Assessing Cross-Cultural Adaptation of the Spine Oncology Study Group Outcomes Questionnaire 2.0: A Methodological Systematic Review Regard to Consensus-Based Standards for the Selection of Health Measurement Instruments Guideline.

STUDY DESIGN: systematic review of cross-cultural adaptation. OBJECTIVES: SOSGOQ 2.0 was widely used to assess the HRQQOL of patients with spinal metastasis. Due to the lack of methodological quality assessment, it is a challenge to use the questionnaire in routine practice. This study aims to comprehensively evaluate the translation procedures and measurement attributes of SOSGOQ 2.0 according to COSMIN guidelines. METHODS: The literature was reviewed adhering to the PRISMA guidelines. Each translation process and different cultural adaptation methods were classified according to the guidelines for Cross cultural Adaptation Process of Self Reporting Measures, and the methodological quality of the identified research was evaluated according to the consensus based on the selection criteria of health measurement tools. RESULTS: 6 publications finally met the inclusion criteria. As for the evaluation of translation procedures and cross-cultural adaptability, two adaptations did not report the detailed information in translation and cross-cultural adaptation (synthesis, back translation, review by expert committee, pre-test), factor analysis and sample size calculation were only mentioned in two studies, and only one adaptation met the minimum sample size standard. Regard to the methodological quality assessment of measurement attributes, all adaptations completed internal consistency, structural effectiveness and reliability. However, none of the adaptations reported measurement errors and only one reported response sensitivity. CONCLUSIONS: We found that the methodological quality of the current adaptation was uneven, and the report of measurement attribute results was not comprehensive. We recommend higher quality German, Italian and Chinese adaptation.

Changes in brain functional networks in remitted major depressive disorder: a six-month follow-up study.

BACKGROUND: Patients with remitted major depressive disorder (rMDD) show abnormal functional connectivity of the central executive network (CEN), salience networks (SN) and default mode network (DMN). It is unclear how these change during remission, or whether changes are related to function. METHODS: Three spatial networks in 17 patients with rMDD were compared between baseline and the six-month follow-up, and to 22 healthy controls. Correlations between these changes and psychosocial functioning were also assessed. RESULTS: In the CEN, patients at baseline had abnormal functional connectivity in the right anterior cingulate, right dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobule (IPL) compare with HCs. There were functional connection differences in the right DLPFC and left IPL at baseline during follow-up. Abnormal connectivity in the right DLPFC and medial prefrontal cortex (mPFC) were found at follow-up. In the SN, patients at baseline had abnormal functional connectivity in the insula, left anterior cingulate, left IPL, and right precuneus; compared with baseline, patients had higher connectivity in the right DLPFC at follow-up. In the DMN, patients at baseline had abnormal functional connectivity in the right mPFC. Resting-state functional connectivity of the IPL and DLPFC in the CEN correlated with psychosocial functioning. CONCLUSIONS: At six-month follow-up, the CEN still showed abnormal functional connectivity in those with rMDD, while anomalies in the SN and DMN has disappeared. Resting-state functional connectivity of the CEN during early rMDD is associated with psychosocial function. CLINICAL TRIALS REGISTRATION: Pharmacotherapy and Psychotherapy for MDD after Remission on Psychology and Neuroimaging. https://www. CLINICALTRIALS: gov/ , registration number: NCT01831440 (15/4/2013).

Altered brain function in patients with acrophobia: A voxel-wise degree centrality analysis.

AIM: To explore the local spontaneous neural activity and whole-brain functional connectivity patterns in the resting brain of acrophobia patients. METHODS: 50 patients with acrophobia and 47 healthy controls were selected for this study. All participants underwent resting-state MRI scans after enrollment. The imaging data were then analyzed using a voxel-based degree centrality (DC) method, and seed-based functional connectivity (FC) correlation analysis was used to explore the correlation between abnormal functional connectivity and clinical symptom scales in acrophobia. The severity of symptoms was evaluated using self-report and behavioral measures. RESULTS: Compared to controls, acrophobia patients showed higher DC in the right cuneus and left middle occipital gyrus and significantly lower DC in the right cerebellum and left orbitofrontal cortex (p < 0.01, GRF corrected). Additionally, there were negative correlations between the acrophobia questionnaire avoidance (AQ- Avoidance) scores and right cerebellum-left perirhinal cortex FC (r = -0.317, p = 0.025) and between scores of the 7-item generalized anxiety disorder scale and left middle occipital gyrus-right cuneus FC (r = -0.379, p = 0.007). In the acrophobia group, there was a positive correlation between behavioral avoidance scale and right cerebellum-right cuneus FC (r = 0.377, p = 0.007). CONCLUSIONS: The findings indicated that there are local abnormalities in spontaneous neural activity and functional connectivity in the visual cortex, cerebellum, and orbitofrontal cortex in patients with acrophobia.

Remission of symptoms is not equal to functional recovery: Psychosocial functioning impairment in major depression.

The ultimate goal of depression treatment is to achieve functional recovery. Psychosocial functioning is the main component of functional impairment in depressed patients. The concept of psychosocial functioning has an early origin; however, its concept and connotation are still ambiguous, which is the basic and key problem faced by the relevant research and clinical application. In this study, we start from the paradox of symptoms remission and functional recovery, describe the concept, connotation, and characteristics of psychosocial functioning impairment in depressed patients, and re-emphasize its importance in depression treatment to promote research and clinical applications related to psychosocial functioning impairment in depressed patients to achieve functional recovery.

Succinate induces skeletal muscle fiber remodeling via SUNCR1 signaling.

The conversion of skeletal muscle fiber from fast twitch to slow-twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber-type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss-of-function models generated by phospholipase Cß antagonists, SUNCR1 global knockout, or SUNCR1 gastrocnemius-specific knockdown, we found that the effects of succinate on skeletal muscle fiber-type remodeling are mediated by SUNCR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR1 signaling pathway. These findings suggest the potential beneficial use of succinate-based compounds in both athletic and sedentary populations.

The Dipeptide Pro-Gly Promotes IGF-1 Expression and Secretion in HepG2 and Female Mice via PepT1-JAK2/STAT5 Pathway.

It has been shown that IGF-1 secretion is influenced by dietary protein or amino acid. However, whether the dipeptides elicit regulatory effects on IGF-1 secretion remains largely unclear. Thus, this study aimed to investigate the effects of the dipeptide Pro-Gly on IGF-1 expression and secretion in HepG2 cells and mice, and explore the underlying mechanisms. The in vitro results indicated that Pro-Gly, but not Pro plus Gly, promoted the expression and secretion of IGF-1 in HepG2. Meanwhile, the expression of the peptide transporter 1 (PepT1) was elevated by Pro-Gly, whereas knockdown of PepT1 with siRNA eliminated the increase of IGF-1 expression induced by Pro-Gly. In addition, Pro-Gly activated JAK2/STAT5 signaling pathway in a PepT1-dependent manner. Furthermore, Pro-Gly enhanced the interaction between JAK2 and STAT5, and the translocation of phospho-STAT5 to nuclei. Moreover, inhibition of JAK2/STAT5 blocked the promotive effect of Pro-Gly on IGF-1 expression and secretion. In agreement with the in vitro results, the in vivo findings demonstrated that Pro-Gly, but not Pro plus Gly, stimulated the expression and secretion of IGF-1 and activated JAK2/STAT5 signaling pathway in the liver of mice injected with Pro-Gly or Pro+Gly acutely or chronically. Besides, acute injection of JAK2/STAT5 inhibitor abolished the elevation of IGF-1 expression and secretion induced by Pro-Gly in mice. Collectively, these findings suggested that the dipeptide Pro-Gly promoted IGF-1 expression and secretion in HepG2 cells and mice by activating JAK2/STAT5 signaling pathway through PepT1. These data provided new insights to the regulation of IGF-1 expression and secretion by the dipeptides.

Arginine reverses growth hormone resistance through the inhibition of toll-like receptor 4-mediated inflammatory pathway.

OBJECTIVE: Growth hormone stimulates growth by increasing insulin-like growth factor 1 expression and secretion. In the presence of insufficient nutrients, GH increases, whereas IGF-1 expression becomes severely suppressed, leading to GH resistance. This study aimed to explore the effect of arginine (Arg) on GH resistance during malnutrition and to describe its underlying mechanism. METHODS: C57BL/6J mice were injected intraperitoneally with Arg for 1h or subjected to caloric restriction with Arg supplement in drinking water for 18days. HepG2 cells were exposed to different Arg concentrations for 24h. Signaling pathway agonists/inhibitors, siRNA, and overexpression plasmids were used to investigate the underlying molecular mechanism. Liver-specific toll-like receptor (TLR4) knockout mice were utilized to clarify the role of TLR4 in Arg-induced IGF-I expression and secretion. RESULTS: Arg inhibited the TLR4 downstream pathway by binding to TLR4 and consequently activated Janus kinase 2/signal transducer and activator of transcription 5 signaling pathway. As a result, IGF-1 transcription and secretion increased. Arg activity was absent in liver-specific TLR4 knockout mice and was greatly suppressed in liver with overexpressed TLR4, suggesting that hepatic TLR4 was required and sufficient to induce GH resistance. By contrast, the mammalian target of rapamycin pathway was unnecessary for Arg activity. Arg not only significantly increased IGF-1 expression and secretion under acute fasting and chronic CR conditions but also attenuated body weight loss. CONCLUSIONS: Our results demonstrate a previously unappreciated pathway involving Arg that reverses GH resistance and alleviates malnutrition-induced growth restriction through the inhibition of TLR4-mediated inflammatory pathway.

Laminarin counteracts diet-induced obesity associated with glucagon-like peptide-1 secretion.

Laminarin, a type of ß-glucan isolated from brown seaweeds, exhibits verity of physiological activities, which include immunology modulation and antitumor function. To investigate the effect of laminarin on energy homeostasis, mice were orally administrated with laminarin to test food intake, fat deposition, and glucose homeostasis. Chronically, laminarin treatment significantly decreases high-fat-diet-induced body weight gain and fat deposition and reduces blood glucose level and glucose tolerance. Acutely, laminarin enhances serum glucagon-like peptide-1 (GLP-1) content and the mRNA expression level of proglucagon and prohormone convertase 1 in ileum. Subsequently, laminarin suppresses the food intake of mice, the hypothalamic AgRP neuron activity, and AgRP expression but activates pancreatic function. Furthermore, laminarin-induced appetite reduction was totally blocked by Exendin (9-39), a specific competitive inhibitor of GLP-1 receptor. Then, STC-1 cells were adopted to address the underlying mechanism, by which laminarin promoted GLP-1 secretion in vitro. Results showed that laminarin dose-dependently promoted GLP-1 secretion and c-Fos protein expression in STC-1 cells, which were independent of Dectin-1 and CD18. Interestingly, BAPTA-AM, a calcium-chelating agent, potently attenuated laminarin-induced [Ca2+]i elevation, c-Fos expression, and GLP-1 secretion. In summary, our data support that laminarin counteracts diet-induced obesity and stimulates GLP-1 secretion via [Ca2+]i; this finding provides an experimental basis for laminarin application to treat obesity and maintain glucose homeostasis.

Succinate promotes skeletal muscle protein synthesis via Erk1/2 signaling pathway.

It is well known that endurance training is effective to attenuate skeletal muscle atrophy. Succinate is a typical TCA metabolite, of which exercise could dramatically increase the content. The present study aimed to investigate the effect of succinate on protein synthesis in skeletal muscle, and try to delineate the underlying mechanism. The in vitro study revealed that succinate dose­dependently increased protein synthesis in C2C12 myotube along with the enhancement of phosphorylation levels of AKT Serine/Threonine Kinase 1(Akt), mammalian target of rapamycin, S6, eukaryotic translation initiation factor 4E, 4E binding protein 1 and forkhead box O (FoxO) 3a. Furthermore, it was demonstrated that 20 mM succinate markedly increased [Ca2+]i. Then, the phospho­extracellular regulated kinase (Erk), ­Akt level and the crosstalk between Erk and Akt were elevated in response to succinate. Notably, the Erk antagonist (U0126) or mTOR inhibitor (rapamycin) abolished the effect of succinate on protein synthesis. The in vivo study verified that succinate dose­dependently increased the protein synthesis, in addition to phosphorylation levels of Erk, Akt and FoxO3a in gastrocnemius muscle. In summary, these findings demonstrated that succinate promoted skeletal muscle protein deposition via Erk/Akt signaling pathway.

Dietary protein-induced hepatic IGF-1 secretion mediated by PPARγ activation.

Dietary protein or amino acid (AA) is a crucial nutritional factor to regulate hepatic insulin-like growth factor-1 (IGF-1) expression and secretion. However, the underlying intracellular mechanism by which dietary protein or AA induces IGF-1 expression remains unknown. We compared the IGF-1 gene expression and plasma IGF-1 level of pigs fed with normal crude protein (CP, 20%) and low-protein levels (LP, 14%). RNA sequencing (RNA-seq) was performed to detect transcript expression in the liver in response to dietary protein. The results showed that serum concentrations and mRNA levels of IGF-1 in the liver were higher in the CP group than in the LP group. RNA-seq analysis identified a total of 1319 differentially expressed transcripts (667 upregulated and 652 downregulated), among which the terms "oxidative phosphorylation", "ribosome", "gap junction", "PPAR signaling pathway", and "focal adhesion" were enriched. In addition, the porcine primary hepatocyte and HepG2 cell models also demonstrated that the mRNA and protein levels of IGF-1 and PPARγ increased with the increasing AA concentration in the culture. The PPARγ activator troglitazone increased IGF-1 gene expression and secretion in a dose dependent manner. Furthermore, inhibition of PPARγ effectively reversed the effects of the high AA concentration on the mRNA expression of IGF-1 and IGFBP-1 in HepG2 cells. Moreover, the protein levels of IGF-1 and PPARγ, as well as the phosphorylation of mTOR, significantly increased in HepG2 cells under high AA concentrations. mTOR phosphorylation can be decreased by the mTOR antagonist, rapamycin. The immunoprecipitation results also showed that high AA concentrations significantly increased the interaction of mTOR and PPARγ. In summary, PPARγ plays an important role in the regulation of IGF-1 secretion and gene expression in response to dietary protein.

The dipeptide Pro-Asp promotes IGF-1 secretion and expression in hepatocytes by enhancing JAK2/STAT5 signaling pathway.

It has been implicated that IGF-1 secretion can be regulated by dietary protein. However, whether the dipeptides, one of digested products of dietary protein, have influence on IGF-1 secretion remain largely unknown. Our study aimed to investigate the effects of the dipeptide Pro-Asp on IGF-1 secretion and expression in hepatocytes and to explore the possible underlying mechanisms. Our findings demonstrated that Pro-Asp promoted the secretion and gene expression of IGF-1 in HepG2 cells and primary porcine hepatocytes. Meanwhile, Pro-Asp activated the ERK and Akt signaling pathways, downstream of IGF-1. In addition, Pro-Asp enhanced GH-mediated JAK2/STAT5 signaling pathway, while inhibition of JAK2/STAT5 blocked the promotive effect of Pro-Asp on IGF-1 secretion and expression. Moreover, acute injection of Pro-Asp stimulated IGF-1 expression and activated JAK2/STAT5 signaling pathway in mice liver. Together, these results suggested that the dipeptide Pro-Asp promoted IGF-1 secretion and expression in hepatocytes by enhancing GH-mediated JAK2/STAT5 signaling pathway.

[Effects of comprehensive therapy on serum SPARC levels in ankylosing spondylitis patients accompanied with osteoporosis].

OBJECTIVE: To observe the effects of comprehensive therapy on serum secreted protein acidic and rich in cysteine (SPARC) levels in ankylosing spondylitis (AS) patients accompanied with osteoporosis (OP), and to explore the possible mechanisms for SPARC in AS patients accompanied with osteoporosis. METHODS: Totally 48 AS patients accompanied with OP (Group A) were treated with massage, intravenous infusion of Cervus and Cucumis Polypeptide Injection, and Bushen Quhan Zhiwang Decoction (BQZD) for 3 months. At the same time, 45 normal healthy subjects were recruited as the normal control group (Group B). Serum SPARC levels were measured by ELISA in Group A before and after comprehensive therapy and in those of Group B. The levels of bone mineral density of femoral neck (FN BMD), bone mineral density of 2 -4 lumbar spine (L2-4 BMD), bone specific alkaline phosphatase (BSAP), tumor necrosis factor alpha (TNF-alpha), and transforming growth factor beta-1 (TGF-beta1) were detected. Meanwhile, Bath AS disease activity index (BASDAI) and Bath AS functional index (BASFI) were detected in Group A before and after treatment. The correlations between the aforesaid indices and serum SPARC levels were analyzed. RESULTS: Serum SPARC levels were significantly lower in those of Group A than in those of Group B (175. 30 +/- 72.04 micro/L vs 190. 52 +/- 86. 13 microg/ L, P <0. 01). Serum SPARC levels in those of Group A were negatively correlated with TNF-alpha (r = -0.261, P <0.01), positively with L2-4 BMD, TGF-beta1, and BSAP (r =0.437,0.256, 0.385, P <0.05, P <0.01). L2-4BMD and BSAP were independently predictors of serum SPARC in patients of Group A. After comprehensive therapy, the levels of TNF-alpha, BASDAI, and BASFI obviously decreased, TGF-beta1, BSAP, L2-4 BMD, and FN BMD obviously increased (P <0. 05, P <0. 01). The serum SPARC levels also significantly increased (188.32 +/- 87.50 microg/L, P <0. 05). CONCLUSION: Comprehensive therapy could effectively improve the bone metabolism, clinical symptoms and the activity function of joints, and elevate serum SPARC levels.

Receptor for advanced glycation end products inhibits proliferation in osteoblast through suppression of Wnt, PI3K and ERK signaling.

Expression of receptor for advanced glycation end products (RAGE) plays a crucial role in bone metabolism. However, the role of RAGE in the control of osteoblast proliferation is not yet evaluated. In the present study, we demonstrate that RAGE overexpression inhibits osteoblast proliferation in vitro. The negative regulation of RAGE on cell proliferation results from suppression of Wnt, PI3K and ERK signaling, and is restored by RAGE neutralizing antibody. Prevention of Wnt signaling using Sfrp1 or DKK1 rescues RAGE-decreased PI3K and ERK signaling and cell proliferation, indicating that the altered cell growth in RAGE overexpressing cells is in part secondary to alterations in Wnt signaling. Consistently, RAGE overexpression inhibits the expression of Wnt targets cyclin D1 and c-myc, which is partially reversed by RAGE blockade. Overall, these results suggest that RAGE inhibits osteoblast proliferation via suppression of Wnt, PI3K and ERK signaling, which provides novel mechanisms by which RAGE regulates osteoblast growth.

[Effects of bushen tongdu decoction on serum tumor necrosis factor-alpha and transforming growth factor beta1, in patients with ankylosing spondylitis].

OBJECTIVE: To investigate the relationship of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor beta1 (TGF-beta1) with the occurrence of ankylosing spondylitis (AS), and the effects of Bushen Tongdu Decoction (BTD) on serum TNF-alpha and TGF-beta1, levels in patients. METHODS: Seventy five AS patients were assigned to two groups, 30 in the group I treated with Azulfidine and35 in the group II treated with BTD. ELISA was adopted to detect the levels of TNF-alpha and TGF-beta1, in patients before and after 24-week treatment. Meantime, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured as well. Besides, the levels of TNF-alpha and TGF-beta1 in 30 healthy persons were also detected for normal control. RESULTS: Before treatment, as compared with normal control, the TNF-alpha increased and TGF-beta1 decreased (P < 0.01) in the two treatment groups; the serum level of TNF-alpha was positively correlated with ESR and CRP (r = 0.296, r = 0.249; P < 0.05), but the serum level of TGF-beta1 showed no correlation with them (r = -0.222, r = -0.203; P > 0.05). After treatment, TGF-beta1 increased, while TNF-alpha, CRP and ESR decreased in group II (P < 0.01). CONCLUSION: BTD can regulate TNF-alpha and TGF-beta1 levels to suppress the immune inflammatory reaction so as to treat AS.