OGT-induced O-GlcNAcylation of NEK7 protein aggravates osteoarthritis progression by enhancing NEK7/NLRP3 axis.

BACKGROUNDS: The role of O-GlcNAc transferase (OGT)-induced O-linked N-acetylglucosaminylation (O-GlcNAcylation) has been reported in multiple human diseases. However, its specific functions in osteoarthritis (OA) progression remain undetermined. OBJECTIVE: This study focused on the target proteins of OGT-induced O-GlcNAcylation in OA and the specific functional mechanism. METHODS: The levels of total O-GlcNAc and OGT were measured in both in vitro and in vivo OA models using western blot. The effects of OGT knockout on OA progression were detected through Safranin O staining, immunohistochemical staining and OARSI score evaluation. The effects of OGT silencing on LPS-induced chondrocyte injury were assessed by performing loss-of function assays. Co-immunoprecipitation (co-IP) was conducted to verify the effect of OGT-induced O-GlcNAcylation on the interaction between NEK7 and NLRP3. The role of OGT in modulating the O-GlcNAcylation and phosphorylation levels of NEK7 was analysed using western blot. RESULTS: The OGT-indued O-GlcNAcylation level was increased in both in vitro and in vivo OA models. Knockout of OGT mitigated OA progression in model mice. Additionally, silencing of OGT suppressed LPS-induced chondrocyte pyroptosis. Moreover, silencing of OGT inhibited the O-GlcNAcylation and enhanced the phosphorylation of NEK7 at S260 site, thereby blocking the binding of NEK7 with NLRP3. CONCLUSION: OGT-induced NEK7 O-GlcNAcylation promotes OA progression by promoting chondrocyte pyroptosis via the suppressing interaction between NEK7 and NLRP3.

Air pollutants, genetic susceptibility, and the risk of incident gastrointestinal diseases: A large prospective cohort study.

A comprehensive overview of the associations between air pollution and the risk of gastrointestinal (GI) diseases has been lacking. We aimed to examine the relationships of long-term exposure to ambient particulate matter (PM) with aerodynamic diameter ≤2.5 µm (PM2.5), 2.5-10 µm (PMcoarse), ≤10 µm (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx), with the risk of incident GI diseases, and to explore the interplay between air pollution and genetic susceptibility. A total of 465,703 participants free of GI diseases in the UK Biobank were included at baseline. Land use regression models were employed to calculate the residential air pollutants concentrations. Cox proportional hazard models were used to evaluate the associations of air pollutants with the risk of GI diseases. The dose-response relationships of air pollutants with the risk of GI diseases were evaluated by restricted cubic spline curves. We found that long-term exposure to ambient air pollutants was positively associated with the risk of peptic ulcer (PM2.5 : Q4 vs. Q1: hazard ratio (HR) 1.272, 95% confidence interval (CI) 1.179-1.372, NO2: 1.220, 1.131-1.316, and NOx: 1.277, 1.184-1.376) and chronic gastritis (PM2.5: 1.454, 1.309-1.616, PM10 : 1.232, 1.112-1.366, NO2: 1.456, 1.311-1.617, and NOx: 1.419, 1.280-1.574) after Bonferroni correction. Participants with high genetic risk and high air pollution exposure had the highest risk of peptic ulcer, compared to those with low genetic risk and low air pollution exposure (PM2.5: HR 1.558, 95%CI 1.384-1.754, NO2: 1.762, 1.395-2.227, and NOx: 1.575, 1.403-1.769). However, no significant additive or multiplicative interaction between air pollution and genetic risk was found. In conclusion, long-term exposure to ambient air pollutants was associated with increased risk of peptic ulcer and chronic gastritis.

Insights into momentous aroma dominating the characteristic flavor of jasmine tea.

Jasmine tea is loved by most people who drink flower tea owing to its unique aroma, and it is known as the top of flower teas. In our study, the quantitative evaluation of the quality of jasmine tea and detection of aroma components were carried out. First, the flavor quality of 92 kinds of jasmine tea was evaluated using multiple sub-factor quality evaluation methods. According to the evaluation results, jasmine tea was divided into three types: "fresh and lovely" (FL), "heavy and thick" (HT), and "fresh and heavy" (FH). Gas chromatography-mass spectrometry (GC-MS) was used to detect the aroma components of the three types of jasmine tea samples. α-Farnesene, cis-3-hexenyl benzoate, acid phenylmethyl ester, linalool, methyl anthranilate, and indole were the main substances that constituted the basic aroma quality characteristics of jasmine tea. Compared to the FL type, the HT and FH types were weaker in the diversification of the characteristic aroma and accumulation of green, herb, sweet, and roast aroma substances. Green and herb aromas play crucial roles in the fresh and persistent qualities of the three types of jasmine tea, which are the key quality factors research focus of jasmine tea.

A rare case of human taeniasis caused by Taenia saginata with species undetermined cysticercosis.

Taeniasis and cysticercosis, which are caused by Taenia saginata, Taenia solium and Taenia asiatica, are zoonotic parasitic infections with a significant disease burden worldwide. There is consensus amongst experts that T. saginata is a common tapeworm that causes taeniasis in humans as opposed to cysticercosis. This case study of a middle-aged Tibetan man conducted in 2021 challenges the prevailing notion that T. saginata exclusively causes taeniasis and not cysticercosis by documenting symptoms and laboratory studies related to both taeniasis and multiple cysticercosis. The patient's medical record with the symptoms of taeniasis and cysticercosis was reviewed, and the tapeworm's proglottids and cyst were identified from the patient by morphological evaluation, DNA amplification and sequencing. The patient frequently experienced severe headaches and vomiting. Both routine blood screenings and testing for antibodies against the most common parasites were normal. After anthelmintic treatment, an adult tapeworm was found in feces, and medical imaging examinations suggested multiple focal nodules in the brain and muscles of the patient. The morphological and molecular diagnosis of the proglottids revealed the Cestoda was T. saginata. Despite the challenges presented by the cyst's morphology, the molecular analysis suggested that it was most likely T. saginata. This case study suggests that T. saginata infection in humans has the potential to cause human cysticercosis. However, such a conclusion needs to be vetted by accurate genome-wide analysis in patients with T. saginata taeniasis associated with cysts. Such studies shall provide new insights into the pathogenicity of T. saginata.

Dynamic changes in the diversity and function of bacterial community during black tea processing.

Among all types of tea, black tea is produced in the largest amount worldwide, and its consumption is still increasing. Enzymatic fermentation is considered majorly contribute to quality formation of black tea, and the information about the roles of bacterial community in black tea processing is scarce. This study aimed to analyze the dynamic changes in composition, structure, and function of microbial communities during black tea processing and reveal the roles of bacterial community in black tea processing. Results showed that the genera Sphingomonas and Variovorax were dominant throughout the processing of black tea. Prediction function analysis of bacterial community showed that the mean proportions of glucuronoarabinoxylan endo - 1,4 - beta - xylanase, aminopeptidase B, phosphoserine phosphatase, homoserine O-acetyltransferase, glycolysis related enzymes, pyruvate dehydrogenase, tricarboxylic acid cycle related enzymes, and glyoxylate bypass were significantly elevated in the rolling and fermentation stages. The contents of amino acids, soluble sugar, theaflavins, thearubigins, and theabrownins increased greatly during the rolling and fermentation processes. Redundancy and Pearson's correlation analyses showed that the relative abundance of bacteria was closely related to the contents of water extract, tea polyphenols, epigallocatechin, epicatechin gallate, catechin gallate, thearubigins, theaflavins, and theabrownins. Overall, the findings provided new insights into the variation of bacterial community during black tea processing and improved our understanding of the core functional bacteria involved in black tea processing.

Uneven Index: A Digital Biomarker to Prompt Demodex Blepharitis Based on Deep Learning.

Purpose: To evaluate ocular surface manifestations and morphological changes in meibomian glands (MGs) based on artificial intelligence (AI) analysis in patients with Demodex blepharitis. Methods: In this retrospective study, 115 subjects were enrolled, including 64 subjects with Demodex blepharitis and 51 subjects without Demodex blepharitis as control group. Morphological indexes were evaluated for height, width, tortuosity, MG density, total variation, and the three types of corrected total variation as Uneven indexes. Results: There were no statistically significant differences in all MGs' average tortuosity and width between the two groups. The average height of all MGs and MG density were significantly lower in the Demodex blepharitis group than control group. The total variation and two types of Uneven indexes were significantly higher in the Demodex blepharitis group than in the control group. Especially the Uneven Index of total variation/MG density had an AUC of 0.822. And the sensitivity and specificity were 59.4% and 92.2%, respectively, at a cut-off value of 3971.667. In addition, Demodex blepharitis was associated with significantly lower meibum quality and expressibility, severe atrophy of MGs, a higher ocular surface disease index (OSDI), and more instability of the tear film. Conclusion: Demodex mites are strongly associated with morphological changes in the MGs and may cause uneven gland atrophy. Therefore, the novel characteristic parameter, the Uneven index, may serve as a digital biomarker to evaluate uneven atrophy of MGs and prompt Demodex blepharitis.

Long non-coding RNA-small nucleolar RNA host gene 7 regulates inflammatory responses following spinal cord injury by regulating the microRNA-449a/TNF-α-induced protein 3-interacting protein 2 axis.

The current study aimed to explore the anti-inflammatory effects of long non-coding RNA-small nucleolar RNA host gene 7 (lncRNA-SNHG7) and its mechanism in spinal cord injury (SCI) models. SCI models were established both in vivo and in vitro. Reverse transcription-quantitative PCR was performed to determine the expression levels of lncRNA-SNHG7 in SCI models. Bioinformatics analysis and dual-luciferase reporter assays were carried out to confirm the interaction between lncRNA-SNHG7 with microRNA (miR)-499a and TNF-α-induced protein 3-interacting protein 2 (TNIP2). In addition, cell viability, apoptosis, and the secretion of inflammatory cytokines were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow cytometric analysis, and enzyme linked immunosorbent assay (ELISA), respectively. The results showed that lncRNA-SNHG7 was markedly downregulated in the SCI model group. LncRNA-SNHG7 directly bound to miR-499a, which in turn directly targeted TNIP2. In addition, TNIP2 was significantly decreased in SCI rats and lipopolysaccharide (LPS)-treated PC-12 cells. The in vitro results in PC-12 cells revealed that lncRNA-SNHG7 overexpression attenuated neuronal cell death and SCI-mediated inflammatory responses by regulating miR-449a expression. Furthermore, miR-499a knockdown inhibited LPS-induced PC-12 cell injury by targeting TNIP2. In conclusion, lncRNA-SNHG7 modulates the apoptosis and inflammation of PC-12 cells by regulating the miR-449a/TNIP2/NF-κB signaling pathway.

LIM mineralization protein-1 inhibits IL-1ß-induced human chondrocytes injury by altering the NF-κB and MAPK/JNK pathways.

Osteoarthritis (OA) is a common degenerative disease that is associated with the degradation of articular cartilage. Accumulating evidence has confirmed that LIM mineralization protein-1 (LMP-1) is an important agent of bone formation and has been shown to be osteoinductive in various types of disease. However, the underlying mechanisms of LMP-1 in the pathogenesis of OA remain unknown. The present study aimed to evaluate the role and potential mechanism of LMP-1 in IL-1ß-stimulated OA chondrocytes. CHON-001 cells were transfected with pcDNA3.1-LMP-1, pcDNA3.1, negative control-small interfering (si)RNA or LMP-1 siRNA for 24 h and then induced by IL-1ß for 12 h to establish an OA model in vitro. Cell viability, apoptosis and inflammatory cytokine (IL-6, IL-8 and TNF-α) release were assessed using MTT assay, flow cytometry and ELISA, respectively. The expression levels of LMP-1, cleaved-caspase 3, phosphorylated (p)-p65, p65, p-JNK and JNK were analyzed using reverse transcription-quantitative PCR and western blotting. Overexpression of LMP-1 notably alleviated the IL-1ß-induced inflammatory response in CHON-001 cells, as shown by increased cell viability, decreased apoptosis, suppressed expression of cleaved-caspase 3 and a decreased cleaved-caspase 3/caspase 3 ratio. Moreover, IL-1ß-induced secretion of IL-6, IL-8 and TNF-α in CHON-001 cells; this was reversed by pcDNA3.1-LMP-1. However, knocking down LMP-1 expression exert opposite effects on the IL-1ß-induced inflammatory response in CHON-001 cells, as evidenced by the decreased cell viability, increased apoptosis, enhanced expression of cleaved-caspase 3 and cleaved-caspase 3/caspase 3 ratio and enhanced secretion of IL-6, IL-8 and TNF-α observed. The present data demonstrated that LMP-1 siRNA notably inhibited LMP-1 expression, suppressed cell viability, promoted apoptosis and enhanced cleaved-caspase 3 expression and cleaved-caspase 3/caspase 3 ratio. In addition, LMP-1 siRNA promoted the release of inflammatory factors in CHON-001 cells. It was also found that pcDNA3.1-LMP-1 inhibited p-p65 and p-JNK expression, as well as decreasing the p-p65/p65 and p-JNK/JNK ratio. Nevertheless, there was no significant difference in the mRNA expression levels of p65 and JNK between the groups. Taken together, these findings indicated that overexpression of LMP-1 alleviated IL-1ß-induced chondrocytes injury by regulating the NF-κB and MAPK/JNK pathways, suggesting that LMP-1 may be a valuable therapeutic agent for OA treatment.

Family Resilience, Parenting Styles and Psychosocial Adjustment of Children With Chronic Illness: A Cross-Sectional Study.

Objectives: To evaluate the level of parent-reported family resilience, parenting styles and psychosocial adjustment of children with chronic illness and to identify the relationships between family resilience, parenting styles and psychosocial adjustment in families with children with chronic illness. Methods: A cross-sectional study was conducted between June 2019 and August 2019. A total of 236 parents of children with chronic illness and 98 parents with healthy children were recruited from general hospitals by convenience sampling. A parent completed the Chinese Family Resilience Assessment Scale, the Parenting Rearing Patterns Questionnaire and the Strengths and Difficulties Questionnaire. Family resilience, parenting styles, and psychosocial adjustment of children with chronic illness were compared with those of healthy children. Structural Equation Modeling (SEM) was performed to explore the mediation effect of parenting styles between family resilience and psychosocial adjustment among children with chronic illness. Results: Parents of children with chronic illness reported lower level of family resilience and authoritative parenting, but more peer relationship problems compared to parents of healthy children. SEM showed that authoritative parenting fully mediated the relationship between family resilience and psychosocial adjustment of children with chronic illness. Conclusion: Childhood chronic illness reduces family resilience, authoritative parenting and children's psychosocial adjustment, but authoritative parenting mediated these effects, so authoritative parenting may be important for family resilience in families of children with chronic illness. Pediatric clinicians and nurses should provide family-centered interventions, as well as parenting training, to improve children's psychosocial outcomes.

The unreasonable use of high beam at nighttime among motor vehicle drivers / 预防医学

Objective@#To observe the incidence of unreasonable use of high beam at nighttime among motor vehicle drivers, so as to provide the evidence for the prevention and control of road traffic injury. @*Methods@#Four roads into city and five urban roads were selected in Yongkang of Zhejiang Province. An automatic recording system was used to collect the unreasonable use of high beam among motor vehicle drivers on the selected roads from 19:00 to 5:00 on Monday, Wednesday, Friday and Sunday during a week in July 2020. The regression tree model was used to analyze the relationship of the unreasonable use of high beam with road, time and traffic flow. @*Results@# A total of 89 989 motor vehicles were observed, and 2 419 motor vehicle drivers had unreasonable use of high beam, with an incidence rate of 2.69%. The incidence rate of the unreasonable use of high beam was 3.14% in the roads into city, which was higher than 2.30% in the urban roads ( P<0.05 ). The incidence rates of the unreasonable use of high beam in the roads into city and in the urban roads were 5.15% and 2.90% on Wednesday, which were higher than those on Monday ( 2.89% and 2.34% ), Friday ( 2.90% and 1.92% ) and Sunday (2.06% and 2.12%). The highest incidence rate of the unreasonable use of high beam in the roads into city was 6.07% between 4:00 and 5:00, and in the urban roads was 4.50% between 2:00 and 3:00. The results of regression tree classification analysis showed that the highest incidence rate was 8.13% on the roads into city in the east, west and south directions, and on the urban roads in the east and north directions with less than 317 vehicles per hour on Wednesday. @*Conclusion@#It is more likely for motor vehicle drivers to use high beams unreasonably at nighttime on the roads into city with less traffic flow.

Lupeol inhibits osteosarcoma progression by up-regulation of HMGA2 via regulating miR-212-3p.

BACKGROUND: Osteosarcoma (OS) is a common severe illness globally. Lupeol has been reported to participate in the pathophysiologic properties of various cancers, including OS. This study aimed to explore the effects of lupeol on proliferation, invasion, and apoptosis on OS cells and the underlying mechanism. METHODS: The cell viability of OS cells was determined by 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The expression levels of miR-212-3p and high-mobility group AT-hook 2 (HMGA2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in OS cells. The cell apoptosis and invasion were detected by flow cytometry and transwell invasion assays, respectively. The functional target of miR-212-3p was predicted by online software and confirmed by luciferase reporter assay. The protein level of HMGA2 was measured by western blot analysis. RESULTS: Lupeol suppressed cell viability and invasion, and promoted apoptosis by upregulating the expression of miR-212-3p in OS cells. Knockdown of miR-212-3p restored the anti-tumor effect of lupeol. Interestingly, miR-212-3p directly targeted HMGA2 and suppressed its expression. Moreover, HMGA2 reversed the inhibited impact on viability and invasion, and the promoted effect on apoptosis induced by upregulation of miR-212-3p. Also, lupeol administration exerts its anti-tumor effect by overexpression of miR-212-3p to suppress the expression of HMGA2 in OS cells. CONCLUSION: Lupeol inhibited OS progression by modulating the miR-212-3p/HMGA2 axis in vitro.

Ferric Ion Induction of Triggering Receptor Expressed in Myeloid Cells-2 Expression and PI3K/Akt Signaling Pathway in Preosteoclast Cells to Promote Osteoclast Differentiation.

OBJECTIVE: Iron plays a significant role in multiple biological processes. The purpose of this study was to measure whether iron mediated osteoclast differentiation through regulation of triggering receptor expressed in myeloid cells-2 (Trem-2) expression and the PI3K/Akt signaling pathway. METHODS: The effects of six different concentrations of ferric ammonium citrate (FAC) (100, 80, 40, 20, 10 and 0 µmol/L) on RAW 264.7 cells proliferation were assessed by Cell Counting Kit-8 (CCK-8) gassay. Tartrate resistant acid phosphatase (TRAP) assay was performed to detect the effects of FAC on osteoclast formation. The expression of osteoclast differentiation-related (TRAP, NFATc-1, and c-Fos) and Trem-2 mRNA and proteins was analyzed by reverse transcription-polymerase chain reaction and western blot, respectively. Si-Trem-2 was constructed and transfected to RAW264.7 to measure the effects of Trem-2 on FAC-mediated osteoclast formation. TRAP assay and osteoclast differentiation-related gene analyses were further performed to identify the role of Trem-2 in osteoclastogenesis. The Search Tool for the Retrieval of Interacting Genes (STRING) was used to explore the target genes of Trem-2. Trem-2-related gene ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used for further in-depth analysis. PI3K/Akt pathway-related proteins were detected by immunofluorescence and western blot. RESULTS: In groups with FAC concentration of 10 (102.5 ± 3.1), 20 (100.5 ± 1.5), and 40 µmol/L (98.7 ± 3.1), compared with the control group (100.1 ± 2.2), cell viability was not significantly different from the control (P > 0.05). When the concentration of FAC exceeded 80 µmol/L, cell viability was significantly decreased (87.5 ± 2.8 vs 100.1 ± 2.2, P < 0.05). FAC promotes Trem-2 expression and osteoclast differentiation in a dose-response manner (P < 0.05). The number of osteoclast-like cells was found to be reduced following transfection with the siRNA of Trem-2 (42 ± 3 vs 30 ± 5, P < 0.05). We observed that most of Trem-2 target genes are primarily involved in response to organic substance, regulation of reactive oxygen species metabolic process, and regulation of protein phosphorylation. The STRING database revealed that Trem-2 directly target two gene nodes (Pik3ca and Pik3r1), which are key transcriptional cofactors of the PI3K/Akt signaling pathway. KEGG pathways include the "PI3K-Akt signaling pathway," the "thyroid hormone signaling pathway", "prostate cancer," the "longevity regulating pathway," and "insulin resistance." Expression of p-PI3K and p-Akt protein, measured by immunofluorescence and western blotting, was markedly increased in the FAC groups. Trem-2 siRNA caused partial reduction of these two proteins (p-PI3K and p-Akt) compared to the FAC alone group. CONCLUSION: The FAC promoted osteoclast differentiation through the Trem-2-mediated PI3K/Akt signaling pathway. However, its regulation osteoclastogenesis should be verified through further in vivo studies.

Transmissibility of acute haemorrhagic conjunctivitis in small-scale outbreaks in Hunan Province, China.

Acute haemorrhagic conjunctivitis (AHC) outbreaks are reported frequently in China. However, the transmissibility of AHC remains unclear. This study aimed to calculate the transmissibility of the disease with and without interventions. An AHC outbreak dataset from January 2007 to December 2016 in different schools was built in Hunan Province. A Susceptible-Infectious-Recovered (SIR) model was adopted to calculate the effective reproduction number (Reff) of AHC. Reff was divided into two parts (Runc and Rcon) where Runc and Rcon represent the uncontrolled and controlled Reff , respectively. Based on Runc and Rcon, an index of effectiveness of countermeasures (Ieff) was developed to assess the effectiveness of countermeasures in each outbreak. During the study period, 34 AHC outbreaks were reported in 20 counties of 9 cities in Hunan Province, with a mean total attack rate of 7.04% (95% CI: 4.97-9.11%). The mean Runc of AHC outbreaks was 8.28 (95% CI: 6.46-10.11). No significance of Runc was observed between rural and urban areas (t = -1.296, P = 0.205), among college, secondary, and primary schools (F = 0.890, P = 0.459), different levels of school population (F = 0.738, P = 0.538), and different number of index cases (F = 1.749, P = 0.180). The most commonly implemented countermeasures were case isolation, treatment, and health education, followed by environment disinfection, symptom surveillance, and school closure. Social distance, prophylaxis, and stopping eye exercises temporary were implemented occasionally. The mean value of Rcon was 0.16 (range: 0.00-1.50). The mean value of Ieff was 97.16% (range: 71.44-100.00%). The transmissibility of AHC is high in small-scale outbreaks in China. Case isolation, treatment, and health education are the common countermeasures for controlling the disease.

Influencing Factors and Theoretical Models for the Surface Topography in Diamond Turning Process: A Review.

In this work, the influencing factors and corresponding theoretical models for the surface topography in diamond turning process are reviewed. The surface profile on one tool feed is the elementary unit of surface topography. The influences coupled with the models of the duplication effect of the tool edge profile, material spring back, and plastic side flow are outlined in this part. In light of the surface profile on one tool feed and "trim principle", the modeling methods of surface topography along the radial direction (2D surface topography) are commented. Moreover, the influence of the vibration between the diamond tool and workpiece on the 2D surface topography is discussed, and the theoretical models are summarized. Finally, the issues for modeling of 3D surface topography, particularly the influences of material defects, are analyzed. According to the state-of-the-art surface topography model of the diamond turned component, future work in this field is therefore predicted.

Identification of a novel miRNA-target gene regulatory network in osteosarcoma by integrating transcriptome analysis.

Osteosarcoma remains a leading cause of cancer death in children and young adolescents. Although the introduction of multiagent chemotherapy, survival rates have not improved in two decades. Therefore, it is urgently needed to know the details regarding molecular etiology to driving therapeutic inroads for this disease. In this study we performed an integrated analysis of miRNA and mRNA expression data to explore the dysregulation of miRNA and miRNA-target gene regulatory network underlying OS. 59 differentially expressed miRNAs were identified, with 28 up-regulated and 31 down-regulated miRNAs by integrating OS miRNA expression data sets available. Using miRWalk databases prediction, we performed an anticorrelated analysis of miRNA and genes expression identified by a integrated analysis of gene expression data to identify 109 differently expressed miRNA target genes. A novel miRNA-target gene regulatory network was constructed with the miRNA-target gene pairs. miR-19b-3p, miR-20a-5p, miR-124-3p and their common target CCND2, the nodal points of regulatory network, may play important roles in OS. Bioinformatics analysis of biological functions and pathways demonstrated that target genes of miRNAs are highly correlated with carcinogenesis. Our findings may help to understand the molecular mechanisms of OS and identify targets of effective targeted therapies for OS.

Low-grade myxofibrosarcoma following a metal implantation in femur: a case report.

Myxofibrosarcoma is a myxoid variant of malignant fibrous histiocytoma that most commonly involves the extremities of elderly people. However, a primary myxofibrosarcoma with bone invasion in young adults is extremely rare. Herein, we report the case of a 31-year-old male with a gradually enlarging left thigh mass, who had a history of left femur fracture and received an open reduction and internal fixation with titanium alloy plates and screws 33 months previously. Imaging investigations revealed an irregularly shaped soft tissue mass around the left femur shaft and a partial bone defect in the middle one-third of the left femur. Pathological examination of the resected specimen showed a multi-nodular appearance, abundant myxoid matrix and elongated curvilinear capillaries. Immunohistochemical studies revealed that the tumor cells was positive for VIM and MDM2, and was negative for CK, MSA, SMA, DES, S-100 and CD34. Labeling index of Ki-67 was 25%. Based on the morphological finding and immunostaining, it was diagnosed as a low-grade myxofibrosarcoma. The clinical and imaging examinations did not reveal the evidence of a primary cancer elsewhere, and the patient had no personal or family history of malignancy. To our knowledge, this is the first case of a primary myxofibrosarcoma developed following a fracture and metal implantation in young adults. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1745984882113605.

In vitro construction of tissue-engineered bone with bone morphogenetic protein-2-transfected rabbit bone marrow mesenchymal stem cells and hydroxyapatite nanocomposite.

OBJECTIVE: The aim of this study was to investigate the adenovirus-mediated human bone morphogenetic protein-2 (Ad-BMP-2) transfection of rabbit bone marrow mesenchymal stem cells (rBMSCs), which, together with hydroxyapatite nanocomposite (Nano-HA), were used to construct tissue-engineered bone in vitro. METHODS: Ad-BMP-2 adenovirus vector was prepared with the Gateway technique and was transfected into rBMSCs. Sol-flocculation method was employed to prepare Nano-HA. Immunohistochemistry, reverse transcription-polymerase chain reaction, and Western blot assay were performed to detect the BMP-2 expression in transfected cells. At 48 h after transfection, transfected cells were inoculated into the Nano-HA scaffold. After 3 and 5 days, scanning electron microscopy was performed to observe adherence and growth of these cells. The cells in the scaffold were harvested after digestion, and Western blot assay was performed to detect the BMP-2. RESULTS: After transfection, the mRNA and protein of hBMP-2 were expressed at a high level. Scanning electron microscopy indicated that these cells were evenly distributed in the scaffold, with favorable adherence. In addition, the cells collected from the scaffold had a high expression of BMP-2. CONCLUSIONS: Adenovirus-mediated hBMP-2 transfection was successfully performed in rBMSCs, and these cells inoculated into the Nano-HA scaffold had a high expression of hBMP-2 in the scaffold. Thus, this technique is feasible to construct tissue-engineered bone in vitro.

Association analyses of osteoprotegerin gene polymorphisms with bone mineral density in Chinese postmenopausal women.

Osteoprotegerin gene (OPG) is an important candidate gene of osteoporosis. The objective of this study was to evaluate the association between OPG gene polymorphisms and bone mineral density (BMD). A total of 336 Chinese postmenopausal women were included in this study. OPG gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), created restriction site-PCR (CRS-PCR) and DNA sequencing methods. BMD was evaluated at the lumbar spine (L(2-4)), total hip and femoral neck. Two single-nucleotide polymorphisms (SNPs) (g.21775C>T and g.23367T>C) were identified and the association analysis showed significant difference of spine BMD among different g.23367T>C genotype, subjects with the genotype TT was significantly higher than those of genotype TC and CC. Such a significant difference was not observed at the neck hip BMD and total hip BMD. The g.21775C>T polymorphism was not significantly associated with spine BMD, total hip BMD and neck hip BMD in the studied subjects. These findings suggested that OPG gene polymorphisms were associated with BMD in Chinese postmenopausal women. Results from this study will be helpful in further studies to determine the role of OPG gene in osteoporosis.

Experimental study of nano-hydroxyapatite/recombinant human bone morphogenetic protein-2 composite artificial bone.

OBJECTIVE: To investigate the repairing ability of nano-hydroxyapatite/recombinant human bone morphogenetic protein-2 (Nano-HA/rhBMP-2) composite artificial bone for bone defect and to provide evidence for its application in clinical repair of bone defect. METHODS: The animal model of bone defect was made on unilateral radius of 90 New Zealand white rabbits, which were randomly divided into experimental group (group A, bone defect was repaired with Nano-HA/rhBMP-2 composite artificial bone), control group (group B, bone defect was repaired with Nano-HA artificial bone), and blank group (group C, bone defect was unrepaired). The repairing ability for bone defect was evaluated by gross observation, X-ray examination, scanning electron microscope, radionuclide bone imaging and biomechanical analysis at 4(th), 8(th), and 12th week postoperatively. RESULTS: Both Nano-HA/rhBMP-2 composite artificial bone and Nano-HA artificial bone could stimulate new bone formation, but the former could stimulate more new bone formation and had better repairing ability for bone defect than that of the latter, with statistically significant difference (P <0.05). CONCLUSION: Nano-HA/rhBMP-2 composite artificial bone has good repairing ability for bone defect and it is hopeful to become an ideal repairing material for bone defect.

Functional elucidation of MiR-34 in osteosarcoma cells and primary tumor samples.

MiR-34s have been characterized as direct p53 targets, which induce apoptosis, cell cycle arrest, and senescence. MiR-34s were found to associate with tumorigenesis. Thus far, there is no study on the role of MiR-34s in osteosarcoma. In the current study, we intensively investigated the function of MiR-34s in two osteosarcoma cell lines: U2OS (p53(+/+)) and SAOS-2 (p53(-/-)). We found that MiR-34s affect the expression of its target genes partially in a p53-dependent manner. And p53 also partially contributes to the MiR-34s induced cell cycle arrest and apoptosis. Finally, we examined the expression, genetic and epigenetic alterations of MiR-34 gene in 117 primary osteosarcoma samples. Expression of MiR-34s was decreased in tumor samples, and MiR-34 genes underwent minimal deletions and epigenetic inactivation in osteosarcomas.