Trends in the distribution of socioeconomic inequalities in smoking and cessation: evidence among adults aged 18 ~ 59 from China Family Panel Studies data.

INTRODUCTION: Cigarette smoking is usually more prevalent among those with a lower socioeconomic status (SES), which can be driven by inequalities in the initiation and cessation of smoking, giving rise to SES disparities in health. This study aimed to gauge the SES inequalities in smoking related behaviours and their evolving trends based on a nationally representative database. METHOD: Data were extracted from repeated cross-sectional China Family Panel Studies (CFPS) of adults aged ≥18 and <60 years in 2012, 2014, 2016 and 2018. SES was constructed by principal component analysis based on income, education and occupation. Regression-based odds ratios and coefficients as the relative effect index of inequality were applied to quantify the degree of socioeconomic inequality in smoking related behaviours and to adjust for possible confounding factors. Multivariable regressions were utilized to explore the temporal trends in smoking inequalities. RESULTS: The smoking prevalence among men decreased from 61.16% to 2012 to 57.88% in 2018, cigarette consumption among current smokers declined from 16.71 to 15.49 cigs/per day, and the cessation rate increased from 17.55% to 24.08%. Cigarette consumption for women decreased from 13.39 in 2012 to 11.01 cigs/per day in 2018. Smoking prevalence showed significant SES inequalities among men and women from 2012 to 2018 (men: OR2012 (95%CI)= 0.72 (0.63, 0.83), OR2014 = 0.60 (0.52, 0.69), OR2016 = 0.58 (0.50, 0.67), OR2018 = 0.56 (0.48, 0.66); women: OR2012 = 0.63 (0.41, 0.97), OR2014 = 0.50 (0.32, 0.79), OR2016 = 0.44 (0.26,  0.73), OR2018 = 0.50 (0.30,  0.85)). Cigarette consumption showed significant SES inequalities among men from 2012 to 2018 (ß2012=-1.39 (-2.22, -0.57), ß2014=-2.37 (-3.23, -1.50), ß2016=-2.35 (-3.25, -1.44), ß2018=-2.91 (-3.86, -1.97)). In 2018, inequality emerged in smoking cessation rates among men and smoking intensity among women. However, all tests for trends in changes over time were not statistically significant (P varied from 0.072 to 0.602). CONCLUSION: The smoking prevalence declined between 2012 and 2018 in China. However, SES inequalities in smoking persist, while socioeconomic inequalities in smoking were not alleviated among adults aged 18 ~ 59 in China. Tobacco control measures should be implemented by giving more attention to people with lower SES who are more vulnerable to tobacco use.

Hydroxychloroquine/chloroquine and the risk of acute kidney injury in COVID-19 patients: a systematic review and meta-analysis.

OBJECTIVES: Hydroxychloroquine/chloroquine has been widely used as part of the standard treatment for patients with coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to determine whether hydroxychloroquine/chloroquine increases the risk of acute kidney injury (AKI) in COVID-19 patients. METHODS: PubMed and Embase were searched for related publications from inception to Dec 31, 2021, including randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) comparing the risk of AKI and/or increased creatinine in COVID-19 patients receiving hydroxychloroquine/chloroquine and other controls (active treatment and placebo). We conducted separate meta-analyses for RCTs and NRSIs based on fixed-effect model, with odds ratios (ORs) being considered as effect sizes. RESULTS: We included 21 studies in the analysis, with 12 were RCTs. Based on the RCTs, compared to placebo, the OR was 1.19 (95% confidence interval [CI]: 0.86, 1.64; p = .30, n = 4, moderate quality) for AKI and 1.00 (95%CI: 0.64, 1.56; p = .99, n = 5, moderate quality) for increased creatinine for patients received hydroxychloroquine/chloroquine treatment; compared to active treatment, the odds was 1.28 (95%CI: 0.65, 2.53; p = .47, n = 2, low quality) for AKI and 0.64 (95%CI: 0.13, 3.20; p = .59, n = 1, low quality) for increased creatine. Evidence from NRSIs showed slightly increased odds of AKI, with low quality. CONCLUSION: Based on current available studies which were graded as low to moderate quality, there is insufficient evidence to conclude that hydroxychloroquine/chloroquine use is associated with increased risk of AKI or raised creatinine. Abbreviations: AKI: acute kidney injury; COVID-19: Coronavirus Disease 2019; RCT: randomized controlled trials; NRSI: non-randomized studies of interventions; OR: odds ratios; ROBIS-I: Risk Of Bias In Non-randomized Studies - of Interventions.

Tenuigenin promotes the osteogenic differentiation of bone mesenchymal stem cells in vitro and in vivo.

Osteoporosis, which is a systemic skeletal disease characterized by low bone mineral density and microarchitectural deterioration of bone quality, is a global and increasing public health problem. Recent studies have suggested that Tenuigenin (TEN), a class of native compounds with numerous biological activities such as anti-resorptive properties, exerts protective effects against postmenopausal bone loss. The present study aims to investigate the osteogenic effects of TEN on bone mesenchymal stem cells (BMSCs) in vitro and in vivo. Alkaline phosphatase (ALP) activity/staining, Alizarin red staining and the expression of osteogenic markers, including runt-related transcription factor 2, osterix, osteocalcin, collagen Iα1, ß-catenin and glycogen synthase kinase-3ß were investigated in primary femoral BMSCs from C57/BL6 mice cultured under osteogenic conditions for 2 weeks to examine the effects of TEN. An ovariectomized (OVX) mouse model was used to investigate the effect of TEN treatment for 3 months in vivo. We found that ALP activity, mineralized nodules and the expression of osteogenic markers were increased and WNT/ß-catenin signaling was enhanced in vitro and in vivo. Bone parameters, including trabecular thickness, trabecular number and bone mineral density were higher in the OVX+TEN group than in control OVX mice. Our results suggest the therapeutic potential of TEN for the treatment of patients with postmenopausal osteoporosis.

Enhancement of the synthesis of n-3 PUFAs in fat-1 transgenic mice inhibits mTORC1 signalling and delays surgically induced osteoarthritis in comparison with wild-type mice.

BACKGROUND: An exogenous supplement of n-3 polyunsaturated fatty acids (PUFAs) has been reported to prevent osteoarthritis (OA) through undefined mechanisms. OBJECTIVE: This study investigated the effect of alterations in the composition of endogenous PUFAs on OA, and associations of PUFAs with mammalian target of rapamycin complex 1 (mTORC1) signalling, a critical autophagy pathway in fat-1 transgenic (TG) mice. METHODS: fat-1 TG and wild-type mice were used to create an OA model by resecting the medial meniscus. The composition of the endogenous PUFAs in mouse tissues was analysed by gas chromatography, and the incidence of OA was evaluated by micro-computed tomography (micro-CT), scanning electron microscopy and histological methods. Additionally, primary chondrocytes were isolated and cultured. The effect of exogenous and endogenous PUFAs on mTORC1 activity and autophagy in chondrocytes was assessed. RESULTS: The composition of endogenous PUFAs of TG mice was optimised both by increased n-3 PUFAs and decreased n-6 PUFAs, which significantly alleviated the articular cartilage destruction and osteophytosis in the OA model (p<0.01), decreased protein expression of matrix metalloproteinase-13 (MMP-13) and ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs) in the articular cartilage (p<0.01) and reduced chondrocyte number and loss of cartilage extracellular matrix. Both exogenous and endogenous n-3 PUFAs downregulated mTORC1 activity and promoted autophagy in articular chondrocytes. Conversely, mTORC1 pathway activation suppressed autophagy in articular chondrocytes. CONCLUSIONS: Enhancement of the synthesis of endogenous n-3 PUFAs from n-6 PUFAs can delay the incidence of OA, probably through inhibition of mTORC1, promotion of autophagy and cell survival in cartilage chondrocytes. Future investigation into the role of the endogenous n-6/n-3 PUFAs composition in OA prevention and treatment is warranted.

The necessity of indwelling gastrointestinal decompression after gastrectomy: a meta-analysis.

BACKGROUND: This meta-analysis was designed to evaluate the necessity of indwelling gastrointestinal decompression after gastrectomy. METHODS: Medline, Embase, and the Cochrane Library were searched. We identified randomized controlled trials that compared individuals with or without gastrointestinal decompression after gastrectomy, and a meta-analysis was performed on data regarding the recovery time of gastrointestinal function, length of hospital stay, complications, and mortality using fixed effect and random effect models. RESULTS: Eight randomized controlled trials that had enrolled 975 patients were included in the present study. The difference in the interval to oral intake (weighted mean difference 0.56, 95% confidence interval [CI] 0.16-0.96, P = 0.006) between the decompression group and nondecompression group was significant, but no significant differences were found in the interval to flatus (weighted mean difference 0.24, 95% CI -0.13 to 0.61, P = 0.20) or length of hospital stay (weighted mean difference 1.04, 95% CI -0.05 to 2.14, P = 0.06). Additionally, no significant differences were found in complications, including nausea or vomiting (odds ratio [OR] 1.23, 95% CI 0.57-2.65, P = 0.59), fever (OR 1.55, 95% CI 0.96-2.51, P = 0.07), pulmonary complications (OR 1.41, 95% CI 0.82-2.43, P = 0.22), anastomotic leakage (OR 1.15, 95% CI 0.55-2.40, P = 0.70), paralytic ileus or small bowel obstruction (OR 1.80, 95% CI 0.57-5.70, P = 0.32), intra-abdominal abscess (OR 1.08, 95% CI 0.50-2.34, P = 0.84), wound infection (OR 1.29, 95% CI 0.56-2.96, P = 0.55), or wound dehiscence (OR 1.47, 95% CI 0.43-4.95, P = 0.54) between the two groups. A sensitivity analysis of the pooled data from high-quality studies and studies with >20 cases per group showed that the length of hospital stay was prolonged significantly in the decompression group compared with the nondecompression group. CONCLUSIONS: Routine gastrointestinal decompression after gastrectomy does not promote the recovery of gastrointestinal function or reduce the incidence of postoperative complications. In our series, decompression was correlated with a prolonged interval to oral intake, a longer duration of hospitalization, and increased patient discomfort.

Establishing a disc degeneration model using computed tomography-guided percutaneous puncture technique in the rabbit.

BACKGROUND: Various animal models have been developed to investigate the complex mechanisms leading to intervertebral disc disorders and to evaluate the different therapeutic options. The needle puncture technique is commonly used to induce intervertebral degeneration in animal models. The present study aimed to establish a rabbit model of intervertebral disc degeneration using a simple, minimally invasive procedure. METHODS AND MATERIALS: The animal model was created in the rabbit using computed tomography-guided percutaneous puncture technology. An 18-gauge needle was used to induce a disc injury with a 5-mm puncture depth. Radiographic, histologic, and biochemical analyses and magnetic resonance imaging were performed to assess the consequent disc degeneration. RESULTS: Significant disc space narrowing was observed as early as 4 wk, and osteophytes were formed at 12 wk after puncture. The magnetic resonance imaging assessment demonstrated a progressive loss of T2-weighted signal intensity at the stabbed discs throughout the 12-wk period. The histologic analysis showed a progressive loss of the normal architecture from 4 wk to the end point. The biochemical assays suggested that the expression of proteoglycan decreased progressively with increasing time. CONCLUSIONS: A simple, but minimally invasive, intervertebral disc degeneration model was established successfully using computed tomography-guided percutaneous puncture technology in the rabbit. The puncture procedure can be performed with minimal damage and handling of the other structures, ensuring a uniform reproducible disc degeneration model.

Medial versus lateral approach in laparoscopic colorectal resection: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to investigate the safety and efficacy of the medial approach (MA) and the lateral approach (LA) in the treatment of colorectal disease. METHODS: Studies published since 1994 that compared MA versus LA in laparoscopic colorectal resection were collected. Data on conversion rate, operative time, blood loss, number of harvested lymph nodes, hospital stay, complications, mortality, rate of recurrence, and hospitalization costs for MA and LA were meta-analyzed using fixed-effect and random-effect models. RESULTS: Five cohort studies (2 randomized controlled trials and 3 retrospective studies) that included 881 patients were studied. Of these patients, 475 and 582 had undergone laparoscopic colorectal resection via MA and LA, respectively. There were significant reductions in conversion rate and operative time and possible reductions in blood loss and hospitalization costs for MA compared to LA; however, there were fewer harvested lymph nodes for MA compared with LA, which remains to be further studied. Other outcome variables such as postoperative complications, postoperative immune function, mortality, and rate of recurrence were not found to be statistically significant for either group. Sensitivity analysis on the pooled data from randomized controlled trials showed that the conversion rates were not significantly different between MA and LA. CONCLUSIONS: Compared with the lateral approach, the medial approach has the advantages of shorter operative time and possibly lower conversion rate; it also can be as safe as the lateral approach. Whether the MA has less blood loss and lower hospitalization costs remains to be confirmed, and its oncological safety and long-term prognosis are not clear. Due to insufficient data from a limited number of studies, inadequate assessment of the results may arise.

[Preliminary study for classification of spino-pelvic sagittal alignment in adult volunteers].

OBJECTIVE: To investigate the feasibility of the classification of the spino-pelvic sagittal alignment in adluts according to lumbar lordosis (LL) and inflection point (IP). METHODS: Whole spine, standing radiographs of 223 adult volunteers were taken from July to August in 2011 .There were 111 cases(56 female and 55 male) enrolled in the study based on the inclusion criteria. The pelvic and spinal parameters, including thoracic kyphosis(TK), thoracolumbar kyphosis(TLK), LL, sacral slope(SS), pelvic tilt(PT), pelvic incidence(PI), intervertebral endplate angle, sagittal vertical axis (SVA), spino-sacral angle (SSA) and IP were measured. The spino-pelvic sagittal alignment were classified in to 3 types according to LL and IP. Type I: LL > -40°, IP located below L2 ∼ 3; Type II: -60° ≤ LL ≤ -40°, IP located in L1 ∼ 2 or T12 ∼ L1; Type III: LL < -60°, P located above T11 ∼ 12. Pearson correlation analysis was used to test the correlation between the variables. The parameters in each type were compared by oneway-ANOVA respectively,then additional multiple comparisons were performed. RESULTS: The mean value of LL was -49° ± 10°, TK was 36° ± 7°, TLK was 6° ± 7°, PT was 11° ± 7°, SS was 34° ± 8°, PI was 45° ± 9°, SSA was 127° ± 9° and SVA was (-2.7 ± 22.8)mm, respectively. Only LL had significant statistical correlation with all the other parameters. Negative correlation presented between LL and TK, PI, SS, SSA (r = -0.387, -0.536, -0.858, -0.801,P < 0.05). Positive correlation presented between LL and TLK, SVA, PT (r = 0.319, 0.296, 0.262, P < 0.05). All the volunteers were classified into the 3 types: Type I1 9 cases, Type II 75 cases,Type III 17 cases. Oneway-ANOVA results showed statistical difference in LL, TK, TLK, PT, SS, PI, SSA, SVA among the 3 types, (F = 164.559, 7.431, 14.099, 4.217, 53.856, 6.252, 35.995, 8.626, P < 0.05 ). Multiple comparisons showed that LL, SS, SSA, PI had statistical difference between each two types comparison (P < 0.05). CONCLUSIONS: LL is the central parameter of the spino-pelvic sagittal balance. The patterns of the spino-pelvic sagittal alignment in adults could be classified into three types, according to LL and IP. The classification could describe the morphological differences and balance of the spino-pelvic sagittal alignment.

[Expression and significance of Slug, E-cadherin and N-cadherin in gastrointestinal stromal tumors].

OBJECTIVE: To explore the expression and clinical significance of Slug, E-cadherin and N-cadherin in gastrointestinal stromal tumors (GIST). METHODS: Seventy eight GIST specimens removed surgically from 2004 to 2007 were collected from the Department of Gastrointestinal Surgery at Guizhou Provincial People's Hospital. There were 48 males and 30 females with an age range of 28 - 87 years old. The expressions of Slug, E-cadherin and N-cadherin in GIST were determined by immunohistochemistry. And the correlations with their clinicopathologic characteristics were analyzed. RESULTS: The positive rates of Slug, E-cadherin and N-cadherin in GIST were 53.8% (42/78), 35.9% (28/78) and 75.6% (59/78) respectively. And the differences were statistically significant (χ(2) = 24.98, P < 0.05). Slug was expressed markedly higher in the cases of GIST with distant metastasis or distant metastasis and local invasion: 75% (18/24) vs 44.4% (24/54), 63.6% (28/44) vs 41.2% (14/34), both P < 0.05. And E-cadherin was expressed markedly lower in the cases of GIST with distant metastasis: 16.7% (4/24) vs 44.4% (24/54), P < 0.05. The expression of N-cadherin was not significantly different between its clinicopathological characteristics (allP > 0.05). The expression of Slug correlated negatively with that of E-cadherin (r(s) = -0.267, P = 0.018). But it had no correlation with that of N-cadherin (r(s) = 0.056, P = 0.625). CONCLUSION: Slug is expressed markedly higher while E-cadherin markedly lower in metastatic GIST, and both are closely correlated with the metastasis of GIST.

[The use of anterior cervical discectomy and fusion with self-locking cages to treat multi-segmental cervical myelopathy].

OBJECTIVE: To investigate the use of anterior cervical discectomy and fusion with self-locking cages to treat multi-segmental cervical myelopathy. METHODS: From April 2008 to March 2010, anterior cervical discectomy and fusion with self-locking cages were performed on 45 patients who suffered from multi-segmental cervical myelopathy, among of them there were 23 male and 22 female, aged from 32 to 67 years (average 53 years). Recording the Japanese Orthopedic Association (JOA) scores and SF-36 scores in the protocol time point, in order to investigate the clinical outcome, meanwhile, accumulating the pre-operation and postoperation X-ray films of cervical spine for measuring the height of intervertebral space, whole curvature of cervical spine and the rate of fusion by repeated measures analysis of variance. RESULTS: The mean follow-up time was 28.4 months (24 - 35 months). JOA scores ascended from preoperative 6.5 ± 3.1 to postoperative 13.4 ± 1.7 (F = 17.84, P = 0.001), the 7 scores of SF-36 improved significantly after operation (t = 1.151 - 12.207, P < 0.05), but mental health not. The fineness rate was 91.1%. Height of disc space ascended from preoperative (5.5 ± 1.8) mm to postoperative (8.3 ± 0.8) mm (F = 11.71, P = 0.043), globle curvature of cervical spine ascended from preoperative 5° ± 7° to postoperative 10° ± 14° (F = 234.53, P = 0.000), the change of the two index was significantly, respectively. Fat necrosis in one case and hematoma in another case at the bone donor-site were found, both of the two cases were cured by physiotherapy. All of the 45 cases (111 segments) achieved bone fusion. CONCLUSION: The use of anterior cervical discectomy and fusion with self-locking cages to treat multi-segmental cervical myelopathy possess many advantages as follows: satisfactory clinical outcome, minimally invasive, higher fusion rate, higher orthopaedic ability.

Platelet rich plasma enhanced neuro-regeneration of human dental pulp stem cells in vitro and in rat spinal cord.

Background: Human dental pulp stem cells (hDPSCs) exhibit excellent differentiation potential and are capable of differentiating into several different cellular phenotypes, including neurons. Platelet-rich plasma (PRP) contains numerous growth factors that can stimulate stem cell differentiation. In this study, we investigated the potential stimulatory effects of PRP on neurogenic differentiation and anti-apoptosis of hDPSCs in injured spinal cords. Methods: The unipotential differentiation capacity of hDPSCs was analyzed by cell surface antigen identification and cell cycle analysis. A spinal cord injury rat model composed of 40 Sprague-Dawley (SD) rats was used to facilitate an in vivo study. Rats were divided into four groups: a double-treatment group (receiving both neurogenic-induced hDPSCs and PRP), two single-treatment groups (receiving neurogenic-induced hDPSCs or PRP) and a sham group (receiving normal saline). The Basso, Beattie, Bresnahan Locomotor Rating Scale was subsequently used to evaluate the motor function of the spinal cord. Cell viability and differentiation of hDPSCs in the damaged spinal cords were analyzed and apoptosis of neural cells was evaluated using the terminal uridine nucleotide end labeling (TUNEL) assay. Results: Growth pattern, cell surface marker and cell cycle analyses revealed that hDPSCs have a high degree of multi-directional differentiation potential and can be induced into neurons in vitro. In the rat spinal cord injury model, double-treatment with hDPSC/PRP or single treatment with hDPSCs or PRP significantly improved motor function compared with the sham group (P<0.05). Apoptosis of neural cells was observed to be significantly higher in the sham group compared to any of the treatment groups. Double-treatment with hDPSCs and PRP resulted in the lowest apoptotic rate among the groups analyzed. Conclusions: hDPSCs exhibit differentiation potential and are capable of transforming into neural cells both in vitro and in vivo. Significantly increased inhibition of neuronal apoptosis and improved motor function recovery of the spinal cord were observed following double-treatment with hDPSCs and PRP compared with the single-treatment groups.

Revealing the novel autophagy-related genes for ligamentum flavum hypertrophy in patients and mice model.

Background: Fibrosis is a core pathological factor of ligamentum flavum hypertrophy (LFH) resulting in degenerative lumbar spinal stenosis. Autophagy plays a vital role in multi-organ fibrosis. However, autophagy has not been reported to be involved in the pathogenesis of LFH. Methods: The LFH microarray data set GSE113212, derived from Gene Expression Omnibus, was analyzed to obtain differentially expressed genes (DEGs). Potential autophagy-related genes (ARGs) were obtained with the human autophagy regulator database. Functional analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) were conducted to elucidate the underlying biological pathways of autophagy regulating LFH. Protein-protein interaction (PPI) network analyses was used to obtain hub ARGs. Using transmission electron microscopy, quantitative RT-PCR, Western blotting, and immunohistochemistry, we identified six hub ARGs in clinical specimens and bipedal standing (BS) mouse model. Results: A total of 70 potential differentially expressed ARGs were screened, including 50 up-regulated and 20 down-regulated genes. According to GO enrichment and KEGG analyses, differentially expressed ARGs were mainly enriched in autophagy-related enrichment terms and signaling pathways related to autophagy. GSEA and GSVA results revealed the potential mechanisms by demonstrating the signaling pathways and biological processes closely related to LFH. Based on PPI network analysis, 14 hub ARGs were identified. Using transmission electron microscopy, we observed the autophagy process in LF tissues for the first time. Quantitative RT-PCR, Western blotting, and immunohistochemistry results indicated that the mRNA and protein expression levels of FN1, TGFß1, NGF, and HMOX1 significantly higher both in human and mouse with LFH, while the mRNA and protein expression levels of CAT and SIRT1 were significantly decreased. Conclusion: Based on bioinformatics analysis and further experimental validation in clinical specimens and the BS mouse model, six potential ARGs including FN1, TGFß1, NGF, HMOX1, CAT, and SIRT1 were found to participate in the fibrosis process of LFH through autophagy and play an essential role in its molecular mechanism. These potential genes may serve as specific therapeutic molecular targets in the treatment of LFH.

Cervical Alignment of Patients with Basilar Invagination: A Radiological Study.

OBJECTIVE: To investigate the cervical alignment and the relative range of motion (ROM) in patients with basilar invagination (BI). METHODS: A total of 40 BI cases (38.1 years old ± 17.9 years old, 19 male and 21 female) and 80 asymptomatic individuals (33.8 years old ± 10.8 years old, 40 male and 40 female) were included. The Skull-C2 /Skull-BV, Skull-C7 , C2 -C7 /BV-C7 wall angles, C0 -C2 /C0 -BV, C0 -C7 , C1 -C7 , and C2 -C7 /BV-C7 angles were measured in dynamic X-ray images (including neutral, extension, and flexion positions). Correlation between the upper and lower cervical curvatures were analyzed. The total, extension, and flexion ROMs of these angles were calculated, respectively. RESULTS: The BI patients had a smaller C0 -C2 /C0 -BV angle (18.2° ± 16.4° vs 30.9° ± 9.3°), but larger C2 -C7 /BV-C7 (32.2° ± 16.1° vs 19.4° ± 10.6°) and C2 -C7 /BV-C7 wall angles (37.8° ± 17.2° vs 23.6° ± 10.2°) than the control group in neutral position. The upper and lower curvatures correlated negatively in neutral (r = -0.371), extension (r = -0.429), and flexion (r = -0.648) positions among BI patients, as well as in extension position (r = -0.317) among control group. The BI patients presented smaller total ROMs in Skull-C2 /Skull-BV (12.3° ± 16.6° vs 19.7° ± 10.9°), C0 -C2 /C0 -BV (8.1° ± 11.1° vs 17.6° ± 10.5°), and C0 -C7 angles (57.8° ± 14.2° vs 78.3° ± 17.9°), but a larger total ROM in C2 -C7 /BV-C7 wall angle (52.8° ± 13.9° vs 27.0° ± 16.1°) than the control group. The BI patients also presented smaller extension ROMs in Skull-C2 /Skull-BV (6.9° ± 9.4° vs 12.5° ± 9.3°), Skull-C7 (24.5° ± 10.9° vs 30.7° ± 12.5°), and C0 -C2 /C0 -BV angles (4.4° ± 7.8° vs 9.9° ± 8.6°) than the control group. Moreover, the BI patients showed smaller absolute values of flexion ROMs in Skull-C2 /Skull-BV (-5.2° ± 9.4° vs -7.3° ± 8.0°), C0 -C2 /C0 -BV (-3.2° ± 8.8° vs -7.7° ± 8.7°), and C0 -C7 angles (-33.2° ± 13.0° vs -52.8° ± 19.2°), but a larger absolute value of flexion ROM in C2 -C7 /BV-C7 wall angle (-33.9° ± 14.8° vs -8.2° ± 15.1°). CONCLUSION: The cervical spine was stiffer in BI patients than the asymptomatic individuals, especially in the upper cervical curvature. The negative correlation between upper and lower cervical curvatures was more obvious in BI patients.

Metformin stimulates osteoprotegerin and reduces RANKL expression in osteoblasts and ovariectomized rats.

Anti-diabetic drug metformin has been shown to enhance osteoblasts differentiation and inhibit osteoclast differentiation in vitro and prevent bone loss in ovariectomized (OVX) rats. But the mechanisms through which metformin regulates osteoclastogensis are not known. Osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) are cytokines predominantly secreted by osteoblasts and play critical roles in the differentiation and function of osteoclasts. In this study, we demonstrated that metformin dose-dependently stimulated OPG and reduced RANKL mRNA and protein expression in mouse calvarial osteoblasts and osteoblastic cell line MC3T3-E1. Inhibition of AMP-activated protein kinase (AMPK) and CaM kinase kinase (CaMKK), two targets of metformin, suppressed endogenous and metformin-induced OPG secretion in osteoblasts. Moreover, supernatant of osteoblasts treated with metformin reduced formation of tartrate resistant acid phosphatase (TRAP)-positive multi-nucleated cells in Raw264.7 cells. Most importantly, metformin significantly increased total body bone mineral density, prevented bone loss and decreased TRAP-positive cells in OVX rats proximal tibiae, accompanied with an increase of OPG and decrease of RANKL expression. These in vivo and in vitro studies suggest that metformin reduces RANKL and stimulates OPG expression in osteoblasts, further inhibits osteoclast differentiation and prevents bone loss in OVX rats.

[The application of cervical arthroplasty with Mobi-C for treatment of cervical spondylotic radiculopathy].

OBJECTIVE: To investigate the clinical effectiveness of cervical arthroplasty with Mobi-C prosthesis for treatment of cervical spondylotic radiculopathy. METHODS: From March 2008 to November 2009, a group of 67 patients with cervical spondylotic radiculopathy were analyzed retrospectively. The short form-36 physical component summary (SF-36) and visual analogue scale (VAS) score were used to compare clinical outcome pre- and postoperatively. The follow-up was performed at 3 d, 3 months, 6 months and 1 year postoperatively. Static and dynamic radiography were taken to evaluate height of disc space, range of motion (ROM) and heterotopic ossification (HO) of index levels. RESULTS: Fifty-one cases were followed up, 16 cases were lost. Average follow-up was for 19.7 months (13 - 31 months). All of patients had improvement for clinical symptoms. There was a significant difference on SF-36 between pre- and postoperatively. The significant difference was found in VAS score in which neck pain was decreased from preoperative 4.6 ± 0.4 to postoperative 2.0 ± 0.5 (P < 0.05), arm pain was decreased from preoperative 6.5 ± 0.4 to postoperative 1.3 ± 0.4 (P < 0.05). There was a significant difference in height of disc space which was increased from preoperative (6.5 ± 1.1) mm to (7.7 ± 0.9) mm (P < 0.05). ROM was increased from preoperative 7.2° ± 3.1° to latest follow-up 8.1° ± 3.2°, however, no significant difference was found concerning ROM pre- and postoperatively (P > 0.05). No other complications were met during follow-up period other than the 17 cases of heterotopic ossification in ClassI, the 7 cases in Class II in 1 year postoperatively, but no any correlation were found between the radiographic finding in HO and clinical symptoms. CONCLUSIONS: Cervical arthroplasty with Mobi-C could improve neurofunctional symptoms, maintain ROM of index level and height of disc space. For accurate patient selection, long term follow-up is still needed in prospective randomized study.

Characterization of a Novel Model of Lumbar Ligamentum Flavum Hypertrophy in Bipedal Standing Mice.

OBJECTIVE: To explore the main causes of hypertrophied ligamentum flavum (HLF) and the possibility of using bipedal standing mouse model to simulate the pathological changes in human HLF. METHODS: Thirty-two 8-week-old C57BL/6 male mice were randomly assigned to the experimental group (n = 16) and control group (n = 16). In the experimental group, mice were induced to adopt a bipedal standing posture by their hydrophobia. The experimental mice were maintained bipedal standing for 8 h a day with an interval of 2 h to consume food and water. The control mice were placed in a similar environment without bipedal standing. Eight 18-month-old C57BL/6 male mice were compared to evaluate the LF degeneration due to aging factor. Three-dimensional (3D) reconstruction and finite element models were carried out to analyze the stress and strain distribution of the mouse LF in sprawling and bipedal standing postures. Hematoxylin and Eosin (HE), Verhoeff-Van Gieson (VVG), and immunohistochemistry (IHC) staining were used to evaluate the LF degeneration of mice and humans. RT-qPCR and immunofluorescence analysis were used to evaluate the expressions of fibrosis-related factors and inflammatory cytokines of COL1A1, COL3A1, α-SMA, MMP2, IL-1ß, and COX-2. RESULTS: The von Mises stress (8.85 × 10-2 MPa) and maximum principal strain (6.64 × 10-1 ) in LF were increased 4944 and 7703 times, respectively, in bipedal standing mice. HE staining showed that the mouse LF area was greater in the bipedal standing 10-week-old group ([10.01 ± 2.93] × 104 µm2 ) than that in the control group ([3.76 ± 1.87] × 104 µm2 ) and 18-month-old aged group ([6.09 ± 2.70] × 104 µm2 ). VVG staining showed that the HLF of mice (3.23 ± 0.58) and humans (2.23 ± 0.31) had a similar loss of elastic fibers and an increase in collagen fibers. The cell density was higher during the process of HLF in mice (39.63 ± 4.81) and humans (23.25 ± 2.05). IHC staining showed that the number of α-SMA positive cells were significantly increased in HLF of mice (1.63 ± 0.74) and humans (3.50 ± 1.85). The expressions of inflammatory cytokines and fibrosis-related factors of COL1A1, COL3A1, α-SMA, MMP2, IL-1ß, and COX-2 were consistently higher in bipedal standing group than the control group. CONCLUSION: Our study suggests that 3D finite element models can help analyze the abnormal stress and strain distributions of LF in modeling mice. Mechanical stress is the main cause of hypertrophied ligamentum flavum compared to aging. The bipedal standing mice model can reflect the pathological characteristics of human HLF. The bipedal standing mice model can provide a standardized condition to elucidate the molecular mechanisms of mechanical stress-induced HLF in vivo.

[In vivo experimental study of lumbar nucleus replacement with pectin/polyvinyl alcohol composite hydrogel].

OBJECTIVE: To evaluate the anti degenerative effect of pectin/polyvinyl alcohol composite (CoPP) hydrogel as artificial nucleus material in an animal model. METHODS: Thirty-six New Zealand white rabbits were used to build animal models, the L4₋5 intervertebral discs were pierced with a Gauge#16 needle and polyvinyl alcohol (PVA) or CoPP implants were inserted into the holes. For comparative purposes, L3₋4 discs underwent sham treatment or control treatment in which the disc was pierced but no implant was inserted. All the discs were divided into four groups as follows: sham disc group, pierced disc group, PVA disc group and CoPP disc group. The discs were analyzed radiologically and histologically for degenerative changes at 1, 3 or 6 months after surgery. RESULTS: None of the animals died from operative complications, such as paraplegia or infection before being killed. Macroscopically, none of the implants showed any signs of displacement at the time of harvest. The radiological analysis revealed that significantly less disc height loss was found with the PVA and CoPP replacement treatment than with the pierced treatment (P < 0.05). Changes in disc height after the replacement treatment were not significantly different from that after the sham treatment (P > 0.05). Histological degeneration of the replaced discs was delayed in comparison with that of the pierced discs (P < 0.05), but progressed with time, and PVA replacement showed faster disc degeneration than CoPP replacement. CONCLUSIONS: Degeneration of the anulus fibrosus after the CoPP prosthetic nucleus replacement treatment is delayed by preserving disc height and occupying the space of the nucleus pulposus, and it has great potential clinical application value.

EDIL3 regulates gastric cancer cell migration, invasion and epithelial-mesenchymal transition via TGF-ß1/XIST/miR-137 feedback loop.

BACKGROUND: Human gastric cancer is a serious disease with high mortality rate all over the world. The one of difficulties in effective therapy of gastric cancer is metastasis. It has been reported that lncRNAs and miRNAs are involved in cancer metastasis. So, exploration of new molecular mechanism underlying gastric cancer metastasis involving in network of lncRNAs/miRNAs/effector proteins is important and meaningful for guiding the treatment of gastric cancer. METHODS: MTT assay, flow cytometric analysis and colony formation assay were performed to evaluate AGS or MKN-45 cell proliferation, cycle distribution and colony formation, and RT-qPCR was used to examine the expressive abundances of EDIL3, XIST and miR-137. EDIL3 and epithelial-mesenchymal transition (EMT) related proteins were detected by western blot and migration and invasion were measured by transwell analysis. Meanwhile, Dual-luciferase reporter gene assay was used to confirm XIST binding to miR-137, and miR-137 binding to EDIL3. AGS cells were used to establish the xenograft tumor model to verify the role of EDIL3 in tumorigenesis in nude mice. RESULTS: Expression levels of EDIL3 was increased in gastric cancer tissues and cell lines. Downregulation of EDIL3 or XIST and overexpression of miR-137 inhibited proliferation, migration, invasion and EMT in AGS and MKN-45 cells. XIST could specifically bind to miR-137, and EDIL3 was a target gene of miR-137. Moreover, TGF-ß1 stimulated XIST expression, inhibited miR-137 expression and induced migration, invasion and EMT. We also found that overexpression of EDIL3 elevated levels of TGF-ß1 and induced migration, invasion and EMT, which were reversed by TGF-ß1 inhibition. EDIL3 knockdown suppressed migration, invasion and EMT, which were reversed by XIST. Overexpression of miR-137 inhibited proliferation, migration, invasion and EMT, which were reversed by EDIL3 overexpression. CONCLUSIONS: EDIL3 regulates gastric cancer cell migration, invasion and EMT, which is involved in the regulation of TGF-ß1/XIST/miR-137 feedback loop, and EDIL3 knockdown inhibits tumor growth in nude mice. These findings indicate that the EDIL3 mediated molecular feedback loop may be developed as drug targets for the gastric carcinoma treatment.

Relationship between the location of ligamentum flavum hypertrophy and its stress in finite element analysis.

OBJECTIVE: To quantitatively describe the stress of the ligamentum flavum (LF) using the finite element method and to compare the stress at different parts of the healthy LF. METHODS: Based on the high resolution computed tomography imaging data of a healthy 22-year-old man, three-dimensional nonlinear L4-5 lumbar finite element model (FEM) representing intact condition was developed. The LF, as the object of the present research, was incorporated into the spinal model in the form of solid three-dimensional structure. The model's validity is verified by comparing its biomechanical indices, such as range of motion and axial compression pressure displacement, with published results under specific loading conditions. To authenticate the accuracy of the solid LF, the lamina attachments, the central cross-section, and other anatomy indicators were compared with figures in the published literature. After the average and maximum von Mises stress on the surface of LF under various working conditions were measured using ANSYS and AutoCAD software, the surface stress difference in the LF between the ventral and dorsal sides as well as the lateral and lamina parts were determined. RESULTS: The FEM predicted a similar tendency for biomechanical indices as shown in previous studies. The lamina attachments, the central cross-section, and the height as well as the width of the LF in the healthy FEM were in accordance with published results. In the healthy model, the average and maximum von Mises stress in the shallow layer of the LF were, respectively, 1.40, 2.28, 1.76, 1.48, 1.38 and 1.79, 2.41, 1.46, 1.42, 1.71 times that in the deep layer under a compressive preload of 500 N incorporated with flexion, extension, and lateral and rotational moments (10 Nm). The most conspicuous difference in surface stress was observed with the flexion motion, with a nearly 241% difference in the maximum stress and a 228% difference in the average stress compared to those in other states. As far as the whole dorsal side of the LF was concerned, the maximum surface stress was almost all concentrated in the dorsal neighboring facet joint portion. In addition, the maximum and average stress were, respectively, 77%, 72%, 15%, 11%, 71% and 153%, 39%, 54%, 200%, 212% higher in the lateral part than in the lamina part. CONCLUSION: Based on the predisposition of LF hypertrophy in the human spine and the stress distribution of this study, the positive correlation between LF hypertrophy and its stress was confirmed.

[The repair of acute spinal cord injury in rats by olfactory ensheathing cells graft modified by glia cell line-derived neurotrophic factor gene in combination with the injection of monoclonal antibody IN-1].

OBJECTIVE: To research the repair effect of transplantation of glial cell line-derived neurotrophic factor (GDNF) modified olfactory ensheathing cells (OECs) combination with injecting axonal growth inhibiting protein antibody (IN-1) in vivo. METHODS: To construct lentivirus vector with GDNF gene and infect OECs in vitro, use the immunoblotting (Western Blot) to observe the expression of GDNF was detected through Western Blot. Fifty adult female SD rats which to establish thoracic spinal cord transection injury model were randomly divided into A (control group), B (IN-1 antibody group), C (OECs group), D (GDNF-OECs group), and E (GDNF-OECs+IN-1 group) 5 groups of each 10 rats. To observe regeneration of the impaired nerve axon by NF200 immunohistochemistry, Biotinylated dextran amine (BDA) anterograde tracing corticospinal tract. Basso, Beattie and Bresnahan (BBB) score was used to evaluating hindlimb motor function recovery. RESULTS: Add up to 13 rats died post operation. OECs labeled by hoechst still survived and migrated in spinal cord 8 weeks post operation. Lots of confused and disorderly regenerated axons which crossing the injured region of spinal cord were displayed between spinal cord stumps in GDNF-OECs+IN-1 group and GDNF-OECs group; some of axons existed in OECs group, but there is no obviously continue nerve fibers crossing the injured region of spinal cord;in contrast to IN-1 and control groups, few of regenerated axons and atrophy of spinal cord stumps were observed. The results of BBB hindlimb motor rating scale were 7.70+/-0.24, 7.89+/-0.15, 10.50+/-0.25, 11.43+/-0.23 and 12.81+/-0.40 for the control group, IN-1 group, OECs group, GDNF-OECs group and the allied treatment group respectively. CONCLUSIONS: The transplantation of GDNF-OECs combination with IN-1 antibody may benefit the survival and regeneration of the injured axons, and accelerate the repair of the injured spinal cord and functional recover of hindlimb locomotor in rats in a more efficient way than that with OECs or IN-1 alone.