Objective: To compare the differences and similarities among the system of quality of life instruments for cancer patients (QLICP) V1.0, the quality of life questionnaire (QLQ) from European Organization for Research and Treatment of Cancer (EORTC) and Functional Assessment of Cancer Therapy (FACT) from Center on Outcomes, Research and Education (CORE) of America. Methods: Based on literatures and our measuring data from patients at hospitals, the constructs, characteristics and psychometrics of the systems above were analyzed and compared. Internal consistency reliability was assessed using Cronbach α coefficient for each domain, and test-retest reliability through calculating the Pearson correlation coefficient r between the first and second assessments as well as intra-class correlation (ICC). Construct validity was evaluated by Pearson correlation coefficient r (item-domains correlations) and factor analysis. The criterion-related validity was evaluated by correlating corresponding domains of two instruments. Responsiveness was assessed through comparing the mean difference between the pre-treatment and post-treatment with standardized response mean (SRM). Results: The instruments of three systems were of different outstanding characteristics with all psychometrics meeting requirements. Measurements for 12 types of cancers showed that the internal consistency reliability Cronbach α coefficient for the overall scale of QLICP (V1.0) was 0.67-0.92, and for FACT was 0.79-0.98. The test-retest reliability (r or ICC) for the overall scale of QLICP (V1.0) was 0.61-0.99, and for FACT was 0.60-0.98. The SRM for the overall scale of QLICP (V1.0) was 0.25-1.28, and for FACT was 0.11-0.83. However, the QLICP was of better construct (clear hierarchical structure with items→facets→domains→overall) and Chinese culture. Conclusion The instruments of three systems can be used as the instruments to assess quality of life for patients with cancer with selections basing on different settings.

Objective To investigate the inhibitory effect of 188 Re-labeled BaGdF5-poly ( ethylene glycol) ( PEG) nanoparticles ( NPs) on hepatoma cells, and explore the application of the radiolabeled NPs for SPECT imaging. Methods BaGdF5-PEG NPs were synthesized by hydrothermal method, and were fur-ther radiolabeled with 188Re using diethylene triamine pentaacetic acid (DTPA) as a coupling agent. The human hepatoma cells SMCC 7721 were treated with different concentrations of BaGdF5-PEG NPs, 188 ReO-4 or 188Re-DTPA-BaGdF5 NPs (14.8, 74.0, 370.0×104 Bq/ml) for 24 h, and then the cell proliferation rates were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. 188ReO-4 and 188 Re-DTPA-BaGdF5 NPs were administrated into normal rabbits via the ear vein, respectively. For the former, static SPECT/CT imaging were performed at 30, 60 min post-injection, and for the latter, dynamic SPECT images were captured within 10 min, and static SPECT/CT images at 30, 60, 120 min post-injec-tion. The rabbit VX2 tumor model was established, and a microcatheter was inserted into hepatic artery via the rabbit femoral artery, and then the mixture of 188 Re-DTPA-BaGdF5 NPs and lipiodol was injected into the tumor region. SPECT/CT imaging for VX2 tumor was performed at 30 min later. Data were analyzed by two-sample t test. Results The BaGdF5-PEG NPs were nearly square and the particle size was about 10 nm. The labeling yield of 188 Re-DTPA-BaGdF5 was 94.1％ at the optimum conditions. Moreover, it showed high stability in vitro and in vivo. In vitro, BaGdF5-PEG NPs did not exhibit obvious cytotoxicity even at a high concentration. Both 188 ReO-4 and 188 Re-DTPA-BaGdF5 could inhibit the proliferation of SMCC 7721 cells, but 188 Re-DTPA-BaGdF5 showed a significantly stronger inhibitory effect at the doses of 74.0 and 370.0×104 Bq/ml ( t values:4.21,4.09, both P<0.01) . In vivo, 188 ReO-4 was absorbed by maxillary glands and was quickly elimi-nated from blood via the kidneys. The 188 Re-DTPA-BaGdF5 NPs mainly accumulated in the liver and spleen. In addition, retention and accumulation of 188 Re-DTPA-BaGdF5 NPs in the liver tumor could be achieved by using transarterial intervention technique for drug delivery. Conclusion 188Re-DTPA-BaGdF5 NPs have cer-tain killing effects on hepatoma cells in vitro, and with the help of transarterial intervention technique, the NPs can be aggregated within liver tumor, where they not only can be used for SPECT imaging, but also have potential therapeutic effects.

As a dioxygenase, Ten-Eleven Translocation 2 (TET2) catalyzes subsequent steps of 5-methylcytosine (5mC) oxidation. TET2 plays a critical role in the self-renewal, proliferation, and differentiation of hematopoietic stem cells, but its impact on mature hematopoietic cells is not well-characterized. Here we show that Tet2 plays an essential role in osteoclastogenesis. Deletion of Tet2 impairs the differentiation of osteoclast precursor cells (macrophages) and their maturation into bone-resorbing osteoclasts in vitro. Furthermore, Tet2 mice exhibit mild osteopetrosis, accompanied by decreased number of osteoclasts in vivo. Tet2 loss in macrophages results in the altered expression of a set of genes implicated in osteoclast differentiation, such as Cebpa, Mafb, and Nfkbiz. Tet2 deletion also leads to a genome-wide alteration in the level of 5-hydroxymethylcytosine (5hmC) and altered expression of a specific subset of macrophage genes associated with osteoclast differentiation. Furthermore, Tet2 interacts with Runx1 and negatively modulates its transcriptional activity. Our studies demonstrate a novel molecular mechanism controlling osteoclast differentiation and function by Tet2, that is, through interactions with Runx1 and the maintenance of genomic 5hmC. Targeting Tet2 and its pathway could be a potential therapeutic strategy for the prevention and treatment of abnormal bone mass caused by the deregulation of osteoclast activities.
5-Methylcytosine ; analogs & derivatives ; chemistry ; metabolism ; Animals ; Cell Differentiation ; Cells, Cultured ; Core Binding Factor Alpha 2 Subunit ; genetics ; metabolism ; DNA-Binding Proteins ; physiology ; Genome ; Genomics ; Mice ; Mice, Knockout ; Osteoclasts ; cytology ; metabolism ; Proto-Oncogene Proteins ; physiology

BACKGROUND:Our previous studies have found that polygonatum sibiricum polysaccharide (PSP) promotes osteogenic differentiation of bone marrow mesenchymal stem cel s (BMSCs) by Wnt/β-catenin signaling pathway, but the molecular mechanism is unclear.OBJECTIVE:To investigate the effect of PSP promoting the osteogenic differentiation via Wnt signaling pathways in BMSCs after LRP5 silencing. METHODS:LRP5 interference vectors were constructed and then transfected into C57BL/6 mouse BMSCs cultured in vitro. The transfection efficiency of cel s was calculated under fluorescence inverted microscope and the expression of LRP5 protein was detected by western blot assay. The osteogenic potential of BMSCs after LRP5-siRNA transfection was analyzed by alkaline phosphatase staining, alizarin red staining and western blot assay. Effect of PSP on the osteogenic differentiation of LIRP5-silenced mouse BMSCs was detected by real-time PCR and dual luciferase assay. RESULTS AND CONCLUSION:Compared with the control group, the mineralization ability, the mRNA expressions of Runx2 and Osterix, and the protein expression of LRP5 were significantly decreased in the LRP5-siRNA group (P<0.05). PSP could promote LRP5-siRNA transfected mouse BMSCs differentiating into osteoblasts and significantly upregulated the expressions ofβ-catenin and Osterixin, and also induced the high expression of luciferase reporter gene (TOPFlash) containing wild type TCF binding sites (P<0.05). To conclude, LRP5 plays an important role in the process of mouse BMSCs differentiating into osteoblasts. PSP can promote the osteogenic differentiation of mouse BMSCs by activating the Wnt/β-catenin signaling pathway independent on LRP5.

Objective:To investigate the effect of long-chain non-coding CDKN2B targeting miR-19 on the biological behavior of chronic myeloid leukemia cells and its mechanism.Methods: The expression of CDKN2B in different leukemia cells were detected by qPCR.Double luciferase reporter gene was used to detect the interaction between CDKN2B and miR-19.MTT proliferation assay and flow cytometry were used to detect the effect of CDKN2B on the proliferation and apoptosis of HL-60 cells.The changes of migration ability of leukemia HL-60 cells after overexpress of CDKN2B were detected by scratch test.The changes of invasion ability of leukemia HL-60 cells after silencing CDKN2B were detected by Transwell invasion assay.Scaling healing experiment and Transwell invasion assay were used to detect the effect of miR-19 on the migration and invasion of leukemia cells after silencing CDKN2B.The morphological changes of cytoskeleton microfilament microtubules after silencing CDKN2B were detected by phalloidin staining.Western blot was used to detect the expression of PI3K/AKT signaling pathway after silencing CDKN2B.Results: The expression level of CDKN2B was the lowest in leukemia cell HL-60.CDKN2B binds specifically to the 3′UTR of miR-19;overexpression of CDKN2B could inhibit the proliferation and enhance the apoptosis of leukemia HL-60 cells.Overexpression of CDKN2B can inhibit the invasion and migration of leukemia HL-60 cells.After overexpressed of CDKN2B,the cytoskeleton showed decreased pseudopodia and decreased exercise capacity.The expression of actin was down-regulated.The expression of PI3K/AKT pathway protein was down-regulated after overexpressed of CDKN2B.Conclusion: CDKN2B can target the regulation of miR-19 to regulate the biological behavior of leukemia cells.

BACKGROUND: Bone marrow-derived mononuclear cells (BM-MNCs) hold the potential of differentiating into osteoclasts. Polygonatum sibiricum polysaccharide (PSP) may inhibit the differentiation of BM-MNCs into osteoclasts and it is expected to become a new drug for the treatment of osteoporosis. OBJECTIVE: To investigate the effect of PSP on the differentiation of mouse BM-MNCs into osteoclasts induced by receptor activator of nuclear factor kappa-B ligand (RANKL) and bone resorption in vivo. METHODS: Mouse bone marrow-derived macrophages cultured in vitro, the effect of macrophage colony stimulating factor and PSP (5, 10, 20, 40, 80,160, 320, 640, 1280, 2560 mg/L) on the proliferation of mouse BM-MNCs was detected by cell counting kit-8 assay to determine the PSP concentration range; the mouse BMMs were cultured and induced in DMEM medium containing macrophage colony stimulating factor, RANKL and 5, 10, 20, 40, 80,160, 320, 640 mg/L PSP, respectively; those cultured without PSP served as control group. The morphological changes of cells were observed under an inverted microscope.; the number of osteoclasts was detected by tartrate-resistant acid phosphatase staining; the mRNA expression levels of osteoclast-related genes including tartrate-resistant acid phosphatase, matrix metalloproteinase-9, cathepsin K, and nuclear factor of activated T cells c1 were evaluated by quantitative real-time PCR. A mouse model of calvarial osteolysis induced by lipopolysaccharide was established to receive PSP intervention, and then micro CT scanning, three-dimensional reconstruction and relevants software were used for quantitative analysis of bone volume/volume percentage, trabecular number, trabecular bone spacing and thickness. The number of osteoclasts was identified by tartrate-resistant acid phosphatase staining and quantitative analysis of bone resorption area was conducted. RESULTS AND CONCLUSION: Compared with the control group, the concentration of PSP below 640 mg/L showed no significant effect on the proliferation of BMMs (P > 0.05). Different concentrations of PSP (40-640 mg/L) significantly reduced the number of osteoclasts, osteoclast differentiation and maturation, and the mRNA expression levels of tartrate-resistant acid phosphatase, matrix metalloproteinase-9, cathepsin K, and nuclear factor of activated T cells c1 TRAP, MMP-9, CtsK and NFATc1 (P < 0.05). Compared with lipopolysaccharide, PSP could effectively alleviate the lipopolysaccharide-induced calvarial osteolysis, and the bone volume/volume percentage, trabecular number, and trabecular bone spacing were significantly decreased (P < 0.05); additionally, the number of osteoclasts and the area of bone resorption were decreased significantly (P < 0.01). To conclude, PSP can inhibit the differentiation and maturation of mouse BMMs to osteoclasts and alleviate lipopolysaccharide-induced calvarial osteolysis.

Objective To investigate PSP on bone microstructures,Ca,P,OPG and RANKL of osteoporotic rat model.Methods Thirty female rats randomly divided into five groups:Sham,OVX,H-,M-,L-PSP.Sham and OVX were irrigated stomachsaline;PSP solution was gavaged to other groups.After 8-week,bone microstructures of tibial metaphyseal,Ca,P,OPG and RANKL were measured.Results Body weight,Ca,P,RANKL,Tb.Sp of OVX were significantly increased compared to Sham,OPG,BV/TV,Tb.Th,Tb.N decreased.Body weight of H-,M-PSP,Ca and Tb.Sp of PSP,P and RANKL in H-PSP were decreased compared to OVX,OPG in H-,M-PSP,BV/TV,Tb.Th,Tb.N of PSP group increased.The differences were statistically significant (P ＜ 0.05).Conclusion PSP prevents osteoporosis by improving the microstructure of trabecular bone,reducing bone turnover,increasing OPG and reducing RANKL expression.

Objective To investigate the correlativity between elasticity modulus and pathological severity in chronic pancreatitis (CP).Methods Twenty-one pigs were divided randomly into experimental group (n=18) and control group (n=3) using random number method.The main pancreatic duct (MPD) was incompletely ligated to establish the CP model.In control group, MPD was not ligated.The animals were killed in batches at 4th, 8th and 12th week after surgery.The pancreatic tissue was taken for elasticity modulus test and pathological examination, and the pigs were classified into control, mild, moderate and severe groups based on the severity of fibrosis.Cell density, fat infiltration and extracellular edema were observed and classified into mild and severe.The difference of elasticity modulus among different groups were compared by Variance analysis, the correlation between pancreatic fibrosis and elastic modulus was analyzed with Spearman correlation analysis, and ROC curve was used to evaluate its efficacy of diagnosing CP.Results Sixteen CP models were established successfully expected for 2 deaths (mild, n=7;moderate, n=2 and severe, n=7).All of the control group (n=3) showed normal pancreas.The elasticity modulus of control, mild and moderate to severe group were 0.4268±0.0566, 0.3203±0.0518 and 0.2235±0.0685, respectively.The difference between the groups was statistically significant (F=13.658,P<0.01), and the elastic modulus and pathological grade had a negative correlation (r=0.969, P<0.01).AUC of elasticity modulus for differentiating normal and mild CP was 1.000, the best critical value was 0.3807, and both the sensitivity and specificity of the diagnosis were 100%.AUC for differentiating mild and moderate to severe CP was 0.8730, the best critical value was 0.2646, and the sensitivity and specificity of the diagnosis were 85.7% and 77.8%, respectively.The pancreatic elasticity modulus of low parenchymal cell density group and high parenchymal cell density group were 0.1931±0.0373 and 0.3485±0.0655, respectively, which in the high cell density group was significantly higher than that in the low cell density group (t=-5.719, P<0.01).The elasticity modulus of negative infiltration or slight fatty infiltration group and severe fatty infiltration group were 0.3401±0.0697 and 0.1855±0.0344, respectively, which in the negative infiltration or slight infiltration group was significantly higher than that in severe infiltration group (t=5.102, P<0.01).The elasticity modulus of negative or mild cell edema group and moderate to severe cell edema group were 0.2760±0.0825 and 0.3024±0.1056, respectively;there was no statistically significant(t=-0.586, P >0.05).Conclusions The elasticity modulus can be used to detect the pathological changes of CP, and evaluate the CP pathologic grades.

OBJECTIVETo evaluate surgical outcomes and the feasibility of robotic thyroidectomy and central neck dissection (CND).

METHODSThe clinical data of 40 patients of papillary thyroid microcarcinoma underwent total thyroidectomy (or lobectomy and isthmusectomy) and CND using the Da Vinci system through axillo-bilateral-breast approach in Jinan Military General Hospital of People's Liberation Army from February to December 2014 were analyzed retrospectively (robotic group). Other forty patients of papillary thyroid microcarcinoma underwent total thyroidectomy (or lobectomy and isthmusectomy) and CND by open approach were selected as the control (open group). Cosmetic satisfaction was assessed after a month postoperation by the numerical score system. t-test and χ(2) test were used to compare the clinical characters, total operative time, intraoperative estimated blood loss, postoperative hospital stay, number of lymph nodes removed, visual analogue scale for pain, postoperative complications, and cosmetic effect between the 2 groups.

RESULTSAll 80 patients were diagnosed of papillary thyroid microcarcinoma. The total thyroidectomy (or lobectomy/isthmusectomy) with CND of 40 patients were successfully performed by da Vinci Si surgical system. The numbers of total thyroidectomy of robotic group and the open group were 36 and 37, respectively. The numbers of metastatic lymph nodes of robotic group and open group were 14 and 15, respectively. The operation time of the robotic group was (130±12) minutes, which was longer than that of open group (98±11) minutes (t=12.432, P<0.05). The study showed statistical significant difference between the two groups regarding the visual analog scale pain assessment (1.9±0.9 vs.3.9±1.1, t=8.900, P<0.05). There were no statistical significant difference of intraoperative estimated blood loss, postoperative hospital stay, number of lymph nodes removed, and the complication rate between the 2 groups.Postoperative cosmetic result was more satisfying on the robotic group (9.1±0.5) than open group (4.8±1.5) (t=17.200, P<0.05).

CONCLUSIONSThe robotic total thyroidectomy (or lobectomy and isthmusectomy) and CND has similar surgery safety and feasibility as open procedures. The robotic thyroidectomy is a good alternative surgical modality for patients with papillary thyroid microcarcinoma who wish to avoid neck scars.

Axilla ; Breast ; Carcinoma, Papillary ; surgery ; Humans ; Length of Stay ; Lymph Nodes ; Neck Dissection ; Operative Time ; Postoperative Complications ; Postoperative Period ; Retrospective Studies ; Robotic Surgical Procedures ; Thyroid Neoplasms ; surgery ; Thyroidectomy ; methods

BACKGROUND:Bone marrow mesenchymal stem cels (BMSCs) have the ability of multi-directional differentiation. Polygonatum sibiricum polysaccharide can promote osteogenetic differentiation of mouse BMSCs by activating Wnt/β-catenin signaling pathway, which is expected to become a new drug for the treatment of osteoporosis.
OBJECTIVE:To investigate the effects of Polygonatum sibiricum polysaccharide on Wnt/β-catenin signaling pathway in the osteogenic differentiation of mouse BMSCs.
METHODS:The mouse BMSCs were cultured and induced in osteoblast medium containing final concentrations (5, 10, 25, 50mg/L) of Polygonatum sibiricum polysaccharide. The mouse BMSCs treated without Polygonatum sibiricum polysaccharide was set as the negative control group. The morphological changes of cels were observed under an inverted microscope. Alkaline phosphatase (ALP) activity assay was performed by PNPP method. The mineralization nodules were observed and stained with alizarin red S and the number and area fraction were recorded under an inverted microscope. The mRNA expressions of osteogenesis-related genes ALP, Runx2, and osteocalcin were evaluated by quantitative real-time PCR (qRT-PCR). qRT-PCR and western blot were used to determine the expression level of β-catenin. The downstream β-catenin/TCF transcriptional activity was evaluated with the Dual-Luciferase Reporter Assay System.
RESULTS AND CONCLUSION: Compared with the control group, polygonatum sibiricum polysaccharide significantly enhanced the alkaline phosphatase activity, the mineralization ability of cels, and the mRNA expression of ALP, Runx2 and osteocalcin in the differentiated BMSCs in a dose dependent manner (P <0.05). After induction, the mRNA expression of β-catenin was the highest on the 3rd day. Polygonatum sibiricum polysaccharide significantly increased the expression of β-catenin (P < 0.05) in the process of promoting the differentiation of BMSCs into osteoblasts, and also promoted the high-level expression of luciferase reporter gene (TOPFlash) which contains wild type TCF binding sites (P < 0.05). These results demonstrate that Polygonatum sibiricum polysaccharide can promote the osteoblast differentiation of mouse BMSCs by activating the Wnt/β-catenin signaling pathway.