Effect of Dimethyloxalylglycine on Stem Cells Osteogenic Differentiation and Bone Tissue Regeneration-A Systematic Review.

Dimethyloxalylglycine (DMOG) has been found to stimulate osteogenesis and angiogenesis of stem cells, promoting neo-angiogenesis in bone tissue regeneration. In this review, we conducted a comprehensive search of the literature to investigate the effects of DMOG on osteogenesis and bone regeneration. We screened the studies based on specific inclusion criteria and extracted relevant information from both in vitro and in vivo experiments. The risk of bias in animal studies was evaluated using the SYRCLE tool. Out of the 174 studies retrieved, 34 studies met the inclusion criteria (34 studies were analyzed in vitro and 20 studies were analyzed in vivo). The findings of the included studies revealed that DMOG stimulated stem cells' differentiation toward osteogenic, angiogenic, and chondrogenic lineages, leading to vascularized bone and cartilage regeneration. Addtionally, DMOG demonstrated therapeutic effects on bone loss caused by bone-related diseases. However, the culture environment in vitro is notably distinct from that in vivo, and the animal models used in vivo experiments differ significantly from humans. In summary, DMOG has the ability to enhance the osteogenic and angiogenic differentiation potential of stem cells, thereby improving bone regeneration in cases of bone defects. This highlights DMOG as a potential focus for research in the field of bone tissue regeneration engineering.

Laparoscopic versus open surgical management in elderly patients with rectal cancer aged 70 and older.

Background: This retrospective study aimed to compare the short- and long-term surgical outcomes of laparoscopic surgery versus open surgery in elderly patients with rectal cancer. Patients and Methods: Elderly patients (≥70 years old) with rectal cancer who received radical surgery were retrospectively analysed. Patients were matched (1:1 ratio) using propensity score matching (PSM), with age, sex, body mass index, American Society of Anesthesiologists score and tumour-node-metastasis staging included as covariates. Baseline characteristics, post-operative complications, short- and long-term surgical outcomes and overall survival (OS) were compared between the two matched groups. Results: Sixty-one pairs were selected after PSM. Patients with laparoscopic surgery had a longer duration of operation time, lower estimated blood loss, shorter duration of post-operative analgesics administered, time to first flatus, time to first oral diet and post-operative hospitalisation stay than those observed in patients with open surgery (All P < 0.05). The incidence of post-operative complications in the open surgery group was numerically higher than that occurred in the laparoscopic surgery group (30.6% vs. 17.7%). Median OS was 67.0 months (95% confidence interval [CI], 62.2-71.8) in the laparoscopic surgery group and 65.0 months (95% CI, 59.9-70.1) in the open surgery group, however, Kaplan-Meier curves indicated that no significant differences in OS (Log-rank test, P = 0.535) were noted between the two matched groups. Conclusions: Compared with the open surgery, laparoscopic surgery had the advantages of less trauma and faster recovery, and provided similar long-term prognostic outcome in elderly patients with rectal cancer.

ATP6V1H deficiency impairs glucose tolerance by augmenting endoplasmic reticulum stress in high fat diet fed mice.

Vacuolar H+-ATPase (V-ATPase) is a ubiquitous proton pump that mediates the proton transmembrane transportation in various cells. Previously, H subunit of V-ATPase (ATP6V1H) was found to be related with insulin secretion and diabetes. However, the mechanism by which ATP6V1H regulates insulin secretion and glucose metabolism remains unclear. Herein, we established a high-fat-diet (HFD) fed model with Atp6v1h+/- mice and detected the expression and secretion of insulin and some biochemical indices of glucose metabolism, in order to explore the related mechanisms in ß-cells. Transcriptome sequencing, qPCR and western blot analysis showed that ATP6V1H deficiency worsened fatty acid-induced glucose tolerance impairment by augmenting endoplasmic reticulum stress in ß-cells, and alternative splicing of ATP6V1H might be involved in this process. These results indicated that ATP6V1H deficiency increased the susceptibility to T2DM.

The sensing mechanism of fluorescent probe for PhSH and the process of ESIPT.

The detection mechanism of fluorescent probe FQ-DNP (DNP: 2,4-dinitropheno) for PhSH and the detailed ESIPT process of its product 2-(6-(diethylamino) quinolin-2-yl)-3-Hydroxy-4H-chromen-4-one (FQ-OH) have been revealed by density functional theory (DFT) and time-dependent density functional theory (TD-DFT). For FQ-OH, the decreased bond length of H6-N7 and RDG analysis illustrate that the strength of hydrogen bond H6-N7 has been enlarged after photoexcitation, creating a good condition for ESIPT. To illustrate the ESIPT process in detail, the potential energy curves are performed and the transition state reaction energy is calculated. In the S0 state, the FQ-OH could happen proton transfer (PT) to form keto, but the keto form is more unstable than enol form. After photoexcitation, in the S1 state, FQ-OH could happen PT to produce stable keto form. Excited dynamic simulation shows that PT happens at 71.5 fs. The calculated absorption and emission spectra are in agreement with the experimental data, and the calculated Stokes shift is 160 nm. Frontier molecular orbitals (FMOs) and hole-electron analysis show that twisted intramolecular charge transfer (TICT) is responsible for the fluorescent quenching of FQ-DNP.

A Method of Domain Dictionary Construction for Electric Vehicles Disassembly.

Currently, there is no domain dictionary in the field of electric vehicles disassembly and other domain dictionary construction algorithms do not accurately extract terminology from disassembly text, because the terminology is complex and variable. Herein, the construction of a domain dictionary for the disassembly of electric vehicles is a research work that has important research significance. Extracting high-quality keywords from text and categorizing them widely uses information mining, which is the basis of named entity recognition, relation extraction, knowledge questions and answers and other disassembly domain information recognition and extraction. In this paper, we propose a supervised learning dictionary construction algorithm based on multi-dimensional features that combines different features of extraction candidate keywords from the text of each scientific study. Keywords recognition is regarded as a binary classification problem using the LightGBM model to filter each keyword, and then expand the domain dictionary based on the pointwise mutual information value between keywords and its category. Here, we make use of Chinese disassembly manuals, patents and papers in order to establish a general corpus about the disassembly information and then use our model to mine the disassembly parts, disassembly tools, disassembly methods, disassembly process, and other categories of disassembly keywords. The experiment evidenced that our algorithms can significantly improve extraction and category performance better than traditional algorithms in the disassembly domain. We also investigated the performance algorithms and attempts to describe them. Our work sets a benchmark for domain dictionary construction in the field of disassembly of electric vehicles that is based on the newly developed dataset using a multi-class terminology classification.

Ubiquitination of interleukin-1α is associated with increased pro-inflammatory polarization of murine macrophages deficient in the E3 ligase ITCH.

Macrophages play critical roles in homeostasis and inflammation. Macrophage polarization to either a pro-inflammatory or anti-inflammatory status is controlled by activating inflammatory signaling pathways. Ubiquitination is a posttranslational modification that regulates these inflammatory signaling pathways. However, the influence of protein ubiquitination on macrophage polarization has not been well studied. We hypothesized that the ubiquitination status of key proteins in inflammatory pathways contributes to macrophage polarization, which is regulated by itchy E3 ubiquitin ligase (ITCH), a negative regulator of inflammation. Using ubiquitin proteomics, we found that ubiquitination profiles are different among polarized murine macrophage subsets. Interestingly, interleukin-1α (IL-1α), an important pro-inflammatory mediator, was specifically ubiquitinated in lipopolysaccharide-induced pro-inflammatory macrophages, which was enhanced in ITCH-deficient macrophages. The ITCH-deficient macrophages had increased levels of the mature form of IL-1α and exhibited pro-inflammatory polarization, and reduced deubiquitination of IL-1α protein. Finally, IL-1α neutralization attenuated pro-inflammatory polarization of the ITCH-deficient macrophages. In conclusion, ubiquitination of IL-1α is associated with increased pro-inflammatory polarization of macrophages deficient in the E3 ligase ITCH.

Gallic acid-gold nanoparticles enhance radiation-induced cell death of human glioma U251 cells.

Glioblastoma multiforme (GBM) is among the most common adult brain tumors with invariably fatal character. Following the limited conventional therapies, almost all patients, however, presented with symptoms at the time of recurrence. It is dire to develop novel therapeutic strategies to improve the current treatment of GBM. Gallic acid is a well-established antioxidant, presenting a promising new selective anti-cancer drug, while gold nanoparticles (GNPs) can be developed as versatile nontoxic carriers for anti-cancer drug delivery. Here, we prepared gallic acid-GNPs (GA-GNPs) by loading gallic acid onto GNPs, reduction products of tetrachloroauric acid by sodium citrate, through physical and agitation adsorption. GA-GNPs, rather than GNPs alone, significantly inhibited the survival of U251 GBM cells, as well as enhanced radiation-induced cell death. Moreover, GA-GNPs plus radiation arrested the cell cycle of U251 at the S and G2/M phases and triggered apoptotic cell death, which is supported by increased BAX protein levels and decreased expression of BCL-2. Thus, GA-GNPs have great potential in the combination with radiation therapy in future studies for GBM treatment.

MiR-613 inhibits the proliferation, migration, and invasion of papillary thyroid carcinoma cells by directly targeting TAGLN2.

BACKGROUND: Papillary thyroid carcinoma (PTC), with a rapidly increasing incidence, is the most prevalent malignant cancer of the thyroid. However, its pathogenesis is unclear and its specific clinical indicators have not yet been identified. There is increasing evidence that microRNAs (miRNAs) play important roles in tumor occurrence and progression. Specifically, miR-613 participates in the regulation of tumor development in various cancers; however, its effects and mechanisms of action in PTC are still unclear. Therefore, in this study, we investigated the expression and function of miR-613 in PTC. METHODS: qRT-PCR was used to determine miR-613 expression in 107 pairs of PTC and adjacent-normal tissues as well as in PTC cell lines and to detect TAGLN2 mRNA expression in PTC tissues and adjacent normal tissues. Western blot analysis was performed to identify TAGLN2 and epithelial-mesenchymal transition (EMT) biomarkers. The effects of miR-613 on PTC progression were evaluated by performing MTS, wound-healing, and Transwell assays in vitro. Luciferase reporter assays were also performed to validate the target of miR-613. RESULTS: In PTC, miR-613 was significantly downregulated and its low expression level was associated with cervical lymph node metastasis. However, its overexpression significantly suppressed PTC cell proliferation, migration, and invasion and inhibited EMT. TAGLN2 was identified as a target of miR-613, which also significantly inhibited the expression of TAGLN2. Further, the restoration of TAGLN2 expression attenuated the inhibitory effects of miR-613 on PTC cell proliferation and metastasis. CONCLUSION: Our findings demonstrated that miR-613 can suppress the progression of PTC cells by targeting TAGLN2, indicating that miR-613 plays the role of a tumor suppressor in PTC. Overall, these results suggest that the upregulation of miR-613 is a promising therapeutic strategy for PTC.

Effect of VEGFC on lymph flow and inflammation-induced alveolar bone loss.

The lymphatic system plays a crucial role in the maintenance of tissue fluid homeostasis and the immunological response to inflammation. The effects of lymphatic drainage dysfunction on periodontitis have not been well studied. Here we show that lymphatic vessel endothelial receptor 1 (LYVE1)+ /podoplanin (PDPN)+ lymphatic vessels (LVs) are increased in the periodontal tissues, with accumulation close to the alveolar bone surface, in two murine periodontitis models: rheumatoid arthritis (RA)-associated periodontitis and ligature-induced periodontitis. Further, PDPN+ /alpha-smooth muscle actin (αSMA)- lymphatic capillaries are increased, whereas PDPN+ /αSMA+ collecting LVs are decreased significantly in the inflamed periodontal tissues. Both mouse models of periodontitis have delayed lymph flow in periodontal tissues, increased TRAP-positive osteoclasts, and significant alveolar bone loss. Importantly, the local administration of adeno-associated virus for vascular endothelial growth factor C, the major growth factor that promotes lymphangiogenesis, increases the area and number of PDPN+ /αSMA+ collecting LVs, promotes local lymphatic drainage, and reduces alveolar bone loss in both models of periodontitis. Lastly, LYVE1+ /αSMA- lymphatic capillaries are increased, whereas LYVE1+ /αSMA+ collecting LVs are decreased significantly in gingival tissues of patients with chronic periodontitis compared with those of clinically healthy controls. Thus, our findings reveal an important role of local lymphatic drainage in periodontal inflammation-mediated alveolar bone loss. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Predicting potential palliative care beneficiaries for health plans: A generalized machine learning pipeline.

Recognizing that palliative care improves the care quality and reduces the healthcare costs for individuals in their end of life, health plan providers strive to better enroll the appropriate target population for palliative care. Current research has not adequately addressed challenges related to proactively select potential palliative care beneficiaries from a population health perspective. This study presents a Generalized Machine Learning Pipeline (GMLP) to predict palliative needs in patients using administrative claims data. The GMLP has five steps: data cohort creation, feature engineering, predictive modeling, scoring beneficiaries, and model maintenance. It encapsulates principles of population health management, business domain knowledge, and machine learning (ML) process knowledge with an innovative data pull strategy. The GMLP was applied in a regional health plan using a data cohort of 17,197 patients. Multiple ML models were turned and evaluated against a custom performance metric based on the business requirement. The best model was an AdaBoost model with a precision of 71.43% and a recall of 67.98%. The post-implementation evaluation of the GMLP showed that it increased the recall of high mortality risk patients, improved their quality of life, and reduced the overall cost. The GMLP is a novel approach that can be applied agnostically to the data and specific ML algorithms. To the best of our knowledge, it is the first attempt to continuously score palliative care beneficiaries using administrative data. The GMLP and its use case example presented in the paper can serve as a methodological guide for different health plans and healthcare policymakers to apply ML in solving real-world clinical challenges, such as palliative care management and other similar risk-stratified care management workflows.

Thy1 is a positive regulator of osteoblast differentiation and modulates bone homeostasis in obese mice.

Thy1 (CD90), a glycosylated, glycophosphatidylinositol-anchored membrane protein highly expressed by subsets of mesenchymal stem cells and fibroblasts, inhibits adipogenesis. The role of Thy1 on bone structure and function has been poorly studied and represents a major knowledge gap. Therefore, we analyzed the long bones of wild-type (WT) and Thy1 knockout (KO) mice with micro-computed tomography (micro-CT) and histomorphometry to compare changes in bone architecture and overall bone structure. micro-CT analysis of long bones revealed Thy1 KO and WT mice fed a high-fat diet demonstrated bone structural parameters at 4 mo that differed significantly between WT and KO mice. A significant reduction in trabecular bone volume was noted in Thy1 KO mice. The most prominent differences were observed in trabecular bone volume ratio and trabecular bone connectivity density. Consistent with micro-CT measurements, histomorphometric analysis also showed decreased bone volume in the obese Thy1 KO mice compared to obese WT mice. In vitro assays revealed that osteogenic conditions increased Thy1 expression during OB differentiation and absence of Thy1 attenuated osteoblastogenesis. Together, these findings support the concept that Thy1 serves as a major mechanistic link to regulate bone formation and negatively regulate adipogenesis.-Paine, A., Woeller, C. F., Zhang, H., Garcia-Hernandez, M. L., Huertas, N., Xing, L., Phipps, R. P., Ritchlin, C. T. Thy1 is a positive regulator of osteoblast differentiation and modulates bone homeostasis in obese mice.

Relationship Between ADAMTS8, ADAMTS18, and ADAMTS20 (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) Expressions and Tumor Molecular Classification, Clinical Pathological Parameters, and Prognosis in Breast Invasive Ductal Carcinoma.

BACKGROUND The aim of this study was to investigate the correlations between ADAMTSs expression and breast invasive ductal carcinoma (IDC), and to offer a theoretical basis for novel treatment methods for IDC patients. MATERIAL AND METHODS Non-proliferative catheter of breast fibroadenoma (FA) and IDC were used as the normal control and experimental group, respectively. Immunohistochemical (IHC) staining and Western blot (WB) analysis was used to assess protein expression levels of ADAMTS8, ADAMTS18, and ADAMTS20 in both FA and IDC tissues. The results of IHC, the relationship between the protein expression and the tumor molecular classification, and clinical pathological parameters were all evaluated. RESULTS IHC and WB results showed that the expression of ADAMTS8/18 in IDC samples was higher than in FA samples, while the expression of ADAMTS20 in IDC samples was lower than that in FA samples. According to the results of WB, the level of ADAMTS8 was higher in the HER2+ group than in the HER2- group and FA group. The expression of ADAMTS18 in the HR+ (including ER+ and PR+) group was significantly higher than in the HR- group and FA group. The expression of ADAMTS18 protein was also higher in the Ki67+ group than in the Ki67- group. ADAMTS20 was higher in HER2+ IDC compared with the basal subtype of IDC. CONCLUSIONS ADAMTS8/18/20 levels were not significantly correlated to the molecular subtype of IDC. ADAMTS18/20 was significantly associated with histological grade of IDC. ADAMTS8 may predict poor prognosis results of IDC patients.

The chemokine receptor CXCR7 is a critical regulator for the tumorigenesis and development of papillary thyroid carcinoma by inducing angiogenesis in vitro and in vivo.

Papillary thyroid carcinoma (PTC) is a well-differentiated neoplasm, but it can transfer early to cervical lymph nodes. Accumulating evidences have confirmed the important roles of CXCR7 in tumor cell proliferation, invasion, metastasis, and angiogenesis. Our previous study demonstrated CXCR7 modulated proliferation, apoptosis, and invasion of PTC cells. In this study, we evaluated the effect of expression of CXCR7 in PTC cells on angiogenesis and whether its expression had an influence on the tumor growth of PTC in vivo. We evaluated the effect of CXCR7 on interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) secretion, angiogenesis, and tumor growth by ELISA, endothelial tube formation assay, and a xenograft tumor model in nude mice. Immunohistochemistry was used to assess expression of CD34 in tumor of mice. In vitro and in vivo studies in PTC cells suggested that the alteration of CXCR7 expression was correlated with angiogenesis and tumor growth. Moreover, CXCR7 mediated the expression of IL-8 and VEGF, which might be involved in the regulation of tumor angiogenesis. These findings suggest that CXCR7 affects the growth of PTC cells and participates in the tumorigenesis of PTC, probably through regulating angiogenesis by the proangiogenic VEGF or IL-8.

High-fat diet causes bone loss in young mice by promoting osteoclastogenesis through alteration of the bone marrow environment.

Obesity is a severe health problem in children, afflicting several organ systems including bone. However, the role of obesity on bone homeostasis and bone cell function in children has not been studied in detail. Here we used young mice fed a high-fat diet (HFD) to model childhood obesity and investigate the effect of HFD on the phenotype of cells within the bone marrow environment. Five-week-old male mice were fed a HFD for 3, 6, and 12 weeks. Decreased bone volume was detected after 3 weeks of HFD treatment. After 6 and 12 weeks, HFD-exposed mice had less bone mass and increased osteoclast numbers. Bone marrow cells, but not spleen cells, from HFD-fed mice had increased osteoclast precursor frequency, elevated osteoclast formation, and bone resorption activity, as well as increased expression of osteoclastogenic regulators including RANKL, TNF, and PPAR-gamma. Bone formation rate and osteoblast and adipocyte numbers were also increased in HFD-fed mice. Isolated bone marrow cells also had a corresponding elevation in the expression of positive regulators of osteoblast and adipocyte differentiation. Our findings indicate that in juvenile mice, HFD-induced bone loss is mainly due to increased osteoclast bone resorption by affecting the bone marrow microenvironment. Thus, targeting osteoclast formation may present a new therapeutic approach for bone complications in obese children.

[Expression of HIF-1α and correlation with angiogenesis in tissue of breast cancer complicated with diabetes].

OBJECTIVE: To explore the expression of hypoxia-inducible factor 1 alpha (HIF-1α) in tissue of breast cancer complicated with diabetes and examine the correlation with vascular endothelial growth factor (VEGF) and microvascular density (MVD). METHODS: The clinical data were collected by reviewing the relevant medical records. The difference of clinicopathologic features between breast cancer patients with diabetes (diabetic group) and that of those without diabetes (control group) was analyzed retrospectively. Immunohistochemical Streptavidin-Perosidase (SP) method was used to detect the expressions of HIF-1α and VEGF in breast cancer tissue of two groups.Vascular endothelial cells were tagged with CD31 to calculate MVD. RESULTS: The patients of tumor diameter > 2 cm were 68.4% (67/98) and lymphatic metastasis rate was 59.2% (58/98) in diabetes group. And those in control group were 54.2% (58/107) and lymphatic metastasis rate was 43.9% (47/107). The inter-group difference was significant (P < 0.05).HIP-1α was expressed in both groups. The positive rate of HIF-1α was 80.6% (79/98) in diabetes group versus 64.5% (69/107) in control group (P = 0.010). The positive rate of VEGF was 86.7% (85/98) in diabetes group versus 68.2% (73/107) in control group (P = 0.002). MVD value was 113.7 ± 32.0 in diabetes group versus 104.7 ± 29.4 in control group (P = 0.003). The positive rate of VEGF in HIF-1α positive patients of diabetes group was significantly higher than that in negative counterparts (91.1% vs 68.4%, P = 0.009). The values of MVD were 117.1 ± 30.3 and 99.5 ± 35.1 respectively in both groups. And the MVD value of HIF-1α positive group was significantly higher than that of negative group (P = 0.03). CONCLUSION: Diabetic complications may play critical roles in the development and metastasis of breast cancer through enhanced angiogenesis of tumor tissue.

Ubiquitin E3 ligase Itch negatively regulates osteoclast formation by promoting deubiquitination of tumor necrosis factor (TNF) receptor-associated factor 6.

Itch is a ubiquitin E3 ligase that regulates protein stability. Itch(-/-) mice develop an autoimmune disease phenotype characterized by itchy skin and multiorgan inflammation. The role of Itch in the regulation of osteoclast function has not been examined. We report that Itch(-/-) bone marrow and spleen cells formed more osteoclasts than cells from WT littermates in response to receptor activator of NF-κB ligand (RANKL) and was associated with increased expression of the osteoclastogenic transcription factors c-fos and Nfatc1. Overexpression of Itch in Itch(-/-) cells rescued increased osteoclastogenesis. RANKL increased Itch expression, which can be blocked by a NF-κB inhibitor. The murine Itch promoter contains NF-κB binding sites. Overexpression of NF-κB p65 increased Itch expression, and RANKL promoted the binding of p65 onto the NF-κB binding sites in the Itch promoter. Itch(-/-) osteoclast precursors had prolonged RANKL-induced NF-κB activation and delayed TNF receptor-associated factor 6 (TRAF6) deubiquitination. In WT osteoclast precursors, Itch bound to TRAF6 and the deubiquitinating enzyme cylindromatosis. Adult Itch(-/-) mice had normal bone volume, but they had significantly increased LPS-induced osteoclastogenesis and bone resorption. Thus, Itch is a new RANKL target gene that is induced during osteoclastogenesis. Itch interacts with the deubiquitinating enzyme and is required for deubiquitination of TRAF6, thus limiting RANKL-induced osteoclast formation.

Ubiquitin e3 ligase itch negatively regulates osteoblast differentiation from mesenchymal progenitor cells.

Itch, a HECT family E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of target proteins. However, the role of Itch in osteoblasts has not been investigated. We report that Itch(-/-) mice have significantly increased bone volume, osteoblast numbers, and bone formation rate. Using bone marrow stromal cells from Itch(-/-) mice and wild-type (WT) littermates as bone marrow mesenchymal precursor cells (BM-MPCs), we found that BM-MPCs from Itch(-/-) mice have compatible numbers of cells expressing mesenchymal stem cell markers. However, Itch(-/-) BM-MPCs grew faster in an in vitro culture, formed more CFU-F mesenchymal colonies, and exhibited increased osteoblast differentiation and decreased adipogenesis. Importantly, Itch(-/-) mesenchymal colony cells formed significantly more new bone in a tibial defect of recipient mice compared with WT cells. The expression levels of JunB, an AP-1 transcription factor that positively regulate osteoblast differentiation, were significantly increased in Itch(-/-) BM-MPCs when proteasome function is intact. In contrast, the amount of ubiquitinated JunB protein was markedly decreased in Itch(-/-) cells when proteasome function was blocked. Overexpression of WT Itch, but not an Itch ligase-inactive mutant, rescued differentiation defects of Itch(-/-) BM-MPCs. Itch(-/-) BM-MPCs had a similar role in immune modulation as WT cells. Thus, Itch negatively controls osteoblast differentiation from BM-MPCs through the regulation of proteasomal degradation of positive osteoblast regulator JunB protein. Itch is a potential new target for bone anabolic drug development to treat patients with bone loss.

The involvement of CXCR7 in modulating the progression of papillary thyroid carcinoma.

BACKGROUND: Although papillary thyroid carcinoma (PTC) has favorable prognosis, it is prone to cervical lymph node metastasis. Chemokine receptors play a role in metastasis of tumor cells, and accumulating evidence suggests an important role for the chemokine receptor CXCR7 in cancer development. We previously demonstrated high expression of CXCR7 protein in PTC tissue. In this study, we further evaluated the role of CXCR7 in PTC. METHODS: The expression of CXCR7 messenger RNA and protein in 79 cases of PTC and peritumoral tissues was detected by real-time quantitative polymerase chain reaction and Western blot. The association between CXCR7 expression and clinicopathologic characteristics in PTC was analyzed. Stable CXCR7 overexpression and knockdown PTC cells were constructed and used to examine proliferation, cell cycle, apoptosis and invasion of PTC cells by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, propidium iodide staining, 7-amino-actinomycin D staining, and invasion assay. We examined cell cycle regulatory protein levels by Western blot. RESULTS: CXCR7 messenger RNA and protein levels were markedly increased in PTC and correlated with tumor progression. CXCR7 could regulate proliferation, cell cycle, apoptosis, invasion, and the expression of cell cycle regulatory proteins involved in the S-G2 phase transition. Knockdown of CXCR7 in PTC cells suppressed cell proliferation and invasion, decreased expression of cyclin A, CDK2 and PCNA, increased expression of p21 and p57, induced S phase arrest, and promoted apoptosis. CONCLUSIONS: CXCR7 plays an important role in regulating growth and metastasis ability of PTC cell and provides a potential target for therapeutic interventions in PTC.

[Analysis of predictive factors affecting sentinel lymph node status in early breast cancer patients].

OBJECTIVE: To investigate the predictive factors affecting sentinel lymph node status in early breast cancer patients. METHODS: Clinicopathological data of 1 038 patients with early breast cancer, who underwent sentinel lymph node biopsy in Henan Tumor Hospital between July 2010 and August 2013, were reviewed. Logistic regression analysis was performed to identify the relevance of clinicopathological features with sentinel lymph node metastases. RESULTS: This group was consisted of 1 038 female patients with an average of 48.6 years. Positive sentinel lymph nodes were found in 22.9% (238/1 038) of the patients. The average number of sentinel lymph nodes removed by surgery was 3.8. Tumor size, tumor location, histopathology, ER/PR status and Ki-67 level were significantly correlated with SLN metastasis(P < 0.05 for all). All the above factors but Ki-67 level were significant independent predictors for SLN metastasis(P < 0.01 for all). CONCLUSION: Negative hormone receptor status, invasive cancer of non-specific histopathological type, tumor size >2 cm, and tumor location in the outer upper quadrat are independent predictive factors of sentinel lymph node metastasis in patients with early breast cancer.

[Efficacy of delayed administration of etanercept after spinal cord injury].

OBJECTIVE: To observe the effect of delayed administration of etanercept on the motor function, the expression of apoptosis-related genes and the pathological alterations of spinal cord in vivo in experimental murine model of spinal cord injury (SCI). METHODS: Seventy-two male adult SD rats were randomly divided into 6 groups, which were subjected to SCI induced by the application of vascular clips (force of 70 g) to the dura. Experimental groups (E1, E2, and E3 group) were given administration of etanercept immediately, 1 h, and 8 h after SCI. The control groups (C1, C2, and C3 group) were given administration of saline at the same time as experimental groups. Six rats of each group were killed 24 h after SCI in order to collect the samples for testing the expression of Bax and Bcl-2 by Western blot. The rest were killed 14 d after SCI for observing the pathological alteration using light microscopy. The recovery of motor function was graded using the modified murine Basso, Beattle, and Bresnahan (BBB). RESULTS: (1) The results of the expressions of Bax and Bcl-2 by Western blot: the gray value of the expression of Bax of E1 group was 165.423 ± 2.946, of E2 group 135.391 ± 3.045, of E3 group 108.543 ± 6.999, and of the control group 69.054 ± 0.774, and the gray value of the expression of Bcl-2 of E1 group was 58.854 ± 3.592, of E2 group 84.315 ± 2.138, of E3 group 125.091 ± 2.699, and of the control group 156.304 ± 2.490. (2) The results of BBB score: etanercept given immediately or 1 h after SCI could improve the recovery of the rats. There were significant differences in BBB score 14 d after SCI between E1 group (13.000 ± 1.095) and C1 group (7.167±0.753), E2 group (9.833 ± 1.472) and C2 group (7.000 ± 0.632) while there were no significant difference between E3 group (7.333 ± 0.516) and C3 group (6.833±0.753). (3) The result of histological alteration: histological alterations, such as necrosis, infiltration of lymphocytes and fibroblast and loss of nerve cells, were found attenuated in E1 and E2 groups, compared with C1 and C2 groups. There was no obvious difference between E3 and C3 groups. CONCLUSION: Administration of etanercept may inhibit the apoptosis after SCI, but this kind of effect may be too weak to improve the BBB score and histological alterations obviously when administration of etanercept is delayed 8 h after SCI. The clinical value of etanercept to SCI needs to be further validated.