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ObjectivesTo investigate the value of contrast-enhanced computer tomography (CT)-based on radiomics in discriminating high-grade and low-grade hepatocellular carcinoma (HCC) before surgery.MethodsThe retrospective study including 161 consecutive subjects with HCC which was approved by the institutional review board, and the patients were divided into a training group (n = 112) and test group (n = 49) from January 2013 to January 2018. The least absolute shrinkage and selection operator (LASSO) was used to select the most valuable features to build a support vector machine (SVM) model. The performance of the predictive model was evaluated using the area under the curve (AUC), accuracy, sensitivity, and specificity.ResultsThe SVM model showed an acceptable ability to differentiate high-grade from low-grade HCC, with an AUC of 0.904 in the training dataset and 0.937 in the test dataset, accuracy (92.2% versus 95.7%), sensitivity(82.5% versus 88.0%), and specificity (92.7% versus 95.8%), respectively.ConclusionThe machine learning-based radiomics reflects a better evaluating performance in differentiating HCC between low-grade and high-grade, which may contribute to personalized treatment.

Background Large scale randomized trials have demonstrated that bevacizumab in addition to chemotherapy as first-line or second-line treatment has significant survival benefits. We aim to explore the clinical impact of bevacizumab in combination with chemotherapy in first-line or second-line in patients with colorectal cancer (CRC). Methods The medical records of patients with CRC who received bevacizumab at first or second-line of treatment were collected retrospectively. The primary outcome of the study was to evaluate the efficacy of bevacizumab in combination with chemotherapy by survival endpoints i.e. overall survival (OS) and progression-free survival (PFS) and the secondary outcome was to evaluate its safety by incidence of adverse events (AE). Results Fifty-one patients with CRC had met the selection criteria for treatment with bevacizumab to either cetuximab or FOLFOX or both. The median age was 54 years. During follow-up, ten patients had exhibited progression after treatment while 5 patients died. The median OS and PFS of the overall population were not reached. The Cox proportional regression analysis revealed no significant prognostic factors of OS and PFS for treatment with bevacizumab in various demographic subgroups. The 1-year PFS rates of all 51 patients was 76%. The 1-year and 3-year OS rates for all 51 patients were 95% and 88%, respectively. Toxicities were usually mild in nature, with nausea, vomiting, hand and foot syndrome, neutropenia, asthenia and palpitation being the commonly reported adverse events. Conclusion In this real-world setting, the efficacy and safety of bevacizumab in combination with chemotherapy is limited and further research is warranted as to whether bevacizumab with chemotherapy is an optimal treatment as first-line or second-line therapy in Chinese CRC patients.

Previous researches have found that chronic neck pain was closely related to depression. However, the relation between chronic neck pain, sleep quality, exercise and depression remains unclear. This study aims to evaluate the association between these factors, based on the assumption that sleep quality and exercise are potential mediators in the relationship between chronic neck pain and depression. This cross-sectional study enrolled 231 patients with chronic neck pain who were referred to outpatient clinics in department of neurology between July and December 2016. Data analysis was performed using a structural equation model to evaluate the mediating effects of sleep quality and exercise frequency on the relation between chronic neck pain intensity and depression. A positive correlation between neck pain intensity and depression was unveiled. In addition, sleep quality was identified as a significant positive mediator between neck pain intensity and depression, and exercise can help relieve depression. Poor sleep quality leads to an increase of the symptoms of depression for people with high neck pain intensity which can be effectively relieved via additional exercise.

Metformin had exerted important inhibitory effects in multiple cancers. However, the correlation between metformin and hepatocellular carcinoma (HCC) metastasis, and the relevant mechanisms are still unclear. By quantitative proteomics analysis technique, we found metformin could suppress FGF signalling significantly. In FGF signalling basic fibroblast growth factor (bFGF) is a crucial member, it initially binds to its receptors, the complex of bFGF and receptors activate FGF signallings, and promote many cancers progressions. When treating HCC cell lines HepG2 and Huh7 with bFGF, we observed the cells exhibited epithelial mesenchymal transition (EMT) and these cells metastasis potential was enhanced dramaticlly. However, when treating with metformin and bFGF together, EMT and metastasis induced by bFGF could be inhibited in these cells. Furthermore, bFGF could activate AKT/GSK-3β signalling, sequentially decrease the interaction between GSK-3β and Twist1 and decrease ubiquitination of Twist1 leading to Twist1 degradation reducing. While metformin could repress the bFGF-mediated activation in AKT/GSK-3β signalling, inhibition on interaction between GSK-3β and Twist1, enhancement of Twist1 stability. Taken together, our findings suggested that metformin had prominent negative effects on bFGF-induced EMT and metastasis in HCC cells.

Autophagy plays an essential role in cellular homeostasis in kidney. Previous studies have found that aristolochic acid (AA) can induce autophagy of renal tubular epithelial cells and epithelial-to-myofibroblast transition (EMT). However, the relationship between AA-induced autophagy and EMT is unclear. Our results showed that, after AA stimulation, the appearance of autophagy preceded EMT. Autophagy of HKC cells began to increase gradually from the 3rd hour, reached the peak at 12th hour, and then weakened gradually until 36th hour; the EMT process of HKC continued to increase from 6th hour to 36th hour after AA stimulation. The enhancement of autophagy using autophagy inducers, rapamycin or serum-free medium, led to an aggravation of EMT and upregulated expression of fibronectin, a component of extracellular matrix, in AA-treated HKC cells. In contrast, the inhibition of autophagy by autophagy inhibitor, 3-methyladenine, or by knockdown of Beclin 1 led to an attenuation of EMT and downregulated expression of fibronectin in AA-treated HKC cells. Taken together, our study suggests that, after AA stimulation, two types of cell responses of HKC cells, autophagy and EMT, will successively appear, and autophagy can promote EMT of HKC.

Podocyte injury critically contributes to the pathogenesis of obesity-related glomerulopathy (ORG). Recently, lipid accumulation and inflammatory responses have been found to be involved in podocyte injury. This study is to explore their role and relationship in podocyte injury of ORG. In animal experiments, the ORG mice developed proteinuria, podocyte injury, and hypertriglyceridemia, accompanied with deregulated lipid metabolism, renal ectopic lipid deposition, activation of NOD-like receptor protein 3 (NLRP3) inflammasome, and secretion of IL-1

Podocyte injury critically contributes to the pathogenesis of obesity-related glomerulopathy (ORG). Recently, lipid accumulation and inflammatory responses have been found to be involved in podocyte injury. This study is to explore their role and relationship in podocyte injury of ORG. In animal experiments, the ORG mice developed proteinuria, podocyte injury, and hypertriglyceridemia, accompanied with deregulated lipid metabolism, renal ectopic lipid deposition, activation of NOD-like receptor protein 3 (NLRP3) inflammasome, and secretion of IL-1β of the kidney. The expression of adipose differentiation-related protein (ADRP), CD36, sterol regulatory element-binding protein 1 (SREBP-1), and peroxisome proliferator-activated receptor α (PPARα) in renal tissue were increased. In in vitro cell experiments, after cultured podocytes were stimulated with leptin, similar to ORG mice, we found aggravated podocyte injury, formatted lipid droplet, increased expression of ADRP and CD36, activated NLRP3 inflammasome, and released IL-1β. In addition, after blocking CD36 with inhibitor sulfo-N-succinimidyl oleate (SSO) or CD36 siRNA, activation of NLRP3 inflammasome and release of IL-1β are downregulated, and podocyte injury was alleviated. However, after blocking NLRP3 with MCC950, although podocyte injury was alleviated and release of IL-1β was decreased, there was no change in the expression of CD36, ADRP, and intracellular lipid droplets. Taken together, our study suggests that CD36-mediated lipid accumulation and activation of NLRP3 inflammasome may be one of the potential pathogeneses of ORG podocyte injury.

Obesity-related glomerulopathy (ORG) is morphologically characterized by glomerulomegaly with or without observable focal segmental glomerulosclerosis under light microscope, with decreased podocyte density and number, and with increased foot‑process width observed under electron microscope. The severity of podocyte injury is correlated with the degree of proteinuria and renal dysfunction. However, the pathogenesis of ORG is not well understood. The aim of the present study was to explore the possible pathogenic role of aldosterone (ALDO) in ORG. In the in vivo animal experiments, body weight, Lee's obesity index, abdominal fat index, urinary protein excretion, average glomerular diameter were significantly increased, the mRNA and protein expression of podocyte‑associated molecules including nephrin, podocin, podoplanin and podocalyxin were significantly reduced, and the Wnt/β‑catenin signaling pathway was activated in ORG model mice compared with the Control mice, whereas the administration of spironolactone significantly ameliorated these effects. In the in vitro experiments on cultured podocytes, the mRNA and protein expression levels of the aforementioned podocyte‑associated molecules were significantly downregulated and the Wnt/β‑catenin signaling pathway was activated following ALDO stimulation, whereas eplerenone significantly attenuated all the above effects. Dickkopf‑related protein 1 (DKK1), an inhibitor of Wnt/β‑catenin signaling pathway, also reduced the effects of ALDO exposure on the expression of podocyte‑associated molecules. The present study hypothesized that ALDO may be involved in the pathogenesis of ORG through the activation of Wnt/β‑catenin signaling pathway in podocytes.

Background/Aims. It is known that chronic low-grade inflammation contributes to the initiation and development of both diabetes and diabetic nephropathy (DN), so we designed this study to investigate the role of P2X7R and NLRP3 inflammasome in DN pathogenesis and the antagonistic effects of artificially cultivated Ophiocordyceps sinensis (ACOS). Methods. A rat model of DN caused by high-fat-diet feeding and low-dose streptozotocin injection and a mouse podocyte injury model induced by high-glucose (HG) stimulation were established, and the intervention effects of ACOS on them were observed. The biological parameters of serum and urine and the pathological manifestations of kidney tissue were examined. The expression of mRNA and protein of P2X7R and NLRP3 inflammasome (NLRP3, ASC, and caspase-1) and downstream effectors (IL-1β and IL-18), as well as podocyte-associated molecules, was determined by real-time quantitative PCR and Western blot assay, respectively. Results. The DN rats showed to have developed insulin resistance, elevated fasting blood glucose, increased urinary protein excretion, and serum creatinine level as well as corresponding glomerular pathological alterations including podocyte damages. ACOS significantly antagonized the above changes. The experiments in vivo and in vitro both displayed that the mRNA and protein expression of P2X7R, NLRP3, ASC, caspase1 (procaspase-1 mRNA in the gene level and active caspase-1 subunit P10 in the protein level), IL-1β, and IL-18 was significantly upregulated and the mRNA and protein expression of podocyte-associated molecules was significantly changed (downregulation of nephrin, podocin, and WT-1 expression and upregulation of desmin expression) indicating podocyte injury in the kidney tissue of DN rats and in the HG-stressed mouse podocytes, respectively. ACOS also significantly antagonized all the above changes. Conclusion. Our research work suggests that P2X7R and NLRP3 inflammasome are involved in the pathogenesis of DN, and ACOS can effectively inhibit the high expression of P2X7R and the activation of NLRP3 inflammasome, which may contribute to the therapeutic effects of Ophiocordyceps sinensis.

Background and objective: The fact that mineralocorticoid receptor antagonists reduce structural and functional alterations induced by cyclosporine A (CsA) indicates that aldosterone plays a key role in chronic CsA nephrotoxicity. We and other researchers have reported local renal aldosterone synthesis. To investigate local renal aldosterone’s role in chronic CsA nephrotoxicity, we evaluated the effect of eplerenone (Epl) on renal structural damage and renal dysfunction in adrenalectomized (ADX) rats, and assessed whether the therapeutic benefit was associated with reduction of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), plasminogen activator inhibitor type 1 (PAI-1) and collagen I (COL-I) expression. Methods: Male Sprague-Dawley rats fed a normal-sodium diet were divided in four groups: sham-ADX, ADX, CsA, or Epl. Rats in the ADX, CsA and Epl groups were adrenalectomized first. Aldosterone, sodium and potassium levels in serum and urine were measured on the second day. Two weeks later, vehicle (sham-ADX and ADX group), CsA (25mg/kg/d), or CsA and Epl (100 mg/ kg/d) combination was administrated, respectively. After six weeks, urinary protein, creatinine clearance (C cr ), tubulointerstitial fibrosis (TIF), aldosterone level in kidney, and renal aldosterone synthase CYP11B2, COL-I, TGF-β1, CTGF and PAI-1 gene expression levels were determined. Results: On the second day after surgery, adrenalectomized rats showed undetectable aldosterone with natriuresis, hyponatremia, decreased urinary potassium excretion and hyperpotassemia. CsA reduced C cr , induced urinary proteins and up-regulated COL-I, TGF-β1, CTGF and PAI-1 gene expression with a significant development of TIF. Eplerenone administration prevented TIF and COL-I, TGF-β1 and PAI-1 up-regulation but did not improve renal function. Conclusion: Our results suggest local renal aldosterone is an important mediator of renal injury induced by CsA.

Rationale IgG4-related disease (IgG4-RD) is a systemic autoimmune disease and mixed cryoglobulinemia may be caused by autoimmune diseases. However, so far only 1 case of IgG4-RD complicated with mixed cryoglobulinemia is reported. Our case further confirms the close relationship between these 2 diseases. Patient concerns A 55-year-old female was admitted because of dry mouth and teeth falling off. Diagnoses The patient was diagnosed as IgG4-related sialadenitis (IgG4-RS) complicated with type III mixed cryoglobulinemia. IgG4-RS was confirmed by elevated serum IgG4 levels and diffuse IgG4 plasmocyte infiltration and storiform fibrosis in the interstitium of labial gland. Type III mixed cryoglobulinemia was confirmed by positive serum cryoglobulins and no monoclonal immunoglobulin in serum and urine. Interventions and outcomes After treatment with prednisone and cyclophosphamide, serum cryoglobulins rapidly turned negative with the remission of IgG4-RS. Lessons Type III mixed cryoglobulinemia can be caused by IgG4-RS, and the underlying mechanisms need to be further explored.

Radix Tetrastigma Hemsleyani Flavone (RTHF) is widely used as a traditional herb for its detoxification and anti-inflammation activity. Recently, several studies have shown that RTHF can inhibit growth and induce apoptosis in human cancer cell lines. However, the mechanisms are not completely understood yet. In this study we investigated the potential effects of RTHF on growth and apoptosis in human lung adenocarcinoma A549 cells as well as its mechanisms. A549 cells were treated with RTHF at various concentrations for different times. In vitro the MTT assay showed that RTHF had obvious anti-proliferation effects on A549 cells in a dose- and time- dependent manner. Cell morphological changes observed by inverted microscope and Hoechst33258 methods were compared with apoptotic changes observed by fluorescence microscope. Cell apoptosis inspected by flow cytometry showed significant increase in the treatment group over the control group (P0.01). Expression of apoptosis related Bax/Bcl-2, caspases and MAPK pathway proteins were detected by Western blotting. The results showed that RTHF up-regulated the Bax/Bcl-2 ratio and cle-caspase3/9, cle-PARP expression in a dose- dependent manner. Expression of p-p38 increased, p-ERK decreased significantly and that of p-JNK was little changed in the RTHF group when compared with the control group. These results suggest that RTHF might exert anti-growth and apoptosis activity against lung cancer A549 cells through activation of caspases and Bcl-2 family proteins and the MAPK pathway, therefore presenting as a promising therapeutic agent for the treatment of lung cancer.

Results of the relationships between dietary whole-grain consumption and the risk of all-cause, CVD and cancer-specific mortality are mixed. We summarised the evidence based on a meta-analysis of prospective cohort studies. Pertinent studies were identified by searching articles in the MEDLINE and EMBASE databases up to 20 January 2016 and by reviewing the reference lists of the retrieved articles. Random-effects models were used to calculate summary relative risks (SRR) and 95 % CI. In all, eleven prospective studies (ten publications) were included in the meta-analysis. There were a total of 816 599 subjects and 89 251 cases of all-cause mortality. On the basis of the highest v. the lowest categories of intake, whole grains may be associated with a lower risk of mortality from all causes (SRR 0·87; 95 % CI 0·84, 0·90), CVD (SRR 0·81; 95 % CI 0·75, 0·89) and all cancers (SRR 0·89; 95 % CI 0·82, 0·96). For each 3 servings/d increase in whole-grain intake, there was a 19 % reduction in the risk of all-cause mortality (SRR 0·81; 95 % CI 0·76, 0·85), a 26 % reduction in CVD mortality (SRR 0·74; 95 % CI 0·66, 0·83) and a 9 % reduction in cancer mortality (SRR 0·91; 95 % CI 0·84, 0·98). The current meta-analysis provides some evidence that high intake of whole grains was inversely associated with the risk of all-cause, CVD and cancer-specific mortality. Further well-designed studies, including clinical trials and in different populations, are required to confirm our findings.

The objectives of this study are to explore whether separate sources of trans fatty acids (TFA) have different effects on ECV304 cell line and to further elucidate the oxidation mechanism induced by TFA. ECV304 cells are used in the study because they display many endothelial features. Cell apoptosis rates increased in a dose-dependent manner following 24-h treatment with TFA from separate sources. Additionally, TFA stimulated human alpha-defensin 1 (HNP-1) expression and resulted in a significant increase in both malondialdehyde (MDA) and ROS levels. MDA levels reach their peak at 18 h. HNP-1 expression levels increase at 2 h and then reach their peak at 10 h. At the same time, the protein carbonyl (PCO) value declines slightly. After 10 h of TFA co-culture, the cells were washed and fresh low-density lipoprotein (LDL) was added. MDA generation significantly increased after 6 h and it could be inhibited by 4-aminobenzoic acid hydrazide (ABAH) or sodium ferulate. However, after the TFA co-culture for 2 h, adding LDL for 6 h just caused slight MDA generation change and the MDA generation could be inhibited by verapamil or sodium ferulate. TFA from different sources did not have different effects on ECV304. HNP-1 mediates the oxidation induced by TFA by activating ROS. Furthermore, TFA can stimulate the oxidation of LDL in ECV304 cells through both passive and active pathway. In the oxidation induced by linoelaidic acid, ABAH can decrease the MDA generation in active oxidation pathway and verapamil can decrease the MDA generation in passive oxidation pathway.

The present study investigated the effects of curcumin, one of the most important active ingredients of turmeric, on podocyte injuryin vitroand obesity-related glomerulopathy (ORG)in vivo. Cellular experimentsin vitroshowed that curcumin significantly antagonized leptin-induced downregulation of the mRNA and protein expression of podocyte-associated molecules including nephrin, podocin, podoplanin, and podocalyxin. Animal experimentsin vivoshowed that curcumin significantly reduced the body weight, Lee’s index, abdominal fat index, urinary protein excretion, and average glomerular diameter and significantly upregulated the mRNA and protein expressions of the above podocyte-associated molecules in ORG mice. Furthermore, the experimentsin vitroandin vivoboth displayed that curcumin could downregulate the mRNA and protein expressions of Wnt1, Wnt2b, Wnt6, andβ-catenin and upregulate the phosphorylation level ofβ-catenin protein in podocytes and renal tissue. In conclusion, curcumin is able to alleviate the harmful reaction of leptin on podocytes and reduce the severity of ORG. The above protective effects are associated with the inhibition of Wnt/β-catenin signaling activation in podocytes.

Finite element analysis plays an important role in dental implant design. The objective of this study was to show the effect of the overall geometry of dental implants on their biomechanics after implantation. In this study, 12 dental implants, with the same length, diameter and screw design, were simulated from different implant systems. Numerical model of right mandibular incisor bone segment was generated from CT data. The von-Mises stress distributions and the total deformation distributions under vertical/lateral load were compared for each implant by scores ranking method. The implants with cylindrical shapes had highest scores. Results indicated that cylindrical shape represented better geometry over taper implant. This study is helpful in choosing the optimal dental implant for clinical application and also contributes to individual implant design. Our study could also provide reference for choice and modification of dental implant in any other insertion sites and bone qualities.

Although ectopic expression of the cholecystokinin B/gastrin receptor (CCK-BR) is widely reported in human colorectal cancers, its role in mediating the proliferative effects of gastrin1-17 (G-17) on these cancers is unknown. Here we report the isolation of a novel splice variant of CCK-BR that exhibits constitutive (ligand-independent) activation of pathways regulating intracellular free Ca(2+) ([Ca(2+)](i)) and cell growth. The splice variant (designated CCK-BRi4sv for intron 4-containing splice variant) is expressed in colorectal cancers but not in normal colonic mucosa adjacent to the cancer. Balb3T3 cells expressing CCK-BRi4sv exhibited spontaneous, ligand-independent, oscillatory increases in [Ca(2+)](i), whereas cells expressing wild-type CCK-BR did not. Primary cultures of cells isolated from resected colorectal cancers also exhibited a similar pattern of spontaneous [Ca(2+)](i) oscillations. For both Balb3T3 and primary tumor cells, application of G-17 (10 and 200 nm, respectively) caused an increase in [Ca(2+)](i). Selective CCK-BR antagonists blocked the G-17-stimulated Ca(2+) responses but not the spontaneous [Ca(2+)](i) oscillations. Cells expressing CCK-BRi4sv exhibited an increased growth rate ( approximately 2.5-fold), in the absence of G-17, compared with cells expressing wild-type CCK-BR. The selective pattern of expression, constitutive activity, and trophic action associated with CCK-BRi4sv suggest that this variant may regulate colorectal cancer cell proliferation though a gastrin-independent mechanism.

Aim The aim of this study was to evaluate the finite element analysis (FEA) approach to assess biomechanical performance of individual endoprostheses used in the reconstruction of extensive mandibular defects, and to explore an available strategy for the optimal design of prostheses. Material and methods A female patient experienced fracture of a titanium mandibular endoprosthesis one year after reconstructive surgery. The endoprosthesis was placed during resection of a mandibular carcinoma. Using CT data, a finite element analysis (FEA) of the implant was performed to identify potential causes for this mechanical failure. Based on the first FEA analysis, modifications of the prosthesis geometry and screw configuration were carried out. FEA was performed for each subsequent modification until no stress concentration areas were identified. The final version of the titanium prosthesis was implanted during the second mandibular reconstruction. Results The FEA model was constructed, based on the geometrical data of the patient. Two areas of stress concentration were identified in the original prosthesis: - at the top surface of the left stem, 1.5 cm away from the corner (the peak stress was 616 MPa) and - on the exterior surface of the right stem, close to the mandibular stump margin. The mechanical failure occurred at the top surface of the left stem. Some common characteristics of the biomechanical performance were noted in the two models, but lower overall stress was achieved in the second, optimized prosthesis. By thickening the recognized high stress areas, and attenuating those areas subject to less stress, then adopting a quadrilateral screw configuration, this dispersed the stress more evenly in the optimized endoprosthesis. Function in the optimized reconstructed mandible was observed for 3 years without significant endoprosthesis related complication. Conclusion In some patients with extensive mandibular defects, the individually tailored endoprosthesis constructed with regard to minimizing stress concentration using this method seems to have a place. The prosthesis geometry and screw configuration influence the stress–strain distribution on the reconstructed mandible. Our FEA approach can optimize the design of individual endoprostheses and give the reconstructed mandible improved biomechanical performance.

Background Folate, one of the B vitamins, provides the one-carbon units required for methylation. Folate deficiency has been associated with many pathologies. However, much less is known about the effect of it on human reproduction, especially on implantation. The establishment of uterine receptivity is crucial for successful embryo implantation. Gene expression can be influenced by both heredity and epigenetics such as DNA methylation. However, it is not known whether the methylation and expression of genes related to uterine receptivity can be affected by folate levels. To explore whether folate deficiency affected the epigenetic regulation of genes related to uterine receptivity, and their influence on implantation, we investigated the methylation and expression of cadherin 1 (Cdh1), progesterone receptor (Pgr) and estrogen receptor 1 (Esr1) genes during implantation and the implantation efficiency using a folate-deficient pregnant mouse model. Methods Serum folate levels of pregnant mice were measured using the electro-chemiluminescence immunoassay. The methylation status of Cdh1, Pgr and Esr1 promoter regions was determined by methylation-specific PCR and bisulfite sequencing. The expression of Cdh1, Pgr and Esr1 in the implantation-site endometrium was examined by real-time PCR, western blot and immunohistochemistry. The number and the morphology of pinopodes, important morphological markers of endometrial receptivity, were examined using scanning electron microscopy. The number of implantation sites demarcated by distinct blue bands was recorded. Results Serum folate levels of the folate-deficient group were lower (5.42 ± 1.35 ng/ml, n= 42) than those of the normal group (24.13 ± 4 .26 ng/ml, n= 37; P = 0.003). Here we show that the methylation status and mRNA levels of Esr1 were decreased (P= 0.021, P= 0.045, respectively), while the Cdh1 and Pgr expression levels were slightly but not significantly elevated and the methylation status did not vary in the folate-deficient mice compared with the wild type. Neither the number nor morphology of pinopodes was affected by folate deficiency. Furthermore, folate deficiency did not affect the number of implantation sites in mice. Conclusions This study demonstrates for the first time that, unlike the effects on Esr1, folate deficiency in mice does not influence the methylation and expression of Pgr and Cdh1, two genes shown to be essential for uterine receptivity and embryo implantation. Embryo implantation in mice appears to be unaffected by a deficiency in folate, suggesting that abnormalities in a pregnancy caused by folate deficiency start to develop after implantation.

Statement of problem A variety of zygomatic implantation techniques currently exist; however, a consensus regarding the most suitable method has not yet been reached. Purpose The purpose of this study was to evaluate and compare 3 zygomatic implantation techniques and to clarify the optimal number and position of zygomatic and dental implants for the reconstruction of the severely atrophied edentulous maxilla. Material and methods A 3-dimensional finite element analysis craniofacial model was constructed from the computed tomography data of a selected patient with a severely atrophic edentulous maxilla. Modeled zygomatic implants were inserted into the craniofacial model with 3 surgical techniques (classic Branemark, exteriorized, and extramaxillary), and with 3 model variations that involved the number and position of zygomatic and dental implants. The zygomatic implants were loaded with a vertical force of 150 N and a lateral force of 50 N. The stresses on and deformations of the bones and implants were then observed and compared. Results No obvious differences in the amount and distribution of stress on the external craniofacial bones were detected in the models. The lowest stresses on the zygomatic implants were observed in the exteriorized technique group. The lowest deformations of the bone that surrounds zygomatic implants and dental implants were observed in the exteriorized technique and classic Branemark technique groups. For the exteriorized technique group, the model with 1 dental implant in the site of the maxillary lateral incisor exhibited the lowest stress on the zygomatic implants and the least deformation of the bone surrounding the zygomatic and dental implants. Conclusions All 3 zygomatic implant techniques resulted in more or less homogeneous transference of force and thus could reconstruct the edentulous maxilla; however, the exteriorized technique with 1 dental implant in the lateral incisor appeared to be the most appropriate reconstruction method for the severely atrophied edentulous maxilla.

BACKGROUND: The DNA demethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR) incorporates into DNA and decreases DNA methylation, sparking interest in its use as a potential therapeutic agent. We aimed to determine the effects of maternal 5-aza-CdR treatment on embryo implantation in the mouse and to evaluate whether these effects are associated with decreased levels of DNA methyltransferases (Dnmts) and three genes (estrogen receptor α [Esr1], progesterone receptor [Pgr], and homeobox A10 [Hoxa10]) that are vital for control of endometrial changes during implantation. METHODS AND PRINCIPAL FINDINGS: Mice treated with 5-aza-CdR had a dose-dependent decrease in number of implantation sites, with defected endometrial decidualization and stromal cell proliferation. Western blot analysis on pseudo-pregnant day 3 (PD3) showed that 0.1 mg/kg 5-aza-CdR significantly repressed Dnmt3a protein level, and 0.5 mg/kg 5-aza-CdR significantly repressed Dnmt1, Dnmt3a, and Dnmt3b protein levels in the endometrium. On PD5, mice showed significantly decreased Dnmt3a protein level with 0.1 mg/kg 5-aza-CdR, and significantly decreased Dnmt1 and Dnmt3a with 0.5 mg/kg 5-aza-CdR. Immunohistochemical staining showed that 5-aza-CdR repressed DNMT expression in a cell type-specific fashion within the uterus, including decreased expression of Dnmt1 in luminal and/or glandular epithelium and of Dnmt3a and Dnmt3b in stroma. Furthermore, the 5' flanking regions of the Esr1, Pgr, and Hoxa10 were hypomethylated on PD5. Interestingly, the higher (0.5 mg/kg) dose of 5-aza-CdR decreased protein expression of Esr1, Pgr, and Hoxa10 in the endometrium on PD5 in both methylation-dependent and methylation-independent manners. CONCLUSIONS: The effects of 5-aza-CdR on embryo implantation in mice were associated with altered expression of endometrial Dnmts and genes controlling endometrial changes, suggesting that altered gene methylation, and not cytotoxicity alone, contributes to implantation defects induced by 5-aza-CdR.

Negative ions technology has been widely used to deal with air pollution problems in recent years. In this paper, a negative ions generating circuit is designed for dealing with the exhaust gas from vehicles. In the high electric field, the air is ionized. The number of active particles increases in the air. These particles react with the exhaust gas, and clean the air. The circuit analysis and simulation are presented in this paper.

A 39-year-old woman with end-stage renal disease due to chronic glomerulonephritis had been undergoing regular hemodialysis for 18 years. She was noncompliant with diet and did not take any phosphate binders or vitamin D. Thirteen years ago she began to develop facial deformity, which was progressive (Figure 1). This was accompanied by a 14-cm shortening of her height, kyphoscoliosis, and an inability to walk because of severe leg pain. The level of serum intact parathyroid hormone was 42000 pg/ml, and serum calcium, phosphate, and alkaline phosphatase were 9.3, 6.7 mg per 100 ml, and 1180 IU/l, respectively. The ultrasonography showed four hyperplastic parathyroid glands with rich blood supply. Skull X-ray showed thickening of bone plates of skull and multiple areas of osteolysis, leading to a change in the shape of the bones of facial cranium with enlarged jaw, blunting of the angle of mandible, and disappearance of the lamina dura of alveolar bone (Figure 1). Total parathyroidectomy was successfully carried out with subsequent reduction of intact parathyroid hormone to 100 pg/ml, and improvement of the serum levels of calcium, phosphate, and alkaline phosphatase. Her general and nutrition state improved with the stabilization of her body height and improvement of leg pain. Her facial deformation also improved with corresponding improvement in her skull X-ray (Figure 2). Uremic leontiasis is a rare form of renal osteodystrophy associated with massive thickening of the cranial vault and facial bones. n e p h r o l o g y i m a g e http://www.kidney-international.org