatment for OA due to its complicated pathology and the severe side effects of the treatment drugs used. It has been reported that maltol, a Maillard reaction product derived from ginseng, inhibits inflammation and oxidative stress in several animal models. However, the potential anti-inflammatory effects of maltol in OA treatment are unknown. This study aimed to evaluate the anti-inflammatory effects of maltol on interleukin (IL)-1ß-induced mouse chondrocytes and protective effects of maltol on these chondrocytes in medial meniscus destabilization (DMM) OA mouse models. Mice, randomly divided into maltol (n = 15), vehicle (n = 15) and control (n = 15) groups were treated with the same dose of maltol or saline, respectively. The cartilage tissues were extracted for histological analysis 8 weeks postoperative. For the in vitro studies, chondrocytes were treated with 10 ng mL-1 IL-1ß combined with maltol at different concentrations. In vitro assays showed that the maltol pre-treatment significantly inhibited the expressions of multiple inflammatory factors induced by IL-1ß, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α). In addition, maltol alleviated the degradation of the extracellular matrix (ECM) by inhibiting the expressions of matrix metalloproteinase-13 (MMP13) and thrombospondin motif 5 (ADAMTS5), as well as reversing the degradation of aggrecan and collagen II. Moreover, maltol suppressed nuclear factor kappa B (NF-κB) signaling by activating the nuclear factor-erythroid 2-related factor-2 (Nrf2) in in vitro and in vivo studies. These findings indicate that maltol reduces the inflammation induced by IL-1ß in chondrocytes. Therefore, the results of this study indicated that maltol may be a potential drug for the effective treatment of OA.

Assessment of the cross-sectional areas of the psoas major in patients with adolescent idiopathic scoliosis before skeletal maturity.

BACKGROUND: The psoas major (PM) can support the lumbar spine and plays an important role in lumbar movement and maintaining lumbar curvature. PURPOSE: To analyze morphological changes of PM and its relation with the severity of adolescent idiopathic scoliosis (AIS). MATERIAL AND METHODS: The study was conducted on patients with AIS (age range = 10-18 years) with primary lumbar scoliosis. The cross-sectional area (CSA) of the PM at the L1-L5 levels were measured. The CSA of the PM in patients with AIS was compared with the average CSA of the PM in age-matched controls. The difference in PM at the apical vertebrae level was compared with the Cobb angle to determine the association between PM imbalance and severity of scoliosis. RESULTS: The CSA of the PM was larger on the concave side than the convex side at the apical vertebrae level and other lumber levels. Patients with a larger Cobb angle had statistically higher PM imbalance at the apical vertebrae level. The CSA of the PM on both the concave and convex sides of patients with AIS were larger than the average CSA of controls aged 16-18 years; however, there was no significant difference between patients with AIS and controls aged 10-15 years. CONCLUSION: There is a significant PM imbalance in patients with AIS before skeletal maturity, and the imbalance is related to the severity of scoliosis. The morphology of PM changed with the progression of scoliosis.

Inhibition of Rac1 activity by NSC23766 prevents cartilage endplate degeneration via Wnt/ß-catenin pathway.

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-1ß-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-1ß-stimulated rat EPCs. Moreover, we also found that NSC23766 could suppress the activation of Wnt/ß-catenin pathway, suggesting that the beneficial effects of Rac1 inhibition in EPCs are mediated through the Wnt/ß-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/ß-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.

Glycyrrhizin inhibits osteoarthritis development through suppressing the PI3K/AKT/NF-κB signaling pathway in vivo and in vitro.

Osteoarthritis (OA) is a serious and frequently occurring disease in the elderly, characterized by cartilage degeneration and proliferation of bone structure. Glycyrrhizin, a compound extracted from licorice, has been reported to have various important biological activities, such as antioxidant properties and anti-inflammatory action. However, it has not been reported whether glycyrrhizin has a positive effect on OA development. Our study aimed to evaluate the effects of glycyrrhizin on human OA chondrocytes. In the present study, we discovered that glycyrrhizin remarkably suppressed the interleukin (IL)-1ß-induced level of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and the production of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOs), metalloproteinase3 (MMP3), metalloproteinase13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs5 (ADAMTS5). In addition, glycyrrhizin inverted the degradation of aggrecan and collagen II. Moreover, it significantly inhibited IL-1ß-stimulated PI3K/AKT phosphorylation and NF-κB mobilization in human OA chondrocytes. In vivo, glycyrrhizin treatment prevented the destruction of cartilage in mice OA models. In summary, all the results demonstrate that glycyrrhizin may be a potential therapeutic approach for OA.

The projection of the thoracic nerve roots and their connection with intervertebral discs: a cadaver and radiological study.

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°±2.72°) to T9 (84.1°±1.84°) and from T9, it decreased to T12 (46.3° ± 2.67°). 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.

Inhibition of EZH2 ameliorates cartilage endplate degeneration and attenuates the progression of intervertebral disc degeneration via demethylation of Sox-9.

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. FUNDING: This study was funded by the Natural Science Foundation of Zhejiang Province (Y16H060034). Authors declare that the funders had no involvement in the study design, data analysis and interpretation of the results.

Cyanidin ameliorates the progression of osteoarthritis via the Sirt6/NF-κB axis in vitro and in vivo.

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-1ß-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-1ß-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-1ß-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.