Beyond Growth Hormone: Association of Short Stature Types and Growth Hormones With Scoliosis.

STUDY DESIGN: Cross-sectional and retrospective cohort study. OBJECTIVE: We investigated the effect of 3 types of short stature [partial growth hormone deficiency (GHD), GHD, and idiopathic short stature (ISS)] and recombinant human growth hormone (rhGH) therapy on scoliosis. SUMMARY OF BACKGROUND DATA: In short stature, rhGH is widely used and the concentration of growth hormone varies among types. The epidemiologic characteristics of scoliosis and the role of rhGH in scoliosis remain unclear. PATIENTS AND METHODS: A cross-sectional study was conducted among 3896 patients with short stature (partial GHD, GHD, and ISS), and a 1:1 age and sex-matched control group with preexisting whole-spine radiographs. The cohort study included 2605 subjects who underwent radiography more than twice to assess scoliosis development, progression, and the need for bracing and surgery. Adjusted logistic regression was used to assess differences in the prevalence of scoliosis among patients with partial GHD, GHD, ISS, and controls. The Kaplan-Meier method was used to analyze the time course of scoliosis development and progression. Cox regression was applied to assess the independent factors related to scoliosis development and progression. Mendelian randomization analyses were also performed. RESULTS: Compared with controls, patients with short stature had a higher incidence of scoliosis (34.47% in partial GHD, 31.85% in GHD, 32.94% in ISS vs . 8.83% in control, P < 0.001), a higher risk of scoliosis development [hazard ratio (HR) = 1.964 in partial GHD, P < 0.001; HR = 1.881 in GHD, P = 0.001; HR = 1.706 in ISS, P = 0.001), but not a higher risk of progression, brace, or surgery. Among the 3 types of short stature, there were no differences in the incidence, development, and progression of scoliosis or the need for bracing or surgery. RhGH treatment increased the risk of scoliosis development in each short-stature group (HR = 2.673 in partial GHD, P < 0.001; HR = 1.924 in GHD, P = 0.049; HR = 1.564 in ISS, P = 0.004). Vitamin D supplementation was protective against scoliosis development (HR = 0.456 in partial GHD, P = 0.003; HR = 0.42 in GHD, P = 0.013; HR = 0.838 in ISS, P = 0.257). CONCLUSIONS: More attention should be paid to the spinal curve in patients with partial GHD, GHD, or ISS. For short stature treated with rhGH, the risk of scoliosis development was increased. Vitamin D supplementation may be beneficial for prevention. LEVEL OF EVIDENCE: Level III.

Snacking behaviour and nutrients intake among 11-16 years-old students from two different boarding system schools.

This study's main objective was to investigate the difference between snacking behaviors and dietary nutrient intake in boarding system students. A cross-sectional study was conducted at Beijing's closed and semi closed boarding management school. The snack consumption questionnaire collected snack consumption behaviors; three-day recall periods for food consumption data were collected through the canteen weighing method and 24-h dietary recall of students' intakes. For closed and semi closed boarding management schools, the percentage of never having snacking behaviors was 12.95% and 2.69% on weekdays and 2.16% and 4.19% on weekends. A higher proportion of respondents chose unhealthy snacks in closed boarding management schools. The main problems in closed boarding management schools were the excessively low percentage of energy from carbohydrates and the excessively high percentage of energy from fat. Both deficiency and excess energy supply ratios of protein, carbohydrate, and fat were present in semi-closed boarding management schools. There was a high risk of calcium, iron, zinc, magnesium, and selenium deficiency for most students in both management schools. The closed-school girls had the highest risk of suffering from iron deficiency. Vitamin A, vitamin B1, vitamin B2, vitamin C, and vitamin E deficiencies were severe in both schools, especially vitamin C, vitamin A, and vitamin B2 deficiencies in semi-closed boarding management schoolboys. Effective nutritional interventions should be taken to improve the nutritional status of both boarding management and school students.

Idiopathic short stature and scoliosis in children treated with growth hormone.

The prevalence of scoliosis is not known in patients with idiopathic short stature, and the impact of treatment with recombinant human growth hormone on those with scoliosis remains controversial. We investigated the prevalence of scoliosis radiologically in children with idiopathic short stature, and the impact of treatment with growth hormone in a cross-sectional and retrospective cohort study. A total of 2,053 children with idiopathic short stature and 4,106 age- and sex-matched (1:2) children without short stature with available whole-spine radiographs were enrolled in the cross-sectional study. Among them, 1,056 with idiopathic short stature and 790 controls who had radiographs more than twice were recruited to assess the development and progression of scoliosis, and the need for bracing and surgery. In the cross-sectional study, there was an unexpectedly higher prevalence of scoliosis (33.1% (681/2,053) vs 8.52% (350/4,106)) in children with idiopathic short stature compared with controls (odds ratio 3.722; p < 0.001), although most cases were mild. In the longitudinal study, children with idiopathic short stature had a higher risk of the development and progression of scoliosis than the controls. Among children with idiopathic short stature without scoliosis at baseline, treatment with growth hormone significantly increased the risk of developing scoliosis (p = 0.015) and the need for bracing (p < 0.001). Among those with idiopathic short stature and scoliosis at baseline, treatment with growth hormone did not increase the risk of progression of the scoliosis, the need for bracing, or surgery. The impact of treatment with growth hormone on scoliosis in children with idiopathic short stature was considered controllable. However, physicians should pay close attention to the assessment of spinal curves in these children.

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.

Comparative Pharmacokinetic Study of Three Major Bioactive Components in the Normal and Different Courses of Liver-Stagnation and Spleen-Deficiency Syndrome Depressive Rats after Intragastric Administration of Zhi-Zi-Hou-Po Decoction.

To reveal the pharmacokinetic process of narirutin, naringin, and honokiol in normal and different courses of liver-stagnation and spleen-deficiency syndrome depressive rats after intragastric administration of Zhi-Zi-Hou-Po decoction (ZZHPD), a rapid ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) method was proposed in this study. Chronic unpredictable mild stress (CUMS) rat was employed as the depression model. Acetonitrile solution containing 0.1% acetic acid and methyl alcohol-water (50 : 50, v/v) was chosen as the protein precipitant and redissolve solution severally; a Shim-pack GISS C18 column coupled with 0.1% aqueous acetic acid-acetonitrile in gradient elution was employed to separate the mixed constituents in plasma. The WinNonLin software (version 6.1) was chosen as the analytical tool for the pharmacokinetic parameters. The results indicated that compared with rats in the control group, the sucrose preference, scores in the open-field test, and the concentration of 5-HT in plasma of rats in CUMS and CUMS + ZZHPD treatment groups were lower, while the immobility time in the forced swimming test of rats in these two groups was longer, which implied that the depression model was successful. These behavioral and biochemical indexes of rats above in the CUMS + ZZHPD treatment group were improved after oral administration of ZZHPD, which indicated that the antidepressant effect of ZZHPD was definite. The UHPLC-MS/MS method was stabilized, sensitive, and exclusive, and the extraction recovery and matrix effect of three analytes were all above 89%. The T max, AUC, and Cmax of three ingredients in CUMS-induced depression rats were significantly larger than control rats, while these pharmacokinetic parameters in CUMS + ZZHPD treatment rats were decreased significantly compared with CUMS-induced depression rats, which may relate with the changes in physiological function of the gastrointestinal tract and liver in CUMS-induced liver-stagnation and spleen-deficiency syndrome depressive rats. This study provided important information for the clinical rational use of ZZHPD in antidepressant treatment.

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.

Anterior decompression through transoral axis slide and rotation osteotomy for salvage of failed posterior occipitocervical fusion: a novel technique note.

Atlantoaxial dislocation could be caused by odontoid fractures or Os odontoideum. The previous surgical techniques in treatment of atlantoaxial dislocation were based on arch remove decompression or anterior atlantoaxial release and atlantoaxial (occipital-cervical) screw fixation-based reduction and fusion. However, for some clinical situations, all of above techniques cannot be applied. In this study, a patient with atlantoaxial dislocation caused by Os odontoideum treated by posterior occipitocervical fusion 20 years ago and failed. We design a novel anterior decompression through transoral axis slide and rotation osteotomy for salvage of this failed posterior occipitocervical fusion case. The C2 body and odontoid process was ventrally slide and rotation at good position after operation as well as the position of plate and screws, the spinal canal was increased significantly after operation too. We suggest this anterior decompression through transoral "C2 slide and rotation" technique is good choice for salvage of failed posterior occipitocervical fusion and some irreducible atlantoaxial dislocation because of the anterior bony fusion, it could direct decompress the spinal cord anteriorly, avoid the odontoid resection, and is feasible and safe technique.

Dual regulation of microglia and neurons by Astragaloside IV-mediated mTORC1 suppression promotes functional recovery after acute spinal cord injury.

Inflammation and neuronal apoptosis contribute to the progression of secondary injury after spinal cord injury (SCI) and are targets for SCI therapy; autophagy is reported to suppress apoptosis in neuronal cells and M2 polarization may attenuate inflammatory response in microglia, while both are negatively regulated by mTORC1 signalling. We hypothesize that mTORC1 suppression may have dual effects on inflammation and neuronal apoptosis and may be a feasible approach for SCI therapy. In this study, we evaluate a novel inhibitor of mTORC1 signalling, Astragaloside IV (AS-IV), in vitro and in vivo. Our results showed that AS-IV may suppress mTORC1 signalling both in neuronal cells and microglial cells in vitro and in vivo. AS-IV treatment may stimulate autophagy in neuronal cells and protect them against apoptosis through autophagy regulation; it may also promote M2 polarization in microglial cells and attenuate neuroinflammation. In vivo, rats were intraperitoneally injected with AS-IV (10 mg/kg/d) after SCI, behavioural and histological evaluations showed that AS-IV may promote functional recovery in rats after SCI. We propose that mTORC1 suppression may attenuate both microglial inflammatory response and neuronal apoptosis and promote functional recovery after SCI, while AS-IV may become a novel therapeutic medicine for SCI.

The homogeneous and heterogeneous risk factors for occurrence and prognosis in lung cancer patients with bone metastasis.

PURPOSE: To analyse the homogeneous and heterogeneous risk factors for occurrence and prognosis in lung cancer patients diagnosed with bone metastasis (BM) by using the Surveillance, Epidemiology, and End Results (SEER) database. PATIENTS AND METHODS: The medical records of lung cancer patients with or without bone metastasis were identified in the SEER database between 2010 and 2015. A multivariate logistic regression analysis was performed to identify risk factors, and a multivariate Cox regression was used to determine the prognostic effects of every variable on survival. RESULTS: In total, 34,585 eligible patients from the SEER database were included in the analysis. Male gender and metastasis to the liver were factors that were both positively associated with a risk for the development and prognosis of bone metastasis in patients with lung cancer. Younger age, poor tumour differentiation grade, higher N stage (N3), adenocarcinoma and metastasis to the brain were all positively correlated with a risk of occurrence of BM, but these factors were not correlated with an unfavourable prognosis. Age, race, marital status, tumour size and pathologic type were independent risk factors for the prognosis of bone metastasis. CONCLUSION: The morbidity of bone metastasis in lung cancer patients is dismal, with a rate of 25.9%. The findings of this study estimate the homogeneous and heterogeneous risk factors for the occurrence and prognosis of bone metastasis in lung cancer patients, which may provide clinical guidelines for physicians.

Activation of Nrf2/HO-1 signal with Myricetin for attenuating ECM degradation in human chondrocytes and ameliorating the murine osteoarthritis.

BACKGROUND: Osteoarthritis (OA), one of the prevailing joint degenerative disorders, contributes to the disability around the world. However, no effective therapeutic was introduced currently. Myricetin was reported to possess the function of anti-inflammatory, anti-diabetic and anti-cancer. Thus, we investigate the protection role of myricetin in OA progression and the potential molecular mechanism in present study. METHODS: Quantitative realtime PCR and western blotting were performed to evaluate the expression of MMP-13, Aggrecan, iNOS, and COX-2 at both gene and protein levels. An enzyme-linked immunosorbent assay was used to evaluate the levels of inflammatory factors (PGE2, TNF-α, and IL-6). The PI3K/AKT, Nrf2/HO-1 and nuclear factor kappa B (NF-κB) signaling pathways were analyzed by western blotting, and immunofluorescence was used to assess the expression of Nrf2, Collagen II and MMP13. The in vitro effect of myricetin was evaluated by intragastric administration into a mouse osteoarthritis model induced by destabilization of the medial meniscus. RESULTS: Myricetin not only inhibited the generation of inflammatory mediators and cytokines such as nitric oxide (NO), prostaglandin E2 (PGE2), TNF-α and IL-6, but also suppressed the production of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in human chondrocytes under IL-1ß stimulation. Moreover, Metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS5), which resulted in the degradation of cartilage, were also suppressed in chondrocytes with the treatment of myricetin. To explore the potential mechanism, we found out that myricetin suppressed NF-κB signaling pathway through Nrf2/HO-1 axis in human chondrocytes. Besides, myricetin regulated the Nrf2 signaling pathway through PI3K/Akt pathway. In addition, in vivo study demonstrated that myricetin could ameliorated the progression of OA in mice DMM model through PI3K/Akt mediated Nrf2 signaling pathway. CONCLUSION: Taken together, our data first demonstrated that myricetin possesses the therapeutic potential on OA through PI3K/Akt mediated Nrf2/HO-1 signaling pathway.

Baicalein Inhibits the IL-1ß-Induced Inflammatory Response in Nucleus Pulposus Cells and Attenuates Disc Degeneration In vivo.

Intervertebral disc degeneration (IDD) is widely considered one of the main causes of low back pain, which is a chronic progressive disease closely related to inflammation and degeneration of nucleus pulposus (NP) cells. Baicalein is a natural bioactive compound with anti-inflammatory effects in different diseases, including inhibition of the inflammatory response in chondrocytes, whose morphology and avascular supply are similar to those of NP cells. Therefore, we hypothesized that baicalein may have a therapeutic effect on IDD by suppressing the inflammatory response. In vitro, NP cells were pretreated with baicalein for 2 h and then incubated with IL-1ß for 24 h. We found that baicalein not only inhibited the overexpression of inflammatory cytokine production, including NO, PGE2, TNF-α, and IL-6, but also suppressed the expression of COX-2 and iNOS. The IL-1ß-induced overexpression of MMP13 and ADAMTS5 and degradation of aggrecan and type II collagen were reversed by baicalein in a dose-dependent manner. Mechanistically, we found that baicalein suppressed the IL-1ß-induced activation of the NF-κB and MAPK pathways. Moreover, an in vivo study demonstrated that baicalein treatment could ameliorate IDD in a puncture-induced rat model. Thus, baicalein has great value as a potential therapeutic agent for IDD.

Factors Associated with Cervical Spine Alignment in an Asymptomatic Population: A Preliminary Analysis.

BACKGROUND: Cervical sagittal imbalance compromises health-related quality of life and can lead to myriad incapacitating symptoms through compression of the spinal cord. Questions regarding which parameters play primary roles in the progression of cervical sagittal imbalance and which might be compensatory factors remain unanswered. METHODS: This study enrolled 246 asymptomatic volunteers from July 2016 to June 2018. After demographic and radiologic parameters were measured, the data were analyzed using correlation coefficient test and multiple regression analysis. A predictive equation was assessed with variance analysis, residual analysis, collinearity analysis, and a paired t test. RESULTS: Average values are as follows: orbital tilt, 64 ± 6°; orbital slope (OS), 15 ± 6°; C0-C2 lordosis (C0C2), 28 ± 8°; cervical lordosis (CL), 5 ± 11°; C2-C7 sagittal vertical axis (C2C7SVA), 15 ± 8 mm; T1 slope (TS), 17 ± 6°; thoracic inlet angle, 69 ± 8°; thoracic kyphosis, 34 ± 9°; lumbar lordosis, 50 ± 10°; sacral slope, 38 ± 7°; pelvic index, 48 ± 9°; sagittal vertical axis, 10 ± 19 mm. Correlations of C2C7SVA were observed with body mass index (BMI), OS, C0C2, CL, and TS. The validated predictive equation was: C2C7SVA = 0.38 × BMI - 0.73 × OS + 0.73 × C0C2 + 0.15 × CL + 0.18 × TS - 6.53. CONCLUSIONS: BMI, OS, C0C2, CL, and TS were primary influencers in the progression of cervical sagittal imbalance and established a predictive equation of asymptomatic population, which can provide clinical advice and remind surgeons of the primary influencers of reconstructive surgery for better prognoses.

[Protective effects of deep sea water against subacute alcoholic liver injury].

OBJECTIVE: To study the protective effects of two deep sea water( DSW)samples with different ion concentration against sub-acute alcoholic liver injury. METHODS: A total of 72 male KM mice( 18-22 g) were randomly assigned into six groups, i. e. the control group, model group, DSW-A1 fold concentration group( A1), DSW-A5 folds concentration group( A5), DSW-A 10 folds concentration group( A10), DSW-B5 fold concentration group( B). The corresponding DSW solution was ingested freely by each DSW group, and deionized water was ingested freely by the other two groups. The total administration duration was 30 consecutive days. Groups were given 50% ethanol solution( 0. 10 m L/10( g·d)) by ig since the 15 th day except the control group. After administration period, detect serum aspartate aminotransferase( AST), alanine aminotransferase( ALT), total bilirubin( T-BIL), total cholesterol( TC), triglyceride( TG) and low density lipoprotein( LDL), liver TC, TG, GSH, malonaldehyde( MDA), glutathione/glutathione oxidized( GSH/GSSG), superoxide dismutase( SOD), glutathione peroxidase( GSH-Px), catalase( CAT), xanthine oxidase( XOD). Livers were also further detected by microscopic examinations. RESULTS: Compared with the control group, the model group had serious liver steatosis. The histological score and serum T-BIL were significantly increased( P < 0. 01), serum TC, LDL, AST and liver MDA were significantly increased( P < 0. 05), liver GSH-Px was significantly decreased( P < 0. 01). Compared with the model group, in A1 group, the serum T-BIL was significantly decreased( P < 0. 05), liver GSH-Px( P < 0. 01) and XOD( P < 0. 05) were significantly increased. In A5 group, serum T-BIL, liver MDA and pathologic changes were significantly decreased( P < 0. 01), serum TG and TC were significantly decreased( P <0. 05), liver GSH( P < 0. 01), GSH/GSSG( P < 0. 05), GSH-Px( P < 0. 01) and XOD( P < 0. 01) were significantly increased. In A10 group, serum LDL and AST were significantly decreased( P < 0. 05), serum TG, TC, T-BIL, liver MDA and the pathologic changes were significantly decreased( P < 0. 01), liver GSH/GSSG( P < 0. 05) and GSHPx( P < 0. 01) were significantly increased. In B group, serum TC and liver MDA were significantly decreased( P < 0. 05), serum TG, T-BIL, AST and liver pathologic changes were significantly decreased( P < 0. 01), liver XOD( P < 0. 05) and GSH-Px( P< 0. 01) were significantly increased. CONCLUSION: Middle and high concentration DSWA and DSW-B have protective effects against sub-acute alcoholic liver injury by decreasing serum lipid level, and improving the ability of antioxidation.

Small molecule natural compound agonist of SIRT3 as a therapeutic target for the treatment of intervertebral disc degeneration.

Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of intervertebral disc degeneration (IVDD). Sirtuin 3 (SIRT3), a sirtuin family protein located in mitochondria, is essential for mitochondrial homeostasis; however, the role of SIRT3 in the process of IVDD has remained elusive. Here, we explored the expression of SIRT3 in IVDD in vivo and in vitro; we also explored the role of SIRT3 in senescence, apoptosis, and mitochondrial homeostasis under oxidative stress. We subsequently activated SIRT3 using honokiol to evaluate its therapeutic potential for IVDD. We assessed SIRT3 expression in degenerative nucleus pulposus (NP) tissues and oxidative stress-induced nucleus pulposus cells (NPCs). SIRT3 was knocked down by lentivirus and activated by honokiol to determine its role in oxidative stress-induced NPCs. The mechanism by which honokiol affected SIRT3 regulation was investigated in vitro, and the therapeutic potential of honokiol was assessed in vitro and in vivo. We found that the expression of SIRT3 decreased with IVDD, and SIRT3 knockdown reduced the tolerance of NPCs to oxidative stress. Honokiol (10 µM) improved the viability of NPCs under oxidative stress and promoted their properties of anti-oxidation, mitochondrial dynamics and mitophagy in a SIRT3-dependent manner. Furthermore, honokiol activated SIRT3 through the AMPK-PGC-1α signaling pathway. Moreover, honokiol treatment ameliorated IVDD in rats. Our study indicated that SIRT3 is involved in IVDD and showed the potential of the SIRT3 agonist honokiol for the treatment of IVDD.

SIRT3 Activation by Dihydromyricetin Suppresses Chondrocytes Degeneration via Maintaining Mitochondrial Homeostasis.

Mitochondrial dysfunction is an important contributor to the development of osteoarthritis (OA). Sirtuin 3 (SIRT3) regulates diverse mitochondrial proteins to maintain mitochondrial homeostasis, and dihydromyricetin (DHM) is reported as a potential SIRT3 activator. This study aims to explore the relevance of SIRT3 and OA, as well as the therapeutic effects of DHM on mitochondrial homeostasis in TNF-α-treated chondrocytes. The relationship between SIRT3 and OA was confirmed by detecting SIRT3 level in vitro and in vivo. Mitochondrial dysfunction was evaluated in chondrocytes with or without SIRT3 knockdown. Furthermore, the effects of DHM on mitochondrial homeostasis were performed in TNF-α-treated rat chondrocytes in vitro. In this study, our results showed that the SIRT3 level was decreased in mouse OA cartilage, corresponding to the reduced SIRT3 level in TNF-α-treated chondrocytes in vitro. SIRT3 knockdown induced mitochondrial dysfunction in chondrocytes. Moreover, our study demonstrated that DHM might activate SIRT3 to protect rat chondrocytes from TNF-α-induced degeneration and protective effects of DHM on mitochondrial homeostasis in chondrocytes attributed to enhanced SIRT3. Collectively, SIRT3 deficiency is implicated in OA development and DHM exerts anti-degeneration effect by maintaining mitochondrial homeostasis via a SIRT3-dependent manner in chondrocytes.

Biomechanical properties of novel transpedicular transdiscal screw fixation with interbody arthrodesis technique in lumbar spine: A finite element study.

PURPOSE: The purpose of this study was to investigate finite element biomechanical properties of the novel transpedicular transdiscal (TPTD) screw fixation with interbody arthrodesis technique in lumbar spine. METHODS: An L4-L5 finite element model was established and validated. Then, two fixation models, TPTD screw system and bilateral pedicle screw system (BPSS), were established on the validated L4-L5 finite element model. The inferior surface of the L5 vertebra was set immobilised, and moment of 7.5 Nm was applied on the L4 vertebra to test the range of motion (ROM) and stress at flexion, extension, lateral bending and axial rotation. RESULTS: The intact model was validated for prediction accuracy by comparing two previously published studies. Both of TPTD and BPSS fixation models displayed decreased motion at L4-L5. The ROMs of six moments of flexion, extension, left lateral bending, right lateral bending, left axial rotation and right axial rotation in TPTD model were 1.92, 2.12, 1.10, 1.11, 0.90 and 0.87°, respectively; in BPSS model, they were 1.48, 0.42, 0.35, 0.38, 0.74 and 0.75°, respectively. The screws' peak stress of above six moments in TPTD model was 182.58, 272.75, 133.01, 137.36, 155.48 and 150.50 MPa, respectively; and in BPSS model, it was 103.16, 129.74, 120.28, 134.62, 180.84 and 169.76 MPa, respectively. CONCLUSION: Both BPSS and TPTD can provide stable biomechanical properties for lumbar spine. The decreased ROM of flexion, extension and lateral bending was slightly more in BPSS model than in TPTD model, but TPTD model had similar ROM of axial rotation with BPSS model. The screws' peak stress of TPTD screw focused on the L4-L5 intervertebral space region, and more caution should be put at this site for the fatigue breakage. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our finite element study provides the biomechanical properties of novel TPTD screw fixation, and promotes this novel transpedicular transdiscal screw fixation with interbody arthrodesis technique be used clinically.

Polydatin suppresses nucleus pulposus cell senescence, promotes matrix homeostasis and attenuates intervertebral disc degeneration in rats.

Intervertebral disc degeneration (IVDD) is one of the major causes of low back pain. Polydatin (PD) has been shown to exert multiple pharmacological effects on different diseases; here, we test the therapeutic potential of PD for IVDD. In in-vitro experiments, we confirmed PD is nontoxic to nucleus pulposus cells (NPCs) under the concentration of 400 µmol/L. Furthermore, PD was able to decrease the level of senescence in TNF-α-treated NPCs, as indicated by ß-gal staining as well as senescence markers p53 and p16 expression. In the aspect of extracellular matrix (ECM), PD not only reduced metalloproteinase 3 (MMP-3), metalloproteinase 13 (MMP-13) and a disintegrin-like and metalloproteinase thrombospondin type 1 motif 4 (ADAMTS-4) expression, but also increased aggrecan and collagen II levels. Mitochondrion is closely related to cellular senescence and ECM homeostasis; mechanistically, we found PD may rescue TNF-α-induced mitochondrial dysfunction, and it may also promote Nrf2 expression and activity. Silencing Nrf2 partly abolished the protective effects of PD on mitochondrial homeostasis, senescence and ECM homeostasis in TNF-α-treated NPCs. Correspondingly, PD ameliorated IVDD in rat model by promoting Nrf2 activity, preserving ECM and inhibiting senescence in nucleus pulposus cells. To sum up, our study suggests that PD exerts protective effects in NPCs against IVDD and reveals the underlying mechanism of PD on Nrf2 activation in NPCs.

Acceptable Chin-Brow Vertical Angle for Neutral Position Radiography: Preliminary Analyses Based on Parameters of the Whole Sagittal Spine of an Asymptomatic Chinese Population.

OBJECTIVE: We sought to acquire the whole sagittal spine parameters and investigated the acceptable chin-brow vertical angle (CBVA) for neutral position radiography in an asymptomatic Chinese population. METHODS: The parameters measured in 257 asymptomatic volunteers included CBVA, occipital slope, orbital tilt, occipital incidence, C0-C2 Cobb angle, C2-C7 Cobb angle, C1-C7 Cobb angle, C2-C7 sagittal vertical axis and absolute rotation angle, cervical tilt, cranial tilt, T1 slope, and thoracic kyphosis, and others. We used Pearson correlation analyses to find relationships between CBVA and other variables. The subjects were divided into 5 groups according to the CBVA percentile: group A, 0%-20% CBVA; group B, 20%-40% CBVA; group C, 40%-60% CBVA; group D, 60%-80% CBVA; and group E, 80%-100% CBVA. We used analysis of variance to analyze differences among the 5 groups. RESULTS: Orbital tilt, Occipital incidence, C1-C7 Cobb angle, C2-C7 sagittal vertical axis, and cranial tilt all increased with increasing CBVA (P < 0.001). The occipital slope, C2-C7 Cobb angle, C2-C7 absolute rotation angle, cervical tilt, T1 slope, and thoracic kyphosis decreased with decreasing CBVA (P < 0.05). No correlations between other sagittal parameters and the CBVA were found. A slight deviation was found in groups B-D, with a greater deviation in groups A, C, and E. CONCLUSIONS: An acceptable range of -1.5° to 5.8° is recommended for the CBVA for cervical radiography in the neutral position. When spinal surgeons evaluate the cervical plane, the effects of the CBVA deviation on cervical curvature must be considered.

Rate of presence of 11 thoracic vertebrae and 6 lumbar vertebrae in asymptomatic Chinese adult volunteers.

BACKGROUND: An increasing number of studies on spinal morphology in asymptomatic Asian and Western patients have been reported. Variation in spinal anatomy among patients is considered as the cause of wrong-level surgery in up to 40% of cases. The present study examined the rate of presence of 11 thoracic vertebrae and 6 lumbar vertebrae in 293 asymptomatic Chinese adult volunteers. METHODS: From May 27, 2016, to November 11, 2017, a cohort of 325 asymptomatic Chinese adults meeting the study exclusion criteria was recruited. The radiographs were examined by a spine surgeon and a radiologist to assess the number of thoracic and lumbar vertebrae. RESULTS: In total, 293 volunteers were included in this study: 17 (5.8%) had 11 thoracic vertebrae, and 16 (5.5%) had 6 lumbar vertebrae. Among all volunteers, 12 (4.1%) had 7 cervical vertebrae (C), 11 thoracic vertebrae (T), and 5 lumbar vertebrae (L); 5 (1.7%) had 7C, 11T, and 6L; and 11 (3.8%) had 7C, 12T, and 6L. There was no difference between the findings of the spine surgeon and the radiologist. CONCLUSIONS: For the first time, this study describes the rate of presence of 11 thoracic vertebrae and 6 lumbar vertebrae in 293 asymptomatic Chinese adult volunteers. Variations in the number of thoracic and lumbar vertebrae tend to be ignored by spine surgeons. We encourage spinal surgeons and researchers to be aware of such variations when performing thoracic- and lumbar-level surgery and assessing spinal alignment and parameters.

Does the Iliac Wing Influence L5 Pedicle Screw Fixation?

OBJECTIVE: To explore whether the iliac wing influences L5 pedicle screw (PS) fixation and to propose methods to reduce such influence. METHODS: A total of 100 computed tomography scans (from 50 male and 50 female patients) of the lower lumbar region and pelvis were obtained and 3-dimensionally reconstructed. Cylinders with 6.5-mm diameters were drawn to simulate the different trajectories of L5 PS. The maximum lengths and lateral angles of trajectories, and the vertical distances from the inner edge of the iliac wing to these trajectories, were measured. RESULTS: The maximum lengths and lateral angles differed significantly among trajectories; the maximum length, but not the lateral angle, differed significantly between male and female subjects. The influence of the iliac wing was more significant in male than in female subjects. The iliac wing had a greater effect on screws implanted along the pedicle axis than on screws for which the trajectories commenced at Du's entry point and passed through the center of the pedicle. CONCLUSIONS: This study elucidates the influence of the iliac wing on L5 PS fixation. Careful attention is required when implanting PSs, especially in male patients. The combined use of Du's technique and a percutaneous method for PS implantation effectively reduces the influence of the iliac wing. To minimize the complications of PS fixation further, preoperative simulation of fixation for each patient is very important.