Physiological and transcriptome analysis of changes in endogenous hormone and sugar content during the formation of tender asparagus stems.

Asparagus is a nutritionally dense stem vegetable whose growth and development are correlated with its quality and yield. To investigate the dynamic changes and underlying mechanisms during the elongation and growth process of asparagus stems, we documented the growth pattern of asparagus and selected stem segments from four consecutive elongation stages using physiological and transcriptome analyses. Notably, the growth rate of asparagus accelerated at a length of 25 cm. A significant decrease in the concentration of sucrose, fructose, glucose, and additional sugars was observed in the elongation region of tender stems. Conversely, the levels of auxin and gibberellins(GAs) were elevated along with increased activity of enzymes involved in sucrose degradation. A significant positive correlation existed between auxin, GAs, and enzymes involved in sucrose degradation. The ABA content gradually increased with stem elongation. The tissue section showed that cell elongation is an inherent manifestation of stem elongation. The differential genes screened by transcriptome analysis were enriched in pathways such as starch and sucrose metabolism, phytohormone synthesis metabolism, and signal transduction. The expression levels of genes such as ARF, GA20ox, NCED, PIF4, and otherswere upregulated during stem elongation, while DAO, GA2ox, and other genes were downregulated. The gene expression level was consistent with changes in hormone content and influenced the cell length elongation. Additionally, the expression results of RT-qPCR were consistent with RNA-seq. The observed variations in gene expression levels, endogenous hormones and sugar changes during the elongation and growth of asparagus tender stems offer valuable insights for future investigations into the molecular mechanisms of asparagus stem growth and development and provide a theoretical foundation for cultivation and production practices.

Degradation of thiocyanate by Fe/Cu/C microelectrolysis: Role of pre-magnetization and enhancement mechanism.

Thiocyanate (SCN-), a non-volatile inorganic pollutant, is commonly found in various types of industrial wastewater, which is resistant to hydrolysis and has the potential to be toxic to organisms. Premagnetized iron-copper-carbon ternary micro-electrolytic filler (pre-Fe/Cu/C) was prepared to degrade SCN-. Pre-Fe/Cu/C exhibited the most significant enhancement effect on SCN- removal when magnetized for 5 min with an intensity of 100 mT, and the SCN- removal rate was the highest at an initial pH of 3.0 and an aeration rate of 1.6 L/min. The electrochemical corrosion and electron transfer in the pre-Fe/Cu/C system were confirmed through SEM, XPS, FTIR, XRD, and electrochemical tests. This resulted in the formation of more corrosion products and multiple cycles of Fe2+/Fe3+ and Cu0/Cu+/Cu2+. Additionally, density functional theory (DFT) calculations and electron paramagnetic resonance (EPR) were utilized to illustrate the oxygen adsorption properties of the materials and the participation of reactive oxygen species (1O2, ·O2-, and ·OH) in SCN- removal. The degradation products of SCN- were identified as SO42-, HCO3-, NH4+, and N2. This study introduced the use of permanent magnets for the first time to enhance Fe/Cu/C ternary micro-electrolytic fillers, offering a cost-effective, versatile, and stable approach that effectively effectively enhanced the degradation of SCN-.

Biomimetic Charge-Neutral Anion Receptors for Reversible Binding and Release of Highly Hydrated Phosphate in Water.

Control of phosphate capture and release is vital in environmental, biological, and pharmaceutical contexts. However, the binding of trivalent phosphate (PO4 3-) in water is exceptionally difficult due to its high hydration energy. Based on the anion coordination chemistry of phosphate, in this study, four charge-neutral tripodal hexaurea receptors (L1-L4), which were equipped with morpholine and polyethylene glycol terminal groups to enhance their solubility in water, were synthesized to enable the pH-triggered phosphate binding and release in aqueous solutions. Encouragingly, the receptors were found to bind PO4 3- anion in a 1 : 1 ratio via hydrogen bonds in 100 % water solutions, with L1 exhibiting the highest binding constant (1.2×103 M-1). These represent the first neutral anion ligands to bind phosphate in 100 % water and demonstrate the potential for phosphate capture and release in water through pH-triggered mechanisms, mimicking native phosphate binding proteins. Furthermore, L1 can also bind multiple bioavailable phosphate species, which may serve as model systems for probing and modulating phosphate homeostasis in biological and biomedical researches.

Pan-Cancer analysis of TERT and Validation in Osteosarcoma Cell Lines.

PURPOSE: To investigate the possible functions of TERT in pan-cancer and OS. METHODS: First, differential TERT gene expression analysis was conducted using multi-omics data integrative analyses, including differential expression, prognosis, the correlation between infiltrating inflammatory immune cells, and mutation in pan-cancer. Furthermore, differential TERT gene expression analysis was conducted using mRNA expression profiles related to OS based on the GEO Datasets. Various differentially expressed genes were chosen based on a fitness threshold for further investigations. Finally, the function of the TERT gene was assessed in OS cells, including cellular proliferation, migration, and metastasis. RESULTS: Pan-cancer research demonstrated that variable expression of TERT was not only associated with numerous types of human cancer but was also intimately linked to DNA methylation. Bioinformatic investigation revealed a link between the differential expression of TERT with immune cell infiltration in the tumor microenvironment (TME). In vitro studies indicated that inhibition of TERT decreased OS cell proliferation, motility, and metastasis. CONCLUSION: TERT may serve as a useful genomic biomarker for the diagnosis and prediction of pan-cancer and as a prospective therapeutic target for the treatment of OS.

Identification and verification of a BMPs-related gene signature for osteosarcoma prognosis prediction.

BACKGROUND: This study aimed to get a deeper insight into new osteosarcoma (OS) signature based on bone morphogenetic proteins (BMPs)-related genes and to confirm the prognostic pattern to speculate on the overall survival among OS patients. METHODS: Firstly, pathway analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were managed to search for possible prognostic mechanisms attached to the OS-specific differentially expressed BMPs-related genes (DEBRGs). Secondly, univariate and multivariate Cox analysis was executed to filter the prognostic DEBRGs and establish the polygenic model for risk prediction in OS patients with the least absolute shrinkage and selection operator (LASSO) regression analysis. The receiver operating characteristic (ROC) curve weighed the model's accuracy. Thirdly, the GEO database (GSE21257) was operated for independent validation. The nomogram was initiated using multivariable Cox regression. Immune infiltration of the OS sample was calculated. Finally, the three discovered hallmark genes' mRNA and protein expressions were verified. RESULTS: A total of 46 DEBRGs were found in the OS and control samples, and three prognostic DEBRGs (DLX2, TERT, and EVX1) were screened under the LASSO regression analyses. Multivariate and univariate Cox regression analysis were devised to forge the OS risk model. Both the TARGET training and validation sets indicated that the prognostic biomarker-based risk score model performed well based on ROC curves. In high- and low-risk groups, immune cells, including memory B, activated mast, resting mast, plasma, and activated memory CD4 + T cells, and the immune, stromal, and ESTIMATE scores showed significant differences. The nomogram that predicts survival was established with good performance according to clinical features of OS patients and risk scores. Finally, the expression of three crucial BMP-related genes in OS cell lines was investigated using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). CONCLUSION: The new BMP-related prognostic signature linked to OS can be a new tool to identify biomarkers to detect the disease early and a potential candidate to better treat OS in the future.

A Joint Transcriptomic and Metabolomic Analysis Reveals the Regulation of Shading on Lignin Biosynthesis in Asparagus.

Asparagus belongs to the Liliaceae family and has important economic and pharmacological value. Lignin plays a crucial role in cell wall structural integrity, stem strength, water transport, mechanical support and plant resistance to pathogens. In this study, various biological methods were used to study the mechanism of shading on the asparagus lignin accumulation pathway. The physiological results showed that shading significantly reduced stem diameter and cell wall lignin content. Microstructure observation showed that shading reduced the number of vascular bundles and xylem area, resulting in decreased lignin content, and thus reducing the lignification of asparagus. Cinnamic acid, caffeic acid, ferulic acid and sinapyl alcohol are crucial intermediate metabolites in the process of lignin synthesis. Metabolomic profiling showed that shading significantly reduced the contents of cinnamic acid, caffeic acid, ferulic acid and sinapyl alcohol. Transcriptome profiling identified 37 differentially expressed genes related to lignin, including PAL, C4H, 4CL, CAD, CCR, POD, CCoAOMT, and F5H related enzyme activity regulation genes. The expression levels of POD, CCoAOMT, and CCR genes were significantly decreased under shading treatment, while the expression levels of CAD and F5H genes exhibited no significant difference with increased shading. The downregulation of POD, CCoAOMT genes and the decrease in CCR gene expression levels inhibited the activities of the corresponding enzymes under shading treatment, resulting in decreased downstream content of caffeic acid, ferulic acid, sinaperol, chlorogenic acid and coniferin. A significant decrease in upstream cinnamic acid content was observed with shading, which also led to decreased downstream metabolites and reduced asparagus lignin content. In this study, transcriptomic and metabolomic analysis revealed the key regulatory genes and metabolites of asparagus lignin under shading treatment. This study provides a reference for further understanding the mechanism of lignin biosynthesis and the interaction of related genes.

GYY4137 protected the integrity of the blood-brain barrier via activation of the Nrf2/ARE pathway in mice with sepsis.

Injury to the blood-brain barrier (BBB) plays a vital role in sepsis-associated encephalopathy (SAE), which is one of the most common complications of sepsis. GYY4137, a new synthetic compound of hydrogen sulfide (H2 S), has extensive biological benefits. In this study, we focused on the protective effects of GYY4137 on the BBB in septic mice and the underlying mechanisms. The results suggested that whether administrated at the same time or 3 hours after LPS injection, GYY4137 both significantly alleviated the clinical symptoms and the long-term prognosis. Besides, GYY4137 improved the pathological abnormalities of septic mice. Moreover, the degradation of tight junctions in the BBB was considerably inhibited by GYY4137. In addition, GYY4137 significantly attenuated inflammation and apoptosis in the brain. Furthermore, GYY4137 activated the Nrf2/ARE pathway through the sulfhydrylation of Keap1 and inhibited oxidative stress. ML385, the specific inhibitor of Nrf2, significantly reversed the protective effects of GYY4137 in sepsis mice. In conclusion, this study indicated that through the sulfhydrylation of Keap1, GYY4137 activated the Nrf2/ARE pathway and exerted anti-inflammatory, anti-apoptotic and antioxidant effects in septic mice that consequently protected the integrity of the BBB and improved the clinical outcome of sepsis. Our findings suggest that GYY4137 might be a promising agent for the treatment of SAE.

The biological function and clinical significance of STIL in osteosarcoma.

BACKGROUND: SCL/TAL1 interrupting locus (STIL) is associated with the progression of several tumors; however, the biological role of STIL in osteosarcoma remains poorly understood. METHODS: In this study, the clinical significance of STIL in osteosarcoma was analyzed by gene chip data recorded in public databases. STIL expression was silenced in osteosarcoma cell lines to observe the effects on proliferation, apoptosis, invasion, and migration. Differentially expressed genes (DEGs) in the osteosarcoma chip were analyzed using The Limma package, and STIL co-expressed genes were obtained via the Pearson correlation coefficient. The potential molecular mechanism of STIL in osteosarcoma was further explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. RESULTS: Osteosarcoma was associated with higher STIL expression compared to the control samples, and the standardized mean difference (SMD) was 1.52. STIL also had a good ability to distinguish osteosarcoma from non-osteosarcoma samples [area under the curve (AUC) = 0.96]. After silencing STIL, osteosarcoma cell proliferation decreased, apoptosis increased, and the migratory and invasion ability decreased. A total of 294 STIL differentially co-expressed genes were screened, and a bioinformatics analysis found that differentially co-expressed genes were primarily enriched in the cell signaling pathways. The protein-protein interaction (PPI) network indicated that the hub differentially co-expressed genes of STIL were CDK1, CCNB2, CDC20, CCNA2, BUB1, and AURKB. CONCLUSIONS: STIL is associated with osteosarcoma proliferation and invasion, and may be promote the progression of osteosarcoma by regulating the expression of CDK1, CCNB2, CDC20, CCNA2, BUB1 and AURKB.

The protective effect of polyethylene glycol-conjugated urokinase nanogels in rat models of ischemic stroke when administrated outside the usual time window.

pH-sensitive polyethylene glycol-conjugated urokinase nanogels (PEG-UK) is a new form of urokinase (UK) nanogels that could release UK at certain pH values. In our former study, we demonstrated that the pH value in the infarcted brain significantly declined to the level that could trigger the delivery of UK from PEG-UK. Thrombolysis is recommended as the first choice for ischemic stroke within the time window. However, it is common for the patients to miss the thrombolysis time window, which is one of the major causes of bad prognosis from ischemic stroke. It remains promising for seeking therapeutic approaches for ischemic stroke by investigating potential protective reagents delivered out of the usually thrombolysis time window. In this study, the protective effect of administration of PEG-UK outside the usual time window and the underlying mechanisms were investigated. PEG-UK was administrated 2 h and a half after ischemic stroke Delayed administration of PEG-UK significantly ameliorated the severity of neurological deficits of permanent middle cerebral occlusion (pMCAO) rats and reduced the infiltration of inflammatory cells and the concentration of interleukin 1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the brain tissues. The content of water and the leakage of Evans Blue (EB) in the PEG-UK group were also decreased. Maintenance of the expression of platelet-derived growth factor-C (PDGF-C) and inhibition of the upregulation of metalloproteinase proteins, low-density lipoprotein receptor-related protein (LRP), nuclear factor κB (NF-κB) p65 and cyclooxygenase-2 (Cox-2) were observed through western blotting and realtime PCR in the PEG-UK group. Besides, delayed administration of PEG-UK attenuated the up regulation of Caspase8 and Caspase9 and the cleavage of Caspase3 and poly (ADP-ribose) polymerase 1 (PARP1) in ischemic lesion sites. Moreover, PEG-UK treatment also inhibited the upregulation and phosphorylation of N-methyl-D-aspartic acid receptors (NMDARs), which has been revealed to play a vital role in mediating excito-neurotoxicity in ischemic stroke. In conclusion, through the inhibition of LRP/NF-κB/Cox-2 pathway, the Caspase cascade and activation of NMDARs, administration of PEG-UK outside the usual time window could still exert protective effects in pMCAO rats through the maintenance of the integrity of BBB and the inhibition of apoptosis and excito-neurotoxicity.

Andrographolide prevents human nucleus pulposus cells against degeneration by inhibiting the NF-κB pathway.

Intervertebral disc degeneration (IDD) is among the most common spinal disorders, pathologically characterized by excessive cell apoptosis and production of proinflammatory factors. Pharmacological targeting of nucleus pulposus (NP) degeneration may hold promise in IDD therapy, but it is limited by adverse side effects and nonspecificity of drugs. In this study, we used a natural compound, andrographolide (ANDRO), which has been widely used to intervene inflammatory and apoptotic diseases in the investigation of NP degeneration based on IDD-patients-derived NP cells by lipopolysaccharide (LPS) treatment for the preservation of degeneration. The results showed that LPS maintained the degeneration status of NP cells as evidenced by a high apoptosis rate and the expression of degenerative and inflammatory mediators after LPS treatment. ANDRO reversed the effects of LPS-caused degeneration of NP cells and maintained the phenotype of NP cells, as demonstrated by flow cytometry, degenerative mediators (ADAMTS4 and ADAMTS5), inflammatory factors (COX2, PGE2, MMP-13, and MMP-3), biomarkers of NP cells (SOX9, ACAN, and COL2A1) expressions, and glycosaminoglycan secretion. We also found the involvement of the nuclear factor kappa-light-chain-enhancer of the activated B cells (NF-κB) pathway in ANDRO treatment, indicating that ANDRO prevented the LPS-preserved degeneration of NP cells by inhibiting the NF-κB pathway. This study may provide a reference for clinic medication of IDD therapy.

Clinical predictors for the prognosis of myasthenia gravis.

BACKGROUND: Clinical predictors for myasthenia gravis relapse and ocular myasthenia gravis secondary generalization during the first two years after disease onset remain incompletely identified. This study attempts to investigate the clinical predictors for the prognosis of Myasthenia Gravis. METHODS: Eighty three patients with myasthenia gravis were concluded in this study. Baseline characteristics were analyzed as predictors. RESULTS: Relapse of myasthenia gravis developed in 26 patients (34%). Generalization developed in 34 ocular myasthenia gravis patients (85%). Other autoimmune diseases were observed more commonly in relapsed myasthenia gravis (P = 0.012). Second generalization group contained more late onset patients (P = 0.021). Ocular myasthenia gravis patients with thymus hyperplasia progressed more rapidly than those with other thymus pathology (P = 0.027). Single onset symptom of ocular myasthenia gravis such as ptosis or diplopia predicted early progression than concurrence of ptosis and diplopia (P = 0.027). Treatment effect including glucocorticoid, pyridostigmine, thymectomy, IVIG, immunosuppressive drugs did not show significant difference between the relapsed and non-relapsed groups. The treatment outcome also showed no difference between the single OMG and second generalized groups. CONCLUSIONS: Occurrence of associated autoimmune disease can serve as a potential predictor for myasthenia gravis relapse. Either ptosis or diplopia, as well as thymic hyperplasia can predict generalization in the first six months.

Efficacy and safety of a novel acetylcholinesterase inhibitor octohydroaminoacridine in mild-to-moderate Alzheimer's disease: a Phase II multicenter randomised controlled trial.

Background: inhibition of acetylcholinesterase (AChE) has been a effective treatment for Alzheimer's disease (AD). Octohydroaminoacridine, a new AChE inhibitor, is a potential treatment for AD. Method: we conducted a multicenter, randomised, double blind, placebo-controlled, parallel-group Phase II clinical trial to investigate the effects of octohydroaminoacridine in patients with mild-to-moderate AD. Patients were randomised to receive placebo thrice daily, octohydroaminoacridine 1 mg/thrice daily (TID) (low-dose group), 2 mg/TID (middle-dose group) or 4 mg/TID (high-dose group). Doses in the middle-dose and high-dose group were titrated over 2-4 weeks. Changes from baseline to Week 16 were assessed with the AD Assessment Scale-Cognitive Subscale (ADAS-cog), Clinician's Interview-Based Impression of Change Plus (CIBIC+), activities of daily living (ADL) and the neuropsychiatric inventory (NPI). ADAS-cog was the primary end point of the study. A two-way analysis of covariance and least squares mean t-test were used. Results: at Week 16, the changes from baseline in ADAS-cog were 1.4, -2.1, -2.2 and -4.2 for placebo, low-, middle- and high-dose groups, respectively. Patients in the high-dose group had better performance in CIBIC+ and ADL scores at the end of the study. There was no significant difference in the change in NPI score among the groups. The effects of octohydroaminoacridine were dose dependent, and were effective within 16 weeks of treatment. No evidence was found for more adverse events that occurred in different drug groups than placebo group. Conclusions: octohydroaminoacridine significantly improved cognitive function and behaviour in patients with mild-to-moderate AD and this effect was dose dependent.

Vitamin D receptor gene polymorphisms and lumbar disc degeneration: a systematic review and meta-analysis.

PURPOSE: To examine the association between Vitamin D receptor (VDR) gene polymorphisms and lumbar disc degeneration (LDD) predisposition. METHODS: A comprehensive literature search was conducted to identify all the relevant studies. The allele/genotype frequencies were extracted from each study. We calculated the pooled odds ratios (ORs) and 95 % confidence intervals (CI) to assess the strength of the association between the VDR gene polymorphisms and LDD risk. Statistical analysis was performed using RevMan 5.31 software. RESULTS: A total of 23 case-control studies (1835 cases and 1923 controls) were included in this systematic review. For the TaqI (rs731236), FokI (rs2228570) and ApaI (rs7975232) polymorphisms of VDR gene, nine studies, seven studies, and five studies, were eventually included in the meta-analysis, respectively. There was no evidence that the VDR gene polymorphisms (TaqI, FokI, ApaI) had significant associations with LDD risk.(for TaqI allelic comparison, OR = 1.07, 95 % CI 0.81-1.40, p = 0.64; for FokI allelic comparison, OR = 1.23, 95 % CI 0.83-1.82, p = 0.31; for ApaI allelic comparison, OR = 0.79, 95 % CI 0.55-1.14, p = 0.20). For stratified analyses by ethnicity and study design, no significant associations were found in Caucasian population and Asian population, as well as the population-based studies and hospital-based studies under all genetic models. CONCLUSIONS: TaqI, FokI, and ApaI polymorphisms of VDR gene were not significantly associated with the predisposition of LDD. Large-scale and well-designed international studies are needed to further analyze this field.

ß2-Adrenergic receptor gene polymorphisms in the relapse of myasthenia gravis with thymus abnormality.

BACKGROUND: The role of ß2-adrenergic receptor (ß2-AR) in the relapse of myasthenia gravis (MG) associated with thymus abnormality has not been fully identified. METHODS: Using polymerase chain reaction and gene sequencing method, we investigated the relationship of ß2-AR gene polymorphisms with different thymus pathology in MG patients. The role of ß2-AR gene polymorphisms in the relapse of MG was further investigated. RESULTS: Age of onset (p = 0.034), the onset symptom of ocular MG (OMG; p = 0.023), the first symptom of OMG second generalization (p = 0.040) were different in MG with thymoma from those in MG with normal thymus or thymus hyperplasia. Gene polymorphisms of ß2-AR on positions 16 and 27 showed no significant difference between relapsed and non-relapsed MG patients with thymus abnormality (thymus hyperplasia: position 16, p = 0.792; position 27, p = 0.664; thymoma: position 16, p = 0.226; position 27, p = 0.615). However, genotypes distribution on position 27 among MG patients with three thymus histology was significantly different (χ² = 8.153, p = 0.041). Furthermore, glucocorticoid can decrease relapse of MG with thymus hyperplasia (p = 0.021). CONCLUSIONS: MG patients with thymus abnormality differ from MG patients with normal thymus in age of onset, the onset symptom of OMG and the first symptom of OMG second generalization. ß2-AR gene polymorphisms had no relationship with the relapse of MG with thymus abnormality. Gene polymorphism of ß2-AR on position 27 was associated with different thymus histology of MG. Glucocorticoid was able to reduce the risk of relapse of MG with thymus hyperplasia.

Association of GRM4 gene polymorphisms with susceptibility and clinicopathological characteristics of osteosarcoma in Guangxi Chinese population.

Osteosarcoma is the most frequent malignant primary bone tumor. GRM4 is expressed in human osteosarcoma cells, and high expression of mGluR4 in osteosarcoma tissues is related to poor prognosis. The aim of this study was to investigate the association between polymorphism of the GRM4 gene and the susceptibility to osteosarcoma in a Chinese population. In a case-control study, we investigated polymorphisms in the GRM4 gene (rs2229901, rs733457, and rs1906953) with a real-time quantitative polymerase chain reaction (PCR) assay (TaqMan). The study was conducted with 126 Chinese patients with osteosarcoma and 168 Chinese subjects in a control group. Unconditional logistic regression was used to analyze the correlation between single nucleotide polymorphisms (SNPs) and osteosarcoma risk. Different survival rates of different genotypic patients with osteosarcoma were analyzed through Kaplan-Meier. There were statistically significant differences in the distributions of the rs1906953 genotypes between the cases and control group (P = 0.034). However, there was no remarkable difference in the three genotypes of GRM4 gene rs2229901 locus between the patient group and control group (P = 0.369). Survival analysis for rs1906953 showed that the median survival time of osteosarcoma patients with the CC genotype was significantly shorter compared to the CT and TT genotypes; patients carrying CC genotype have apparently got a decrease in their recurrence-free survival time in comparison with patients carrying TT genotype. Our data suggest that GRM4 gene polymorphism is closely related to the morbidity and metastasis of osteosarcoma in a Chinese population.

Correlation between TGF-ß1 gene 29 T > C single nucleotide polymorphism and clinicopathological characteristics of osteosarcoma.

Transforming growth factor (TGF)-ß1 is the most abundant growth factor in human bone. Several polymorphisms have been described in the TGF-ß1 gene. To explore the correlation between TGF-ß1 gene single nucleotide polymorphism and the clinicopathological characteristics of osteosarcoma. TaqMAN PCR technique was used to detect the TGF-ß1 gene polymorphism of 124 patients with osteosarcoma from last follow-up and 136 healthy controls. The difference of gender, age, and allele frequency between patient group and control group with χ (2) text were tested. The relationship between single nucleotide polymorphism and the risk of osteosarcoma with logistic regression and different survival rates of different genotypic patients with osteosarcoma through Kaplan-Meier were analyzed. There is no remarkable difference of the three genotypes in TGF-ß1 gene 509C > T locus between the patient group and control group (P = 0.26). However, there are significant distributive differences in 29 T > C genotype (P = 0.04), which shows that patients carrying TT genotype have more risk to get osteosarcoma than patients carrying CC genotype (odds ratio (OR) = 2.10, 95 % confidence interval (CI) = 1.08-4.05). The percentage of T allele frequency of patient group, as 60.1 %, is larger than the control group, as 48.9 %. By comparing with patients carrying CC genotype, patients carrying TT genotype have two times risk of metastasis (OR = 2.30, 95 % CI = 1.05-5.06), and most of them are in the period of Enneking IIB (OR = 2.54, 95 % CI = 1.18-5.51). The survival analysis indicates that there is no any significant decrease when there is recurrence in patients carrying TT genotype. The morbidity and metastasis of osteosarcoma are relevant to TGF-ß1 gene 29 T > C single nucleotide polymorphism.

Occipito-cervical fusion following gross total resection for the treatment of spinal extramedullary tumors in craniocervical junction: a retrospective case series.

BACKGROUND: Previous studies found that the facet joint of the C1 vertebra were removed (C1 facetectomy) before extirpation from the extramedullary tumor in craniocervical junction, leading to postoperative upper cervical instability or deformity. Occipito-cervical fusion (OCF) is a demanding and morbid surgical procedure, which can be used in such patients. This study is to analyze the clinical manifestation and surgical outcome of patients with craniocervical extramedullary tumor undergoing an extirpation of spinal tumors and OCF by one-stage posterior approach. METHODS: The surgical and clinical databases were searched for operative procedures that had been performed for patients with spinal extramedullary tumors in craniocervical junction at a single institution from January 2008 to July 2011. The following inclusion criteria were applied: (1) initial surgery for craniocervical extramedullary tumor, (2) gross total resection and occipito-cervical fusion had been performed, (3) minimum 2-year follow-up, and (4) no previous cervical spine surgery. Medical records included demographic characteristics, clinical assessment, and radiographic studies. Clinical outcomes before and after the surgery were assessed using Frankel grade and the Japanese Orthopaedic Association (JOA) score. Cervical sagittal alignment was evaluated by C0-2 angle and C2-7 angle based on X-ray. RESULTS: Nine patients were included in the study. Five patients had schwannoma, three patients had meningioma, and only one patient had neurofibroma. All cases were followed up for 24-42 months (average, 34.2 months). At the last follow-up, three patients improved from Frankel grade C to grade D, two patients from Frankel grade C to grade E, and one patient from Frankel grade D to grade E, while two patients remained stationary at the Frankel grade D. The JOA score of the eight patients were 9.0 (range, 6-17) before surgery and were 14.6 (range, 12-17) at the most recent follow-up (p < 0.05). The mean C0-2 angle and the mean C2-7 angle before surgery were 26.2 ± 5.3° and 17.4 ± 13.1°, respectively. At the end of follow-up, the mean C0-2 angle was 25.6 ± 4.8°, and the mean C2-7 angle decreased to 12.7 ± 10.9°. However, this trend did not reach statistical significance (p < 0.05). Two patients suffered from cerebrospinal fluid leaks postoperatively. All patients had a satisfactory fusion and did not exhibit a tumor recurrence during the follow-up period. CONCLUSIONS: OCF following gross total resection appears to be a useful surgical procedure for the craniocervical extramedullary tumors requiring C1 facetectomy and does not cause postoperative kyphosis of the upper cervical spine.

[Study of the association of ß2-adrenergic receptor gene polymorphism with Myasthenia Gravis associated with thymus abnormality].

OBJECTIVE: To investigate the association of two ß2-adrenergic receptor (ß2-AR) polymorphisms (Arg16Gly, Gln27Glu) with Myasthenia Gravis (MG) associated with thymus abnormality. METHODS: Among the 74 MG patients in analysis, 24 cases were associated with thymoma, 40 cases with thymic hyperplasia, 12 with normal thymus. The genotypes of ß2-AR in 76 MG (MGG) and 75 age and gender-matched healthy controls (HCG) were determined by polymerase chain reaction and nucleotide sequence determination. RESULTS: The frequencies of three genotypes (Arg/Arg, Arg/Gly, Gly/Gly) and alleles (Arg, Gly) in position 16 between MGG with thymoma and HCG (genotype χ(2) = 0.460, P = 0.895; allele χ(2) = 0.137, P = 0.711), MGG with thymic hyperplasia and HCG were not statistically insignificant (genotype χ(2) = 2.585, P = 0.278;allele χ(2) = 0.300, P = 0.584). The difference in distribution of the genotypes (Gln/Gln, Gln/Glu, Glu/Glu) and alleles (Gln, Glu) between MGG with thymoma and HCG (genotype P = 0.866; allele χ(2) = 0.030, P = 0.860), MGG with thymic hyperplasia and HCG (genotype P = 0.907; allele χ(2) = 0.373, P = 0.542) were statistically insignificant. The genotypes distribution of position 27 in different thymus histology (thymoma, thymic hyperplasia, normal thymus) of MGG were significantly different (P = 0.041). The genotype frequencies in all groups were both in Hardy-Weinberg equilibrium (P > 0.05). CONCLUSION: Arg/Gly and Gln/Glu polymorphisms of ß2-AR might have no relationship with the risk of MG associated with thymus abnormality. The genotypes polymorphism of position 27 may related with the different thymus histology of MG.

Glucocorticoid receptor DNA binding factor 1 expression and osteosarcoma prognosis.

Glucocorticoid receptor DNA binding factor 1 (GRF-1) is an important Rho family GTPase-activating protein, and the dysregulation of GRF-1 expression maybe involved in tumor progression. However, the role of GRF-1 expression in the osteosarcoma prognosis has been well less elaborated. Here, we conducted a hospital-based case study, including 247 patients with pathologically confirmed osteosarcoma to evaluate the associations between GRF-1 expression and osteosarcoma prognosis. We found that high GRF-1 expression was correlated with poor outcome of osteosarcoma compared with low GRF-1 expression (the median recurrence-free survival times, 11 months vs 56 months; the median overall survival times, 18 months vs 53 months). Like tumor stage, the GRF-1 expression was an independent prognostic factor influencing the survival of osteosarcoma [hazard ratio values (95 % confidence interval) were 5.39 (3.54-8.20) for recurrence-free survival (RFS) and 6.58 (4.44-9.74) for overall survival (OS), respectively]. Furthermore, the high expression of GRF-1 was significantly associated with larger tumor size, tumor dedifferentiation, and increasing metastasis risk. Functionally, the knockdown of GRF-1 expression inhibited tumor cells proliferation and induced cell apoptosis. These results indicate for the first time that GRF-1 expression may modify osteosarcoma prognosis and may be a potential tumor therapeutic target.

COL1A1 polymorphism is associated with risks of osteosarcoma susceptibility and death.

Osteosarcoma is a life-threatening malignancy that often occurs in teenagers. Collagen type I alpha 1 (COL1A1) polymorphism is reportedly associated with the occurrence of several human diseases. However, the relationship between COL1A1 and osteosarcoma occurrence remains unknown, and there is no report about the prevalence of COL1A1 in osteosarcoma. The purpose of this study is to investigate the associations of COL1A1 polymorphism with the susceptibility and survival of osteosarcoma. The relative risk to develop osteosarcomas and the overall survival associated to COL1A1 polymorphism were investigated in a homogeneous group of 189 osteosarcomas patients. Correlations with overall survival and hazard ratios (HR) were also analyzed. CT genotype and C allele of COL1A1 at rs1061970, and CG genotype and G allele of COL1A1 at rs2075559 are associated with decreased susceptibility to osteosarcoma in the Chinese population. CC genotype and C allele of COL1A1 at rs1061970 are associated with nonmetastasis in patients. CC genotype and CT genotype of COL1A1 at rs1061970 are associated with lower risk of death. Metastasis was found to be an independent prognostic factor for survival. This study provides the first evidence for the association between COL1A1 polymorphism and osteosarcoma risk in Chinese and shows that COL1A1 polymorphism at rs1061970 has a prognostic value for overall survival in osteosarcoma patients.