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To investigate the prognostic value of metabolic syndrome (MetS) and its relationship with renal structure changes in patients with type 2 diabetes and associated diabetic nephropathy (DN).411 Chinese patients with type 2 diabetes and biopsy-confirmed DN were enrolled in this retrospective study. MetS was defined according to the modified criteria of the 2005 International Diabetes Federation. Baseline demographics and clinical information at the time of renal biopsy were extracted from the hospital's electronic medical records system. Renal pathological findings were assessed according to Renal Pathology Society system. Univariate and multivariate logistic regression analyses were performed to define the pathological covariates associated with MetS. A competing risk model, with death as the competing risk, was used to estimate the sub-distribution hazard ratio (SHR) of MetS for end-stage kidney disease (ESKD).224 (55%) patients had MetS. Patients with MetS had poor renal function and more severe interstitial fibrosis tubular atrophy scores (IFTA) than those without MetS. Multivariate logistic regression analysis revealed that IFTA was significantly associated with MetS (odds ratio per score increase 1.45, 95% confidence interval [CI] 1.02-2.05). Of the patients with DN at risk, 40% of patients progressed to ESKD. After adjusting for renal function and pathological parameters, the presence of MetS was an independent predictor for progression to ESKD (SHR 1.93, 95% CI 1.34-2.79). The SHRs for progression to ESKD also increased as the number of MetS components increased. Additionally, adding the IFTA scores improved the prognostic power of a model that only contained MetS and clinical covariates for predicting future ESKD.MetS is an independent prognostic predictor of ESKD in patients with T2D and DN, while adding the IFTA scores increased the prognostic value of MetS for renal outcome.

We aimed to confirm the association between some single nucleotide polymorphisms (SNPs) and metabolic dysfunction-associated fatty liver disease (MAFLD) in western China.A total of 286 cases and 250 healthy controls were enrolled in our study. All samples were genotyped for patatin-like phospholipase domain containing 3 (PNPLA3) rs738409, transmembrane 6 superfamily member 2 (TM6SF2) rs58542926, membrane-bound O-acyltransferase domain containing 7 (MBOAT7) rs641738, glucokinase regulator (GCKR) rs1260326 and rs780094, and GATA zinc finger domain containing 2A (GATAD2A) rs4808199. Using logistic regression analysis, we evaluated the association between MAFLD and each SNP under different models. Multiple linear regression was used to find the association between SNPs and laboratory characteristics. Multifactor dimensionality reduction was applied to test SNP-SNP interactions.The recessive model and additive model of PNPLA3 rs738409 variant were related to MAFLD (odds ratio [OR] = 1.791 and 1.377, respectively, p = 0.038 and 0.027, respectively). However, after Benjamini-Hochberg adjustment for multiple tests, all associations were no longer statistically significant. PNPLA3 rs738409 correlated with AST levels. GCKR rs780094 and rs1260326 negatively correlated with serum glucose but positively correlated with triglycerides in MAFLD. Based on MDR analysis, the best single-locus and multilocus models for MAFLD risk were rs738409 and six-locus models, respectively.In the Han population in western China, no association was found between these SNPs and the risk of MAFLD. PNPLA3 rs738409 was associated with aspartate aminotransferase levels in MAFLD patients. GCKR variants were associated with increased triglyceride levels and reduced serum fasting glucose in patients with MAFLD.

Objective: DBPR108, a novel dipeptidyl-peptidase-4 inhibitor, has shown great antihyperglycemic effect in animal models. This study was to evaluate the efficacy and safety of DBPR108 monotherapy in...

Conflicting findings have been reported concerning the survival of patients treated with limb salvage and amputation for osteosarcoma. This study aimed to identify predictors associated with surgery types and survival difference. Patients with osteosarcoma were selected from the Surveillance Epidemiology and End Results database (1975–2016). Multivariable logistic regression analysis was conducted, and a nomogram was further established. Propensity score matching (PSM)-adjusted Kaplan–Meier curves, log-rank tests, Cox proportional hazards regression analysis were performed to compare overall survival (OS) and cancer-specific survival (CSS). Among 3363 patients with osteosarcoma, 2447 and 916 underwent limb salvage and amputation. Predictors associated with amputation in the nomogram included age, gender, primary tumor site, tumor grade, tumor stage, tumor size and radiotherapy. Totally 900 pairs of patients treated with limb salvage and amputation were matched after PSM. Limb salvage was significantly associated with improved OS (HR, 0.773; 95% CI, 0.670–0.892; p

Background The triglyceride and glucose index (TyG) and triglyceride-to-high density lipoprotein cholesterol ratio (TG/HDL-C) were found to be substitute markers of insulin resistance (IR). We aimed to compare the efficacy of the two indicators in the diagnosis of Metabolic-Associated Fatty Liver Disease (MAFLD), which was rarely covered in the literature, and to construct a novel disease diagnosis model.Methods A retrospective cross-sectional study was carried out in West China Hospital of Sichuan University and 229 people (97 MAFLD and 132 Non-MAFLD) were included. Biochemical indexes were collected and analyzed by logistic regression to screen out indicators that expressed differently in MAFLD patients and healthy controls and incorporate them into a diagnostic model. MAFLD was diagnosed by Ultrasound.Results After adjusting for age, gender and BMI, Serum ALT, AST, AST/ALT (A/A), FPG, Cys-C, URIC, TG, HDL-C, ALP, GGT, nonHDL-C, LDL-C/HDL-C, nonHDL-C/HDL-C, TG/HDL-C, TC/HDL-C, TyG and TyG-BMI were risk factors of MAFLD through binary logistics regression analysis. The odds ratio of TG/HDL-C and TyG were 5.387 (95%CI: 2.986-9,718) and 107.945 (95% CI: 25.824-451.222). In identifying MAFLD, TyG, TG/HDL-C and TG were found to be the most vital indexes by the random forest method and the area under the curve (AUC) of them are all greater than 0.9 respectively. In addition, the combination of gender, BMI, ALT, TG, HDL-C, TyG and TyG-BMI had a great diagnostic efficiency for MAFLD.Conclusions TyG and TG/HDL-C were potential risk factors for MAFLD and the former made a better performance in diagnosing MAFLD. The combination of gender, BMI, ALT, TG, HDL-C, TyG and TyG-BMI improved the diagnostic capability of MAFLD.

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Background Fibroblast growth factor (FGF) and tumor growth factor-β (TGFβ) have emerged as pivotal regulators during the progression of osteosarcoma (OS). LHX9 is one crucial transcription factor controlled by FGF, however, its function in OS has not been investigated yet. Methods The expression of LHX9, FRS2, BMP4, TGF-beta R1, SMAD2, beta-catenin and metastasis-related proteins was measured by real-time quantitative PCR (RT-qPCR) and Western blot. CCK-8 assay and colony formation assay were employed to determine the proliferation of OS cells, while scratch wound healing assay and transwell assay were used to evaluate their migration and invasion, respectively. In vivo tumor growth and metastasis were determined by subcutaneous or intravenous injection of OS cells into nude mice. Results LHX9 expression was evidently up-regulated in OS tumor tissues and cell lines. Knockdown of LHX9 impaired the proliferation, migration, invasion and metastasis of OS cells. Mechanistically, LHX9 silencing led to the down-regulation of BMP-4, β-catenin and metastasis-related proteins, which was also observed in beta-catenin knockdown OS cells. By contrast, FRS2 knockdown conduced to the up-regulation of LHX9, BMP4, β-catenin and TGF-βR1, while TGF-beta inhibition repressed the expression of LHX9 and metastasis-related proteins. Additionally, let-7c modulates LHX9 and metastasis-related proteins by suppressing TGF-beta R1 expression on transcriptional level. Conclusions This study revealed LHX9 was essential for the proliferation, migration, invasion, and metastasis of OS cells via FGF and TGF-β/β-catenin signaling pathways.

Background: To explore the construction of the trainers' ability system of the community practice base of general practice under the background of hospital / community integrated teaching of general practice. Methods: literature analysis, Delphi discussion and questionnaire survey were used in the study, and exploratory factor analysis was used to extract competency. Results: there are 4 first level indicators and 20 second level indicators in the system, among which the first level indicators are: personal characteristics and professionalism, teaching and research ability, basic level clinical practice ability, and base organization management ability. Conclusion: the index system enriches the theory of teachers' ability in community practice base of general practice medicine, and provides empirical research basis for the selection, ability training and performance evaluation of teachers in community practice base of general practice medicine.

Benign optic nerve gliomas were rarely found in adults, and total resection of these lesions seems impossible. We aimed to share a rare clinical case with an unusual and instructive treatment process.A 52-year-old woman complained of a 4-month history of visual disturbance. Automated perimetry revealed visual field defect in her both eyes.This patient was diagnosed with optic nerve glioma. We found its pathological features consistent with the pilocytic astrocytomas (WHO grade I).A total resection of the tumor was smoothly performed.Repeat MRI 3 months after the surgery demonstrated no recurrence of the lesion. Two years of postoperative telephone follow-up showed a stable status of improved vision.We reported this interesting case to show a rare kind of condition regarding optic nerve gliomas in adults, which might help neurosurgeons like us to diagnose and treat these "invisible" tumors.

Lifestyle interventions and pharmacotherapy are the most common of non-invasive treatments for atherosclerosis, but the individual effect of diet on plaques remains unclear. The current study aimed to investigate the effect of withdrawing the atherogenic diet on plaque in the aortas of rabbits. Experimental atheroma was induced in 33 rabbits using a 1% high cholesterol diet for 30 days (H-30 d) or 90 days (H-90 d, baseline group). After 90 days of the atherogenic diet, the remaining animals were divided into four groups: A total of 10 rabbits continued to consume the atherogenic diet for 50 days (H-90 d & H-50 d; n=5) or 140 days (H-90 d & H-140 d; n=5). Another 13 rabbits were switched to a chow diet for 50 days (H-90 d & C-50 d; n=7) or 140 days (H-90 d & C-140 d; n=6). A total of 10 age-matched rabbits in the control groups were fed a chow diet for 90 and 230 days, respectively. The en face or cross-sectional plaque areas were determined using oil red O staining and elastic van Gieson staining. Immunohistochemistry analyses were used to assess the macrophages or smooth muscle cell contents. When fed an atherogenic diet for 90 days, the rabbits' abdominal aortas exhibited severe atherosclerotic lesions (the median en face plaque area was 63.6%). After withdrawing the atherogenic diet, the plaque area did not shrink with feeding the chow diet compared with the baseline, but increased to 71.8 or 80.5% after 50 or 140 days, respectively. After removing cholesterol from the diet, the lipids content in the plaques increased during the first 50 days, and then decreased compared with the baseline group. Furthermore, withdrawing the atherogenic diet increased the total collagen content and the percentage of the smooth muscle cells, alleviated macrophage infiltration, decreased the vulnerable index and promoted the cross-linking of collagen. Feeding the rabbits an atherogenic diet followed by removal of cholesterol from the diet did not lead to the regression of established lesions but instead delayed the progression of the lesions and promoted the stabilization of the plaque.

Background: MiR-193a-5p has been observed to have oncogenic or tumor-suppressive function in different kinds of cancers. Na+/Ca2+ exchangers (NCX1, NCX2 and NCX3) normally extrude Ca2+ from the cell, and deregulation of the intracellular Ca2+ homeostasis is related to several kinds of diseases, including cancer. However, their roles and molecular mechanism in osteosarcoma are elusive.Methods: The expression of miR-193a-5p and NCX2 in osteosarcoma and corresponding adjacent noncancerous tissues was investigated by qRT-PCR. Colony formation assay, wound healing assay, transwell invasion assay and xenograft mouse model were used for in vitro and in vivo functional analyses. Tandem mass tag-based quantitative proteomics analysis was performed to identify the targets of miR-193a-5p.Results: This study showed that miR-193a-5p was upregulated in osteosarcoma tissues compared with the corresponding adjacent noncancerous tissues, and promoted colony formation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro, as well as metastasis in vivo. Quantitative proteomics analysis identified NCX2 as a potential target of miR-193a-5p. Luciferase activity assay and Western blotting further confirmed that miR-193a-5p recognized the 3′-untranslated region of NCX2 mRNA, and negatively regulated NCX2 expression. NCX2 was downregulated in osteosarcoma tissues, and its expression was negatively correlated with miR-193a-5p levels. Ectopic expression of NCX2 in osteosarcoma cells could counteract the oncogenic effects of miR-193a-5p. These results indicate that miR-193a-5p exerts its effects by targeting NCX2. Further study demonstrated that NCX2 suppressed Ca2+-dependent Akt phosphorylation by decreasing intracellular Ca2+ efflux, then inhibited EMT process. Treatment with the antagomir against miR-193a-5p sensitized osteosarcoma to the Akt inhibitor afuresertib in a murine xenograft tumor model. Conclusion: This study revealed a miR-193a-5p/NCX2/AKT signaling axis in the progression of osteosarcoma, which may provide a new therapeutic target for osteosarcoma treatment.

Asymmetric dihydroxylation and epoxidation are well-developed and widely used approaches to introduce chiral oxygenated functional groups with an alkene substrate. However, oxohydroxylation of an alkene, furnishing adjacent oxo and hydroxy groups, is less explored. In this paper, asymmetric oxohydroxylation of α-alkyl enoates with potassium permanganate catalyzed by monocationic quaternary ammonium salts derived from cinchona alkaloid is reported. A series of α-hydroxy-β-keto esters were obtained in up to 96% yield and 98% ee under user-friendly conditions. Synthetic application of oxohydroxylation was demonstrated in the synthesis of key chiral building blocks for thapsigargin and camptothecin synthesis. Control experiments indicated that, compared with tetrabutylammonium, monocationic chiral cinchoninium has a dramatic rate acceleration effect on catalytic permanganate oxidation. We gratefully acknowledge the financial support from Nanjing Tech University (Start-up Grant No. 38274017100), National Natural Science Foundation of China (Nos. 21901115 and 21802018), Natural Science Foundation of Jiangsu Province (No. BK20190663), High-level Innovation and Entrepreneurship Talents Introduction Program of Jiangsu Province of China.

Background. Long noncoding RNAs (lncRNAs) have critical regulatory functions in biological and pathological activities during osteosarcoma progression. It is important to elucidate the expression pattern and reveal the underlying mechanisms of the newly identified lncRNAs. Methods. Herein, we screened the differentially expressed lncRNAs in osteosarcoma tumors and cell lines using lncRNA microarray. The candidate lncRNA was further verified by qRT-PCR, and the association of gene expression with clinicopathological features was evaluated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The targeting miRNA was identified using starBase analysis, and the competing endogenous RNA (ceRNA) network was established by STRING. Overexpression and silence of RNA were detected by qRT-PCR. Osteosarcoma cell proliferation was measured with CCK-8 assay, and the migration and invasion were evaluated with Transwell assay. Colony formation assay was observed. Flow cytometry evaluated the cell cycle. Western blot was performed to detect the mitotic markers and apoptosis-related proteins. A nude mouse tumor formation experiment was used to evaluate osteosarcoma progression in vivo. Cooverexpressing miR-34b-3p with RAD51 reversed the miR-34b-3p-induced changes in proliferation, the cell cycle, the expression of H2A.X, and that of apoptosis-related proteins. Results. HCG9 was identified as osteosarcoma-associated lncRNA. Osteosarcoma tissues and cell lines expressed higher levels of HCG9 as compared to normal tissues and osteoblasts, and high expression of HCG9 was further proved to be related to metastasis and the grade of osteosarcoma in clinical cases. Knockdown of HCG9 inhibited the proliferation, migration, and invasion of osteosarcoma cells. miR-34b-3p was identified as the target of HCG9, and RAD51 acted as a potential target of miR-34b-3p. Cooverexpressing miR-34b-3p with HCG9 partially suppressed the HCG9-stimulated proliferation, migration, and invasion of osteosarcoma cells in vitro and delayed the tumor progression in vivo. Conclusion. We discovered that lncRNA HCG9 promoted the proliferation of osteosarcoma cells via suppressing miR-34b-3p. Our study provides novel biomarkers and potential therapeutic targets for osteosarcoma treatment.

Background Thyroid dysfunction is suggested to be associated with diabetes, but it is not clear if the thyroid hormone levels are associated with diabetes in euthyroid adults. Objective To investigate the association between thyroid hormone levels and diabetes in euthyroid adults. Methods Among the euthyroid adults who underwent health examination in West China Hospital, Sichuan University in 2016, patients with diabetes were identified according to the medical history, fasting blood glucose and HbA1c. Age and sex matched controls were identified from the population. The patients with diabetes group was further divided into two subgroups: patients with newly diagnosed diabetes (NDD) and with previously diagnosed diabetes (PDD). Independent t-test and multivariate logistic regression models were used to investigate the difference on the levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and the ratio of FT4/FT3 between groups. Results We included 32,557 participants, 2,271 with diabetes and 1,187 NDD. Compared to the patients without diabetes, the odds ratios (ORs) per one unit of TSH, FT4, FT4/FT3 ratio and FT3 in patients with diabetes were 0.88 [95% confidence interval (CI): 0.82-0.95], 1.11 (95% CI: 1.08-1.14), 2.05 (95%CI: 1.81-2.32) and 0.85 (95%CI: 0.78-0.93), respectively. Compared to NDD group, the ORs per one unit of TSH, FT4, FT4/FT3 ratio and FT3 of the PDD group were 0.81 (95%CI: 0.71-0.92), 1.08 (95%CI: 1.04-1.12), 1.76 (95%CI: 1.49-2.08) and 1.01 (95%CI: 0.92-1.12), respectively. Conclusion In euthyroid adults, diabetes and its duration were significantly associated with thyroid hormone turnover. Patients with a previously diagnosed diabetes may be more likely to present elevated FT4/FT3 ratio, indicating an adaptive change of thyroid gland.

Hazardous metal pollution became a severe environmental issue in China. An efficient precipitation-flotation process was developed to achieve fast removal for metal-ions from wastewater. Structure and strength of precipitate particles/flocs significantly influence the flotation removal of metal-ions. Formation and growth-evolution of precipitate flocs in precipitate flotation were studied by stage analysis of precipitate particles-formation, flocs-regulation and flotation separation. The results demonstrate that early formed precipitates MHA(humics-metal complexing particles) have small particle size, high fractal dimension, low strength and recovery factor. The addition of Fe3+ and CTAB(cetyl trimethyl ammonium bromide) reagents make the precipitate particles aggregated to flocs(MHA-Fe, MHA-Fe-CTAB) much more large, loose, coarse, and small-density. The final generated MHA-Fe-CTAB flocs are hard to be broken up, easy to be recovered and efficient to be separated by flotation process. The flotation removal of MHA-Fe-CTAB flocs is clearly higher than that of MHA or MHA-Fe. The flotation results of MHA-Fe-CTAB are as follows: flotation removal of 98.7 ± 0.40%–99.9 ± 0.10%, residual TOC of 0.96 ± 0.38–1.35 ± 0.41 mg/L and turbidity of 0.44 ± 0.09–0.63 ± 0.16 NTU. Introducing Fe3+ and CTAB reagents into flotation solution contributes to the growth-evolution of precipitate flocs, which could intensify the metal-ions removal via precipitate flotation process and result in more ideal purification indexes for metal-containing wastewater.

Background: OIP5-AS1 has been reported to be aberrantly expressed in multiple cancers and associated with clinical outcomes. We conducted this study to assess the generalized prognostic val...

Additional file 1: Figure S1. Forest plots describing subgroup analysis of HRs for association between MIR31HG expression and OS based on follow-up months (a) and expression pattern of MIR31HG in cancerous tissues and matched normal samples in various cancers (b, c). CI confidence interval, HR hazard ratio, OS overall survival

To explore the reparative effects of DHA on the gut microbiome disturbance and dysfunctional lipid metabolism caused by long-term antibiotic therapy, it was tested on an azithromycin (AZI) mouse antibiotic model. Thirty specific-pathogen-free BALB/c mice (SPF grade, half male and half female) were randomly separated into three groups (n = 10, 5 male and 5 female): control group (CK), azithromycin natural recovery group (AZI) and DHA group (DHA). High-throughput sequencing and bioinformatics methods were used to analyze the gut microbiome. ELASE kits were used to measure blood lipid, lipids in the liver, and bile salt hydrolase (BSH) levels in feces. Gas chromatography and UPLC-MS/MS were employed to detect DHA and bile acids contents in liver, respectively. Real-time polymerase chain reaction (RT-PCR) was used to measure the expression of key enzymes involved in lipid metabolism. Long-term AZI treatment led to dyslipidemia, gut microbiome disturbance and anxious behaviors in the mouse model. DHA was found to significantly improve the dyslipidemia and anxiety-like behaviors induced by AZI. DHA had no effect on the structure of gut microbiome and bile acids contents but increased the content of the metabolic enzyme BSH in gut microbiota and normalized the expression of enzymes involved in lipid metabolism.

BACKGROUND: Regional lymph node involvement is thought to be rare in patients with chondrosarcoma, but its actual prevalence is unclear. Additionally, it is often not considered when prognostic factors are analyzed in patients with chondrosarcoma. However, it has been well established that lymph node involvement is a poor prognostic marker in patients with many types of bone and soft tissue sarcoma, including rhabdomyosarcoma, osteosarcoma, and Ewing’s sarcoma. Although lymph node metastases are rare among all sarcoma types, it is important to consider whether lymph node metastases should be assessed in patients with chondrosarcoma because these metastases may impact survival. QUESTIONS/PURPOSES: (1) What is the reported prevalence of regional lymph node involvement in patients with chondrosarcoma? (2) Do patients who have chondrosarcomas with regional lymph node involvement have different clinicopathologic presentations and survival than patients without regional lymph node involvement? (3) Is regional lymph node involvement independently associated with prognosis in patients with chondrosarcoma? METHODS: The data of patients with chondrosarcoma registered in the Surveillance Epidemiology and End Results database (SEER) (1988-2015) were analyzed for the reported prevalence of regional lymph node involvement and its relationship with clinicopathologic features and the 5-year overall survival rate. From 1988 to 2015, 5528 patients with chondrosarcoma were registered in the SEER database. After screening by the inclusion criterion—chondrosarcoma as the first primary tumor, diagnosis with histology confirmation, patients with active followup and available information about regional node status—3374 patients met the inclusion criteria and were analyzed. Demographics and clinicopathologic data were compared using chi-square or Fisher’s exact tests. Logistic regression analysis was used to assess the adjusted odds ratio. The overall survival rate was estimated with Kaplan-Meier curves and log-rank tests. Univariate and multivariate analyses of overall survival were performed with Cox proportional hazard models. In addition, a series of sensitivity analyses were performed to assess the robustness of the final Cox proportional hazard model. RESULTS: Forty-four patients (1.3%) were recorded in the database as having regional lymph node involvement at the time of the primary diagnosis. Lymph node metastases were more likely to be reported in an extraskeletal primary site (3% [13 of 426] versus 1% [31 of 2948], adjusted odds ratio [OR] = 2.9, 95% CI, 1.5–5.8; p = 0.003) for bone primary sites and tumors with maximum diameter ≥ 8 cm (2% [26 of 1045] versus 1% [10 of 1075], adjusted OR = 2.9, 95% CI, 1.3–6.3; p = 0.008) and poorer differentiation (4% [24 of 608] versus 1% [14 of 2308], adjusted OR = 4.0, 95% CI, 2.0–8.2; p < 0.001), and in those with distant metastases (7% [14 of 203] versus 1% [30 of 3148], adjusted OR = 3.5, 95% CI, 1.7–7.1, p = 0.001). The 5-year overall survival rates of patients with and without regional lymph node involvement were 28% (95% CI, 15–42%) and 77% (95% CI, 75–78%), respectively (p < 0.001). After controlling for age, sex, race, grade, metastatic status, size, and histologic subtype, the presence of regional lymph node involvement was associated with poorer survival (hazard ratio, 2.20; 95% CI, 1.50–3.24; p < 0.001); this finding was confirmed in several sensitivity analyses. CONCLUSION: The prevalence of regional lymph node involvement in patients with chondrosarcoma was 1.3% in the SEER database. Although chondrosarcomas are rare, patients with chondrosarcomas who have regional node metastases have a poorer prognosis than those who have not reported to have them. This may underrepresent the true proportion of patients with lymph node metastases given the inaccuracies of reporting in this database, but we believe these findings indicate that clinicians should examine patients more carefully for chondrosarcoma with lymph node metastases. Future studies are needed to assess potential treatment strategies to improve the prognosis of these patients. LEVEL OF EVIDENCE: Level III, prognostic study.

Homeobox B7 (HOXB7), a member of the HOX gene family, plays a role in tumorigenesis. However, until now the expression status and role of HOXB7 in osteosarcoma remain unclear. Therefore, the present study aimed to investigate the functional role and mechanism of HOXB7 in osteosarcoma. Our results demonstrated that HOXB7 was overexpressed in osteosarcoma cell lines. Downregulation of HOXB7 significantly inhibited osteosarcoma cell proliferation in vitro, as well as attenuated xenograft tumor growth in vivo. Downregulation of HOXB7 also inhibited the migration and invasion of osteosarcoma cells. Furthermore, downregulation of HOXB7 significantly suppressed the protein expression levels of p-PI3K and p-Akt in U2OS cells. In summary, our data demonstrated that downregulation of HOXB7 inhibited proliferation, invasion, and tumorigenesis, partly through suppressing the PI3K/Akt signaling pathway in osteosarcoma cells. Our findings provide new insights into the role of HOXB7 in osteosarcoma and new therapeutic targets for the treatment of osteosarcoma.

Salvianolic acid B (Sal B) is a water-soluble phenolic compound derived from Salvia Miltiorrhiza. Recent studies show Sal B has a clear function of anti-cerebral ischemia injury, which is closely related to antioxidation, free radical scavenging, neuroprotection and the blood brain barrier. The aim of the present study was to verify whether Sal B prevents steroid-induced osteonecrosis of the femoral head and to investigate its underlying pharmacological mechanisms. Steroid-induced osteonecrosis rat models were established to evaluate the effects of Sal B on osteonecrotic changes and repair processes. The use of Sal B improved steroid-induced histopathological scores and inhibited osteoclast differentiation in rats. Notably, Sal B induced bone marrow-derived mesenchymal stem cells into osteogenesis. Moreover, Sal B treatment suppressed peroxisome proliferator-activated receptor (PPAR)γ and AP2 protein expression levels and increased runt-related transcription factor 2 and Collagen I protein expression levels in steroid-induced rats. osteocalcin and alkaline phosphatase content in steroid-induced rats was enhanced by treatment with Sal B. These results suggest that Sal B prevents steroid-induced osteonecrosis of the femoral head via PPARγ expression in rats. The present pilot study provides a brief insight into the effect of Sal B on steroid-induced osteonecrosis.

Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a rare gastric mesenchymal entity with a peculiar plexiform pattern, bland spindle cells and myxoid stroma rich in arborizing blood vessels. Here we report a 44-year-old Chinese woman with PAMT. Initially she was admitted for removal of a gastric antral‘polyp’ found on a routine examination 5 months previously. Our gastroscopy showed a 0.8 × 0.8 cm polyp-like mass in the antrum which protruded into the lumen. Endoscopic submucosal dissection (ESD) was performed to remove this mass en bloc. The specimen was carefully examined by pathologists, and the correct diagnosis of PAMT was finally made. The tumor in this case depicted typical histopathological and immunohistochemical features of gastric PAMT. This PAMT was not only the smallest on endoscopic examination in the literature but also—unlike the already reported PAMTs—exhibited a focal hyperechogenic lesion on endoscopic ultrasonography (EUS). This information highlights its value on how to identify a PAMT at its early stage.

Cartilage calcification contributes to the development and progression of osteoarthritis (OA). It has been well-investigated adiponectin regulates vascular calcification. The purpose of this study is to investigate the therapeutic value and the molecular mechanism of AdipoRon, an adiponectin receptor agonist, on the chondrocytes calcification. Primary chondrocytes were isolated and cultured from normal cartilage and OA cartilage. The calcification in tissues was evaluated by inductively coupled plasma/atomic emission spectroscopy and alizarin red S staining. The calcification in chondrocytes was determined using the alkaline phosphatase (ALP) staining and an ALP assay kit. The cellular effects of AdipoRon were assessed by immunofluorescence staining and Western blot analysis. We found that calcification was significantly increased in OA cartilage tissues and cells. Importantly, the degree of calcification and ALP activity of the OA chondrocytes was decreased upon the treatment with AdipoRon. The AdipoRon-induced cellular effects, including the reduction of the calcification of chondrocytes and improvement of autophagy, were blocked by dorsomorphin, an 5'-adenosine monophosphate-activated protein kinase (AMPK) inhibitor. Moreover, autophagy activation by AdipoRon was mediated by the AMPK-mammalian target of rapamycin (mTOR) signaling pathway. Our results suggest that AdipoRon significantly alleviates the calcification of OA chondrocytes via activating AMPK-mTOR signaling to promote autophagy. Therefore, AdipoRon could be a potential therapeutic agent for the prevention and treatment of OA.

Mycotoxins are low-molecular-weight secondary metabolites produced by different fungal species, which can cause teratogenic, hepatotoxic, nephrotoxic, carcinogenic, hemorrhagic, and immunosuppressive effects, and damage the reproductive system in humans and other mammals. Mycotoxins are often present at low concentrations in the matrices and present a branch of compounds, homologs, and isomers. Vegetable oil is one of the top mycotoxin-contaminated foods. Vegetable oil contains lipids, fatty acids, and pigments, which have the potential to increase matrix effects and damage instruments. Therefore, the establishment of high-efficient sample pretreatment methods, and highly sensitive and high-throughput detection techniques are big challenges for the accurate determination of various mycotoxins in vegetable oil. In the present study, the current status and development trends of mycotoxin detection methods in different vegetable oils have been reviewed. Different pretreatment methods such as liquid-liquid extraction, solid phase extraction, gel permeation chromatography, dynamic covalent hydrazine chemistry, and QuEChERS are also summarized. Additionally, characteristics of detection techniques such as gas chromatography, liquid chromatography, tandem mass spectrometry, and immunosensors are discussed.

Background and Aims. A growing body of research has demonstrated that the degeneration of chondrocytes is the primary cause of osteoarthritis (OA). Parathyroid hormone-related protein (PTHrP) can alleviate the degeneration of chondrocytes via promotion of chondrocyte proliferation and inhibition of terminal differentiation, but the underlying mechanism remains unknown. This study aimed to identify the microRNAs (miRNAs) that may target PTHrP and regulate the proliferation and terminal differentiation of chondrocytes. Methods. Bioinformatic analysis was used to predict which miRNAs target PTHrP. We collected human knee cartilage specimens to acquire the primary chondrocytes, which we then used to test the expression and function of the targeted miRNAs. To explore the effects of miR-15a-5p on the putative binding sites, specific mimics or inhibitors were transfected into the chondrocytes. Furthermore, a dual-luciferase reporter gene assay and chondrocyte degeneration-related factors were used to verify the possible mechanism. Results. The expression of PTHrP was upregulated in the OA chondrocytes, whilst miR-15a-5p was downregulated in the OA chondrocytes. A negative correlation was observed between PTHrP and miR-15a-5p. The knockdown of miR-15a-5p promoted the growth of chondrocytes and inhibited calcium deposition, whilst overexpression of miR-15a-5p reversed this trend. The effect of miR-15a-5p overexpression was neutralised by PTHrP. Dual-luciferase reporter assays revealed that PTHrP can be used as a novel targeting molecule for miR-15a-5p. Conclusions. miR-15a-5p promotes the degeneration of chondrocytes by targeting PTHrP and, in addition to helping us understand the development of OA, may be a potential biomarker of OA.

Gastrointestinal stromal tumor (GIST) is a common sarcoma of gastrointestinal tract (GIT) with high metastatic and recurrence rates, but the proteomic features are still less understood. Here we performed systematic quantitative proteome profiling of GIST from 13 patients classified into very low/low, intermediate and high risk subgroups. An extended cohort of GIST (n = 131) was used for immunohistochemical validation of proteins of interest. In total, 9177 proteins were quantified, covering 55.9% of the GIT transcriptome from The Human Protein Altas. Out of the 9177 quantified proteins, 4930 proteins were observed in all 13 cases with 517 upregulated and 187 downregulated proteins in tumorous tissues independent of risk stage. Pathway analysis showed that the downregulated proteins were mostly enriched in metabolic pathway, whereas the upregulated proteins mainly belonged to spliceosome pathway. In addition, 131 proteins showed differentially expressed patterns among GIST subgroups with statistical significance. The 13 GIST cases were classified into 3 subgroups perfectly based on the expression of these proteins. The intensive comparison of molecular phenotypes and possible functions of quantified oncoproteins, tumor suppressors, phosphatases and kinases between GIST subgroups was carried out. Immunohistochemical analysis of the phosphatase PTPN1 (n = 117) revealed that the GIST patients with high PTPN1 expression had low chances of developing metastasis. Collectively, this work provides valuable information for understanding the inherent biology and evolution of GIST.

Artificial sweeteners have been widely used as replacements for sugars in foods. Rapid determination of artificial sweeteners contained in various foods are highly desirable for the routine analysis. Here, we report a robust approach based on direct analysis in real time coupled with QTRAP mass spectrometry to screen and quantitate simultaneously seven artificial sweeteners, including aspartame, saccharin, acesulfame-K, neotame, sucralose, cyclamate and alitame in alcoholic drinks. The detection method merely involved a simple sample pretreatment process, with a good linearity, low limit of quantification, satisfied recovery and relative standard deviation for each target compound. More importantly, the approach is highly sensitive and accurate in monitoring the seven artificial sweeteners in whisky, Chinese liquors, beer and wines obtained from the supermarket. The results demonstrated that the approach described here could be suitable for large-scale application in routine quality control analysis of artificial sweeteners.

Software-defined networking (SDN) has the ability to flexibly configure the network and is widely used in various scenarios. In SDN, different applications require the controller to deploy corresponding flow entries to maintain the effectiveness of network. However, the matching field range covered by entries of different applications may overlap, and when actions specified by these overlapping entries are inconsistent, conflicts may occur. Such conflicts may cause the flow to match the wrong entry, thereby affecting the correct expression of application functions. The scheme we proposed in this paper will be able to detect and resolve conflicts between flow entries. Firstly, we discussed the causes of conflicts, and then classified various conflict situations. This classification will help us to adopt different ways of resolving different types of conflicts and make the resolution of conflicts more targeted. Next, we propose a conflict detection algorithm based on B+ tree. This algorithm can detect different types of conflicts. According to theoretical proof, the use of B+ tree compared with other similar structures better in the performance of the time and space complexity. Finally, for the detected conflicting entries, we propose a conflict resolution scheme based on the failure degree of the flow entry according to the characteristics of SDN services tending to be more detailed. Through experimental evaluation, our scheme can effectively detect and resolve conflicts with lower overhead.

A self-separating, analyte-compatible, and efficient clean-up method for QuEChERS extracts was designed and developed based on dispersive solid-phase extraction using a branched polyethylenimine and nanoscale CaSO4 functionalized carboxylated multi-walled carbon nanotubes (MWCNTs) nanohybrids as sorbent. The feasibility of using a self-separating strategy based on the functionalization of sorbent in a purification procedure was analyzed for the first time in this study. Compared to the traditional QuEChERS method, the proposed method is rapid and convenient without centrifugation of numerous samples in the clean-up process. The use of nanohybrids overcame the issue of low recoveries for planar pesticides, which are easily adsorbed using MWCNTs. A better clean-up capability of the nanohybrids to remove matrix interferences and reduce matrix effect was demonstrated compared with that of traditional clean-up sorbent primary secondary amine. The method was validated by determining twenty-eight pesticides in cucumber, cabbage, apple, and orange. Limits of detections were in the range of 0.0001−0.0026 mg/kg. Spike recoveries of pesticides were within 75.3 − 113.6%, with relative standard deviations less than 14.3% at levels 0.01 mg/kg and 0.1 mg/kg. The developed method was successfully applied to monitor the multi-residues.

Lower back pain (LBP) is a common and remitting problem. One of the primary causes of LBP is thought to be degeneration of the intervertebral disc (IVD). The aim of the present study was to investigate the role of the myeloid differentiation primary-response protein 88 (MyD88)-dependent Toll-like receptor 4 (TLR4) signal pathway in the mechanism of IVD degeneration. IVD nucleus pulposus cells isolated and cultured from the lumbar vertebrae of Wistar rats were stimulated by various doses of lipopolysaccharide (LPS; 0.1, 1, 10 and 100 µg/ml) to simulate IVD degeneration. Cells were rinsed and cultured in serum-free Dulbecco's modified Eagle's medium/F12. Reverse transcription-quantitative polymerase chain reaction was used to determine the levels of TLR4, MyD88, tumor necrosis factor α (TNFα), and interleukin-1β (IL-1β) mRNA expression after 1, 3, 6, 9 and 12 h of incubation. Additionally, western blot and enzyme-linked immunosorbent assay analyses were used to determine the levels of TLR4, MyD88, TNFα, and IL-1β protein expression after 24, 48 and 72 h of incubation. The levels of TLR4, MyD88, TNFα and IL-1β mRNA all increased in the cells stimulated by 10 µg/ml LPS at 3, 6 and 9 h (all P

The incidence of thyroid carcinoma has obviously been rising throughout the world during the past ten years.

Cu-Ni-Fe-Mo-xCr type alloy coatings with different Cr content were produced on a medium carbon steel substrate by laser cladding in this investigation. The effect of Cr content on macro-quality, microstructure, phase structure and high temperature oxidation resistance of the coatings was revealed by macro photography, optical microscopy (OM), environmental scanning electron microscopy (ESEM) incorporating with EDX microanalysis, X-ray diffraction (XRD) analysis, respectively. Results showed that, the coatings with Cr content ranging from 0 to and 5 wt% are smooth and crack free while the coatings with Cr content ranging from 7.5 to and 10 wt% are smooth but cracked. The volume content of second phase (Fe,Ni,Si,Cr)2Mo and the high temperature oxidation resistance of the coatings are both increased with an increase in Cr content.

ZnO with hierarchical microspheres and hexagonal prisms structures were successfully synthesized by hydrothermal microemulsion route. Based on X-ray diffraction and scanning electron microscopy observation of the products at the different reaction time periods, the formation mechanism of three-dimensional hierarchical ZnO microspheres was proposed. Ultraviolet and visible diffuse reflectance spectra indicated that as-synthesized ZnO microspheres had enhanced absorption in both ultraviolet and visible light areas. The photocatalytic activities of as-synthesized products were evaluated by monitoring the degradation of methylene blue solution. Due to the synergistic effects of the high crystallization and special hierarchical structure, the hierarchical ZnO microsphere exhibited the highest photocatalytic activity.