Apigenin enhances viability of random skin flaps by activating autophagy.

Random skin flap is widely used in plastic surgery. However, flap necrosis caused by ischemia-reperfusion injury limits its clinical applications. Apigenin, a naturally occurring flavonoid mainly derived from plants, facilitates flap survival. In this study, we explored the effects of apigenin on flap survival and the underlying mechanisms. A total of 54 mice having a dorsal random flap model were randomly divided into control, apigenin, and apigenin +3-methyladenine groups. These groups were treated with dimethyl sulfoxide solution, apigenin, and apigenin +3-methyladenine, respectively. The animals were then euthanized to assess angiogenesis, apoptosis, oxidative stress, and autophagy levels through histological and protein analyses. Apigenin promotes survival of the skin flap area and reduces tissue edema. In addition, apigenin enhanced angiogenesis, attenuated apoptosis, alleviated oxidative stress, and activated autophagy. Interestingly, 3-methyladenine reversed the effects of apigenin on flap survival, angiogenesis, apoptosis, and oxidative stress through inhibition of autophagy. The findings of this study show that apigenin promotes angiogenesis, inhibits cell apoptosis, and lowers oxidative stress by mediating autophagy, thus the improving survival rate of random skin flaps.

Prevalence of the thoracic scoliosis in children and adolescents candidates for strabismus surgery: results from a 1935-patient cross-sectional study in China.

PURPOSE: No study so far has paid attention to strabismus-related spinal imbalance. This study aimed to determine the epidemiology of thoracic scoliosis in children and adolescents with strabismus and investigate the association of two diseases. METHODS AND DESIGN: A cross-sectional study. Study group consists of 1935 consecutive candidates for strabismus surgery (4-18 years); Control group consists of the age- and sex-matched patients with respiratory diseases. All subjects underwent a screening program based on chest plain radiographs using the Cobb method. Their demographic information, clinical variables and results of Cobb angle were recorded and analyzed. RESULTS: A significantly higher prevalence of thoracic scoliosis (289/1935, 14.94% versus 58/1935, 3.00%) was found in study group compared with control group. Among strabismic patients, the coronal thoracic scoliosis curve mainly distributed in right and in main thoracic (198/289) and in the curves 10°-19° (224/289); Age range 7-9 years (103/1935), female (179/1935) and concomitant exotropia patients (159/851) were more likely to have thoracic scoliosis. According to the logistic regression, thoracic scoliosis had no significant association with age, BMI, duration of illness and onset age (p > 0.05). However, gender, BCVA, type of strabismus and degree of strabismus showed a significant relationship with the prevalence of thoracic scoliosis (p < 0.05). CONCLUSIONS: With a pooled prevalence of 14.94%, strabismus patients showed a great higher risk of developing thoracic scoliosis. Screening for scoliosis in strabismus patients can be helpful to discover a high prevalence of potential coronal scoliosis. More attention should be paid to ophthalmological problems in patients with scoliosis. These slides can be retrieved under Electronic Supplementary Material.

Assessment of Neck Imbalance in Adolescent Idiopathic Scoliosis Patients: A Cross-Section Study Based on Body Image of 115 Patients with Main or Double Thoracic Curve.

OBJECTIVE: Neck imbalance negatively affects body aesthetics of adolescent idiopathic scoliosis (AIS) patients. The evaluation of neck imbalance is currently limited to radiographic parameters, but lacks visual indicators. Therefore, the purpose of this study was to establish indexes of neck imbalance based on body image and to investigate whether these indexes can truly reflect neck imbalance in AIS patients. METHODS: We performed a cross-sectional study at a single institution between June 2017 and September 2020 and there were 115 subjects involved in this research. All patients were diagnosed with adolescent idiopathic scoliosis, Lenke type I/II. Radiographic parameters measured included cervical axis tilt (CAT), T1 tilt, first rib angle (FRA), clavicle angle (CA), radiographic shoulder height (RSH), proximal thoracic curve (PTC), apical vertebra translation of proximal thoracic (AVT of PT), main thoracic curve (MTC), apical vertebra translation of main thoracic (AVT of MT) and coronal balance (CB/C7PL-CSVL). Neck imbalance indexes were obtained and measured following a standardized manner. Intra-class correlation coefficient (ICC) analysis was performed for neck imbalance indexes to determine their intra-observer and inter-observer reliability, and correlation tests were performed for neck imbalance indexes with the radiographic parameters mentioned above. RESULTS: Strong intraobserver and interobserver reliability were observed in neck imbalance index (NII) 1 (0.91 and 0.88), neck imbalance index 2 (0.85 and 0.81) and NII 3 (0.82 and 0.80), P < 0.05. Significant correlation was found in cervical axis tilt (R = 0.81 for NII 1, R = 0.77 for NII 2 and R = 0.78 for NII 3), T1 tilt (R = 0.43 for NII 1, R = 0.52 for NII 2 and R = 0.48 for NII 3), first rib angle (R = 0.41 for NII 1, R = 0.48 for NII 2 and R = 0.43 for NII 3), proximal thoracic curve (R = 0.36 for NII 2) and apical vertebra translation of proximal thoracic (R = -0.37 for NII 2 and R = -0.35 for NII 3) with neck imbalance indexes. Neck imbalance index 1 showed the highest correlation with cervical axis tilt (R = 0.81, P < 0.01). CONCLUSIONS: Neck imbalance indexes established in our study were in good correlation with cervical axis tilt (CAT), At the meantime, they showed significant correlations with T1 tilt and first rib angle (FRA). Our study provides a practical method for measurement of neck imbalance regarding realistic perspective and makes up for the lack of photographic indexes about neck imbalance.

18ß-Glycyrrhetinic acid inhibits IL-1ß-induced inflammatory response in mouse chondrocytes and prevents osteoarthritic progression by activating Nrf2.

Osteoarthritis (OA) is presently the most prevalent form of chronic degenerative joint disease, which is characterized by erosion of articular cartilage, subchondral bone sclerosis and synovitis. Accumulating evidence has revealed that 18ß-glycyrrhetinic acid (18ß-GA), a major bioactive component derived from Glycyrrhiza glabra, exerts anti-inflammatory effects on several diseases. However, the anti-inflammatory effects of 18ß-GA on OA remain undetermined. The present study aimed to investigate the anti-inflammatory effects of 18ß-GA on chondrocytes and the therapeutic effects on destabilization of the medial meniscus destabilization (DMM) mouse models of OA. For the in vivo study, we randomly divided the mice into three groups: vehicle control (n = 15), sham (n = 15) and 18ß-GA (n = 15) groups, and treated them with similar doses (50 mg kg-1 day-1) of 18ß-GA or saline. Cartilage tissues were harvested from the mice for histological analyses eight weeks after operation. For the in vitro studies, mouse chondrocytes were administered with 10 ng mL-1 interleukin-1ß (IL-1ß) after being treated with 18ß-GA at various concentrations. In vitro assays revealed that treatment with 18ß-GA considerably suppressed the expression of pro-inflammatory mediators and cytokines, including prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), nitric oxide (NO), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and interleukin-6 (IL-6), which were induced by IL-1ß. Furthermore, 18ß-GA decreased the expression of matrix-degrading proteases, including matrix metalloproteinase 13 (MMP13) and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), in a concentration-dependent manner, which mediated extracellular matrix (ECM) degradation. 18ß-GA reversed aggrecan and type II collagen degradation. Furthermore, we observed that 18ß-GA significantly suppressed IL-1ß-induced nuclear factor kappa B (NF-κB) activation by activating the nuclear factor erythroid-derived 2-like 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway in vitro and in vivo. Experiments demonstrated that 18ß-GA might alleviate the progression of OA in the DMM mouse model in vivo. The findings demonstrate that 18ß-GA reduces inflammation induced by IL-1ß in chondrocytes. Therefore, 18ß-GA could be a potential therapeutic agent for OA.

No evidence of a correlation between lumbar spinal subtypes and intervertebral disc degeneration among asymptomatic middle-aged and aged patients.

The aim of the present study was to identify whether lumbar spinal subtypes (LSS) were associated with lumbar disc degeneration (LDD) among asymptomatic middle-aged and aged subjects. A cohort of 158 asymptomatic Chinese adults aged >40 years was recruited and 97 volunteers that met the inclusion criteria with complete information available were selected for inclusion. According to spinal morphology, volunteers were divided into four subtypes based on the classification of Roussouly. After baseline information was collected and spinopelvic parameters were measured, the data were compared among the four groups. According to the Pfirrmann classification, the degree of LDD was evaluated at each level on the MRI. For grades I-V, LDD at each level was effectively compared. Each of the four LSS from I to IV according to Roussouly classification from types I to IV were comprised of 25 (25.8%), 19 (19.6%), 38 (39.2%) and 15 (15.5%) of volunteers, respectively. Lumbar lordosis, sacral slope and pelvic incidence were significantly different among the four sub-types (P<0.001 for each), but no difference in pelvic tilt was observed (P=0.21). From types I to IV LSS, the proportion of disc degeneration was found to be 44, 52, 50 and 48%, respectively, which exhibited no statistically significant difference among LSS. No correlation between LSS and intervertebral disc degeneration was obtained among the asymptomatic middle-aged and aged subjects. The present study provides a reference for spinal surgery and indicated that additional risk factors should be assessed in the asymptomatic population of this age group, particularly in terms of differentially expressed genes.

Stachydrine ameliorates the progression of intervertebral disc degeneration via the PI3K/Akt/NF-κB signaling pathway: in vitro and in vivo studies.

Intervertebral disc degeneration (IDD) has been reported to be a major cause of low back pain. Stachydrine (STA) is present in the fruit juice of the Citrus genus and Leonurus heterophyllus, in non-negligible concentrations. In our study, we examined the protective effects of STA against IDD development as well as its underlying mechanism of action using both in vitro and in vivo experiments. STA exerted protective effects on the anabolism and catabolism of the extracellular matrix (ECM) in IL-1ß-treated NPCs and inhibited the expression of pro-inflammatory factors in vitro. Mechanistically, STA suppressed the IL-1ß-induced activation of PI3K/Akt/NF-κB signalling pathway cascades. Moreover, it was also demonstrated in molecular docking studies that STA has strong binding abilities to PI3K. Furthermore, STA ameliorated the progression of the IDD process in vivo in the puncture-induced rat model. In summary, our findings demonstrated that STA ameliorates the progression of IDD via the PI3K/Akt/NF-κB signalling pathway, which makes STA a promising therapeutic agent for the treatment of IDD.