Risk Factors of Contrast Agent Intravasation With Sulfur Hexafluoride Microbubble During Hysterosalpingo-Contrast Sonography.

OBJECTIVES: To analyze the risk factors of sulfur hexafluoride microbubble contrast agent intravasation during hysterosalpingo-contrast sonography (HyCoSy), and to explore a simple prediction model by the obvious clinical history. METHODS: This was a retrospective study included 299 infertility women who had undergone HyCoSy examination from July 1, 2018 to June 31, 2019. The factors were recorded, including age, endometrial thickness, balloon length, infertility type, history of intrauterine surgery, history of pelvic surgery, and tubal patency. The method of multivariate logistic regression analysis was adopted to analyze the risk factors affecting the contrast agent intravasation, and the receiver operating characteristic curves were plotted to test their efficacy. RESULTS: Secondary infertility, a history of intrauterine surgery, thin endometrial thickness, and tubal obstruction were all risk factors of the occurrence of intravasation (P < .05). And the area under the receiver operating characteristic curves of the multifactor-combined prediction model of the intravasation was significantly larger than that of single-factor. CONCLUSIONS: Sonographers and gynecologists should be familiar with the risk factors of intravasation and select the appropriate timing of HyCoSy toward reducing the occurrence of intravasation and other complications after thoroughly explaining and communicating with the patients.

Localized Recrystallization of a Lithium-Metal Anode during Fast Stripping in High-Activity Liquid Electrolytes.

The lithium-metal anode is one of the most promising candidates for "beyond-lithium-ion" batteries thanks to its high specific capacity and low negative electrochemical potential. However, the electrode-electrolyte interface instability hinders its commercialization in rechargeable batteries. During cycles of charging and discharging, the lithium-metal anode is electrochemically plated and stripped along with the morphological evolution, which determines the cycling performance. In this work, with a phase-field model, we computationally characterize the morphological evolution dynamics during the plating and stripping steps at the lithium-metal-electrolyte interface. Our model is valid in a wide range of lithium concentrations in liquid electrolytes by incorporating nonidealities of electrolyte solutions into the interfacial reaction kinetics. Intriguingly, at fast stripping, i.e., high discharging overpotential, we observe an unexpected localized recrystallization phenomenon in high-lithium-ion-concentration valley regions. This recrystallization phenomenon mitigates the overall reaction rate heterogeneity and provides a potential approach to improving the morphological stability. Furthermore, we systematically investigate the correlation between the recrystallization phenomenon and lithium-ion activity and draw a simplified phase diagram for the overpotential-dependent recrystallization.

Operator's Influence on Contrast Agent Intravasation During Hysterosalpingo-Contrast Sonography: Explanation Based on a Physics Model.

Objective: To analyze the risk factors of the operators on contrast agent intravasation during hysterosalpingo-contrast sonography (HyCoSy). Methods: We retrospectively collected 399 infertile women who underwent HyCoSy by the same sonographer. These patients were divided into two groups according to the way how the assistants connected the syringe to the uterus radiography catheter to inject the contrast agent. We analyzed whether the use of different contrast bolus injection methods had any influence on the incidence of intravasation during HyCoSy. Results: There was no significant difference between the two groups with different cross-sectional areas of the syringe outflow tract in the risk variables for intravasation, but the intravasation rates of the two groups were different, 26.4% in group A and 17.1% in group B, P <0.05. The primary manifestation was that when both fallopian tubes were unobstructed, the intravasation rate of group B with smaller cross-sectional area of the outflow tract of the syringe was lower, and the difference was statistically significant. The inferences drawn from our physics model were also in line with the clinical results. Conclusion: The influence of different operators on the contrast agent intravasation rate of HyCoSy cannot be ignored. The assistants of HyCoSy examination should inject the contrast agent slowly and steady, and a needle can be used as a flow restrictor to control the flow into the uterine cavity per unit time, slow down the rising speed of intrauterine pressure, and avoid the accumulation of contrast agent in the uterine cavity, so as to reduce the intravasation caused by operator factors.

Transcriptome analysis of the gills of Eriocheir sinensis provide novel insights into the molecular mechanisms of the pH stress response.

Eriocheir sinensis is an important economic species in China, which is easily affected by pH changes. However, the molecular mechanism of the pH stress response in E. sinensis is still unclear. Therefore, this study aimed to examine the molecular response mechanism of E. sinensis based on pH variation surveillance, histopathological evaluation and transcriptomic analyses. Firstly, pH variation surveillance showed that E. sinensis could actively regulate the pH of its environment. Meanwhile, the histopathological evaluation suggested that pH stress seriously damaged the gills, especially at high pH. Finally, transcriptome analysis showed that the expression of genes related to ion transport, immune stress, and energy metabolism significantly changed. Many genes played an important role in the pH response of E. sinensis, such as carbonic anhydrase (CA), mitochondrial proton/calcium exchanger protein (LETM1), recombinant sodium/hydrogen exchanger 3 (SLC9A3/NHE3), heat shock protein 90 alpha family class a member (HSP90A), alkylglycerone phosphate synthase (AGPS), succinate-CoA ligase ADP-forming subunit beta (LSC2), and superoxide dismutase (SOD). Our study revealed the molecular response mechanism of E. sinensis in response to pH stress, thus providing a basis for further research on the molecular mechanism of response to pH stress in aquatic animals.

A New Stemness-Related Prognostic Model for Predicting the Prognosis in Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: This study is aimed at identifying stemness-related genes in pancreatic ductal adenocarcinoma (PDAC). METHODS: The RNA-seq data of PADC patients were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The mRNA expression-based stemness index (mRNAsi) and epigenetically regulated mRNAsi (EREG-mRNAsi) of PADC patients were evaluated. The mRNAsi-related gene sets in PADC were identified by weighted gene coexpression network analysis (WGCNA). The key genes were further analyzed using functional enrichment analysis. The Kaplan-Meier survival analysis and the Cox proportional hazards model were used to evaluate the prognostic value of the key genes. Prognostic hub genes were used to establish nomograms. The receiver operating characteristic (ROC) curves, concordance index (C-index), and calibration curves were used to assess the discrimination and accuracy of the nomogram. Finally, these results were validated in the Gene Expression Omnibus (GEO) database. RESULTS: A total of 36 key genes related to mRNAsi were identified by WGCNA. A prognostic gene signature compromising seven genes (TPX2, ZWINT, UBE2C, CCNB2, CDK1, BUB1, and BIRC5) was established to predict the overall survival (OS) of PADC patients. The Cox regression analysis revealed that the risk score was an independent prognostic factor for PADC. Patients were then divided into the high-risk and low-risk groups. The ROC curves, C-index, and calibration curves indicated good performance of the prognostic signature in the TCGA and GEO datasets. Moreover, the nomogram incorporating clinical parameters showed better sensitivity and specificity for predicting the OS of PADC patients. CONCLUSION: The stemness-related prognostic model successfully predicted the OS of PADC patients and could be used for the treatment of PADC.

Half-Brain Delineation for Prediction of Radiation-Induced Temporal Lobe Injury in Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiotherapy.

PURPOSE: To investigate the role of half-brain delineation in the prediction of radiation-induced temporal lobe injury (TLI) in nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: A total of 220 NPC cases treated with IMRT and concurrent platinum-based chemotherapy were retrospectively analyzed. Dosimetric parameters of temporal lobes, half-brains, and brains included maximum dose (Dmax), doses covering certain volume (DV) from 0.03 to 20 cc and absolute volumes receiving specific dose (VD) from 40 to 80 Gy. Inter-structure variability was assessed by coefficients of variation (CV) and paired samples t-tests. Receiver operating characteristic curve (ROC) and Youden index were used for screening dosimetric parameters to predict TLI. Dose/volume response curve was calculated using the logistic dose/volume response model. RESULTS: CVs of brains, left/right half-brains, and left/right temporal lobes were 9.72%, 9.96%, 9.77%, 27.85%, and 28.34%, respectively. Each DV in temporal lobe was significantly smaller than that in half-brain (P < 0.001), and the reduction ranged from 3.10% to 45.98%. The area under the curve (AUC) of DV and VD showed an "increase-maximum-decline" behavior with a peak as the volume or dose increased. The maximal AUCs of DVs in brain, half-brain and temporal lobe were 0.808 (D2cc), 0.828 (D1.2cc) and 0.806 (D0.6cc), respectively, and the maximal AUCs of VDs were 0.818 (D75Gy), 0.834 (V72Gy) and 0.814 (V70Gy), respectively. The cutoffs of V70Gy (0.86 cc), V71Gy (0.72 cc), V72Gy (0.60 cc), and V73Gy (0.45 cc) in half-brain had better Youden index. TD5/5 and TD50/5 of D1.2cc were 58.7 and 80.0 Gy, respectively. The probability of TLI was higher than >13% when V72Gy>0 cc, and equal to 50% when V72Gy = 7.66 cc. CONCLUSION: Half-brain delineation is a convenient and stable method which could reduce contouring variation and could be used in NPC patients. D1.2cc and V72Gy of half-brain are feasible for TLI prediction model. The dose below 70 Gy may be relatively safe for half-brain. The cutoff points of V70-73Gy could be considered when the high dose is inevitable.

Effectiveness of contrast-enhanced ultrasound for detecting the staging and grading of bladder cancer: a systematic review and meta-analysis.

AIM: The study retrospectively analysed the accuracy of preoperative contrast-enhanced ultrasound (CEUS) in differenti-ating stage Ta-T1 or low-grade bladder cancer (BC) from stage T2 or high-grade bladder cancer. MATERIAL AND METHODS: We systematically searched the literature indexed in PubMed, Embase, and the Cochrane Library for original diagnostic articles of bladder cancer. The diagnostic accuracy of CEUS was compared with cystoscopy and/or transurethral resection of bladder tumors (TURBT). The bivariate logistic regression model was used for data pooling, couple forest plot, diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC). RESULTS: Five studies met the selection criteria; the overall number of reported bladder cancers patients were 436. The pooled-sensitivity (P-SEN), pooled-specificity (P-SPE), pooled-positive likelihood ratio (PLR+), pooled-negative likelihood ratio (PLR-), DOR, and area under the SROC curve were 94.0% (95%CI: 85%-98%), 90% (95%CI: 83%-95%), 9.5 (95%CI: 5.1-17.6), 0.06 (95%CI: 0.02-0.17), 147 (95%CI: 35-612) and 97% (95% CI: 95%-98%) respectively. CONCLUSION: CEUS reaches a high efficiency in discriminating Ta-T1 or low-grade bladder cancer from stage T2 or high-grade bladder cancer. It can be a promising method in patients to distinguish T staging and grading of bladder cancer because of its high sensitivity, specificity and diagnostic accuracy.

Long non-coding RNA SNHG1 regulates rheumatoid synovial invasion and proliferation by interaction with PTBP1.

Fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) present proliferative and aggressive cell phenotype. RA-FLSs are the essential effector cells that lead to symptoms like synovial inflammation and joint destruction. Currently, the cause of RA-FLSs involving in the pathological process of RA remains unknown. Accumulate researches have demonstrated that lncRNAs may play a critical role in regulating the biological behaviors of RA-FLSs, but the mechanism is still unclear. Here, we found that lncRNA small nucleolar RNA host gene 1 (SNHG1) is up-regulated in RA-FLSs compared with FLSs from trauma arthritis and osteoarthritis patients. The results suggest that SNHG1 in RA-FLSs helps to sustain the cellular functions of proliferation, migration and invasion. Furthermore, the regulation mechanism depends on the interaction between SNHG1 and polypyridine tract-binding protein 1 (PTBP1). This interaction influences PTBP1 expression that participates in the regulation of RA-FLSs biological behaviors. Our results suggest that up-regulated SNHG1 of RA-FLSs may contribute to synovial aggression and disease progression in RA and be favourable for RA treatment target RA-FLSs.

Contrast-enhanced ultrasound for the preoperative assessment of laryngeal carcinoma: a preliminary study.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is considered an attractive imaging technique to evaluate tumor microcirculation. However, the validity of CEUS for assessing laryngeal carcinoma is unclear. PURPOSE: To compare the performance of CEUS with conventional US and contrast-enhanced computed tomography (CECT) in the diagnosis and preoperative T-staging of laryngeal carcinoma. MATERIAL AND METHODS: Forty-one consecutive patients with laryngeal carcinoma underwent conventional high-frequency US, CEUS, and CECT before surgery. The CEUS characteristics of laryngeal carcinoma were recorded. The imaging findings of CEUS and conventional US were compared with CECT findings and the postoperative pathological examination. RESULTS: CEUS showed hyperenhancement in 38 cases and isoenhancement in three cases. Homogeneous distribution of contrast agent was found in 20 cases and heterogeneous distribution in 21 cases, of which 16 cases showed local perfusion defects. In the enhanced phase, rapid entry was observed in 37 cases, synchronous entry was observed in two cases, and slow entry was observed in two cases. Rapid exit was observed in 25 cases and slow exit was observed in 16 cases. The pretherapeutic T-staging accuracy was not significantly different between conventional US, CEUS, and CECT (P ≥ 0.500). A high sensitivity and specificity were achieved by CEUS in the evaluation of involvement of thyroid cartilage. CONCLUSION: Compared with conventional US and CECT, CEUS has a reliable initial T-staging accuracy and diagnostic properties for detecting laryngeal cartilage invasion.

Synthesis of 2,5-diaryloxazoles through rhodium-catalyzed annulation of triazoles and aldehydes.

An efficient synthesis of a variety of 2,5-diaryloxazole derivatives via a rhodium-catalyzed annulation of triazoles and aldehydes is achieved. Various oxazole derivatives could be obtained in good to excellent yields. A concise synthesis of antimycobaterial natural products balsoxin and texamine has been achieved using this method.

Identification of Potential Biomarkers and Biological Pathways in Juvenile Dermatomyositis Based on miRNA-mRNA Network.

OBJECTIVE: The aim of this study is to explore the potential pathogenesis of juvenile dermatomyositis by bioinformatics analysis of gene chips, which would screen the hub genes, identify potential biomarkers, and reveal the development mechanism of juvenile dermatomyositis. MATERIAL AND METHODS: We retrieved juvenile dermatomyositis's original expression microarray data of message RNAs (mRNAs) and microRNAs (miRNAs) from NCBI's Gene Expression Omnibus database (GEO, http://www.ncbi.nlm.nih.gov/geo/); through the R package of limma in Bioconductor, we can screen the differentially expressed miRNAs and mRNAs, and then we further analyzed the predicted target genes by the methods such as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and miRNA-mRNA regulatory network construction and protein-protein interaction (PPI) network using Cytoscape 3.6.1. RESULTS: Compared with normal juvenile skin tissues, 6 upregulated microRNAs and 5 downregulated microRNAs were identified from 166 downregulated microRNAs and 58 upregulated microRNAs in juvenile dermatomyositis tissues. The enrichment pathways of differentially expressed microRNAs include cell adhesion molecules (CAMs), autoimmune thyroid disease, Type I diabetes mellitus, antigen and presentation, viral myocardium, graft-versus-host disease, and Kaposi sarcoma-associated herpes virus infection. By screening of microRNA-messenger RNA regulatory network and construction of PPI network map, three target miRNAs were identified, namely, miR-193b, miR-199b-5p, and miR-665. CONCLUSION: We identified mir-193b, mir-199b-5p, and mir-6653 target miRNAs by exploring the miRNA-mRNA regulation network mechanism related to the pathogenesis of juvenile dermatomyositis, which will be of great significance for further study on the pathogenesis and targeted therapy of juvenile dermatomyositis.

Catalyst-free cyclization of anthranils and cyclic amines: one-step synthesis of rutaecarpine.

An efficient synthesis of a variety of quinazolinone derivatives via a direct cyclization reaction between commercially available anthranils and cyclic amines is described. The developed transformation proceeds with the merits of high step- and atom-efficiency, a broad substrate scope, and good to excellent yields, without additional catalysts, and offers a practical way for the preparation of rutaecarpine and its derivatives with structural diversity.

Sonographic Assessment of Oropharynx Movement During Deep Breathing.

To investigate the feasibility of ultrasonography in detecting the oropharynx movement during deep breathing and to quantitatively analyze oropharynx airway lumen changes during deep breathing. The motions of oropharynx were monitored, and sonographic measurements of airway lumen were obtained during deep breathing in 448 healthy volunteers. Adequate visualization of oropharynx movement was obtained on all healthy volunteers. The anterior-posterior (AP) diameters and AP/transverse (T) diameter ratios were greater at the end of deep inspiration than that at the end of deep expiration for each sex (p < 0.01). The anterior-posterior dimensional changes were greater than lateral airway dimensional changes each sex (p < 0.05). Ultrasonography could provide realistic impression of the process on the oropharynx movement during deep breathing and perform the quantitative analysis of the oropharynx airway lumen changes during deep breathing. The results were encouraging and supported the utility of ultrasonography in future studies.

miR-140-5p regulates T cell differentiation and attenuates experimental autoimmune encephalomyelitis by affecting CD4+T cell metabolism and DNA methylation.

We previously demonstrated that decreased expression of miR-140-5p was associated with the progression of multiple sclerosis (MS) and miR-140-5p targeted STAT1 and interfered with the expression of IFN-γ. However, the underlying mechanisms how miR-140-5p regulated the differentiation of encephalomyelitic CD4+T cell remained unclear. In this study, we analyzed the levels of miR-140-5p in a mouse model of experimental autoimmune encephalomyelitis (EAE). We also analyzed the outcomes in response to either over- or under-expression of miR-140-5p. We found that the expression of miR-140-5p was inversely related to the progression of EAE. With the remission of the disease, the expression of miR-140-5p was restored to levels comparable to the control. The expression of miR-140-5p was downregulated in the encephalomyelitic CD4+T cells whereas enhanced expression of miR-140-5p inhibited the development of T helper type 1 (Th1) cell and significantly attenuated EAE. MiR-140-5p also caused hypermethylation of STAT1 and demethylation of GATA3. Furthermore, we found that miR-140-5p enhanced mitochondrial glycolysis in CD4+T cells with simultaneous activation of ATP activity. By blockage of the respiratory electron transport chain with the inhibitors of complex I and III, the effect of miR-140-5p on Th1 differentiation was blocked, which suggested a role for mitochondrial respiratory pathway in miR-140-5p-mediated inhibition of Th1 differentiation. In summary, our results demonstrated that the expression of miR-140-5p was negatively correlated with the progression of EAE and that miR-140-5p regulated Th1 differentiation via DNA methylation and mitochondrial respiratory pathway.

Contrast-enhanced ultrasonography of nasopharyngeal carcinoma: enhancement patterns and quantitative parameters.

OBJECTIVE: The aim of this study was to investigate the characteristics of nasopharyngeal carcinoma (NPC) using contrast-enhanced ultrasonography (CEUS), including the enhancement patterns and the quantitative parameters. METHODS: Having been scanned using conventional ultrasonography (US) and CEUS, every case was confirmed to be NPC under endoscopic biopsy, and no case received any anti-tumor treatment before CEUS examinations. Tumor/node/metastasis stages were determined in accordance with 2002 AJCC 6th edition. Contrast enhancement patterns and quantitative parameters were observed. RESULTS: CEUS imaging of NPC showed that the tumor signal intensity enhanced early, rapidly, and remarkably, and decreased slowly later. The patterns of enhancement included spot/linear enhancement, peripheral enhancement, and mass enhancement, and two types of time intensity curves of NPC included type I and type II. There was a significant difference between peak intensity (PI) and T stage (P<0.05), whereas time-to-peak (TP) and slope did not show significant differences with T stage (P>0.05). CONCLUSION: CEUS is feasible to be applied to the nasopharynx region. The use of CEUS makes it possible to observe vascular permeability of NPC. Our results suggest that the quantitative parameter PI of nasopharyngeal carcinoma is significantly different from T stages. Thus, PI may serve as a potential noninvasive radiological prognostic indicator for NPC.

Sonic Hedgehog Signaling Pathway Mediates Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via MAPK/ERK Signaling Pathway.

Fibroblast-like synoviocytes (FLSs) are the major effector cells that lead to rheumatoid arthritis (RA) synovitis and joint destruction. Our previous studies showed that Sonic Hedgehog (SHH) signaling pathway is involved in aberrant activation of RA-FLSs and inhibition of SHH pathway decreases proliferation and migration of RA-FLSs. The objective of this study was to investigate if the SHH pathway mediates proliferation and migration of RA-FLSs via the mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK) signaling pathway. SHH signaling was studied by using SHH agonist (Purmorphamine) and antagonist (Cyclopamine) targeting the Smoothened (SMO) in FLSs. U0126-EtOH was used to inhibit the MAPK/ERK signaling pathway. The phosphorylation of ERK 1/2 (p-ERKl/2) was examined by western blot. Cell viability was detected using cell proliferation and cytotoxicity kit-8 (CCK8), and cell cycle distribution and proliferating cells were evaluated by the flow cytometry. Cell migration was examined by Transwell assay. Results showed that, compared with the control group, Purmorphamine increased the levels of p-ERK1/2 in concentration-and time-dependent manners (P < 0.01). Co-treated with Purmorphamine and U0126-EtOH or Cyclopamine both decreased the levels of p-ERK1/2 (P < 0.05). RA-FLSs treated with Purmorphamine resulted in alteration of cell cycle distribution, increasing of proliferating cells, cell viability, and migration cells compared to controls (P < 0.01). However, the above phenomenon can be abolished by U0126-EtOH (P < 0.05). The findings suggest that SHH signaling pathway mediates proliferation and migration of RA-FLSs via MAPK/ERK pathway and may contribute to progression of RA. Targeting SHH signaling may have a therapeutic potential in patients with RA.

Predictive utilities of neutrophil gelatinase-associated lipocalin (NGAL) in severe sepsis.

BACKGROUND: We aim to investigate the predictive value of plasma neutrophil gelatinase-associated lipocalin (pNGAL) in patients with severe sepsis. METHODS: A total of 124 patients were enrolled in this observational study. Blood samples were obtained at admission, on day 2 and day 7. Receiver operating characteristic (ROC) curves were generated to assess the utility of pNGAL in prediction of 28-day mortality and need for CRRT. Cox regression curves were built with and without pNGAL for 28-day mortality prediction to determine NGAL's contributive predictive value. RESULTS: Plasma NGAL was significantly increased in non-survivors group on day 2 and 7 and predicted 28-day mortality with AuROC values of 0.675 (95% CI 0.570-0.780) and 0.752 (95% CI 0.619-0.885). Addition of day 2 NGAL to the clinical model resulted in a net reclassification index (NRI) increment of 0.40 (95% CI 0.06-0.75, P = 0.028) for prediction of 28-day mortality. The AuROC of NGAL at admission and day 2 was greater than creatinine in prediction of the need for CRRT. CONCLUSION: Plasma NGAL discriminated 28-day survivors from non-survivors on day 2 and 7 and was a relatively robust predictor of 28-day mortality prediction. Plasma NGAL possibly outperformed creatinine in the prediction of need for CRRT.

Smoothened Regulates Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Activation of Rho GTPase Signaling.

Fibroblast-like synoviocytes (FLSs) acquire aggressive phenotypes characterized with enhanced migration abilities and inherent invasive qualities in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell invasion and metastasis. The objective of this study is to investigate the role of Smo in the modulation of cell migration and explore the underlying molecular mechanism(s). FLSs were isolated from RA synovium. Shh levels were regulated by a Smo agonist (purmorphamine), Smo antagonist (KAAD-cyclopamine), or small interfering RNA targeting the Smo gene (Smo-siRNA) in RA-FLSs. Expression of Smo was detected by real-time PCR and western blot analysis. Cell migration was examined by Transwell assay and activation of Rho GTPases was measured by pull-down assays. Incubation with purmorphamine resulted in a significant increase of cell migration and activation of Rho GTPase signaling compared to controls (P < 0.05). However, treatment with KAAD-cyclopamine or transfection with Smo-siRNA suppressed migration of RA-FLSs and showed an inhibitory effect of Rho GTPase signaling. Together, these results suggest that Smo plays an important role in RA-FLSs migration through activation of Rho GTPase signaling and may contribute to progression of RA, thus, targeting Shh signal may have a therapeutic potential in patients with RA.

Inhibition of smoothened decreases proliferation of synoviocytes in rheumatoid arthritis.

Fibroblast-like synoviocytes (FLSs) contribute to synovial hyperplasia in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell proliferation. The objective of this study was to investigate the role of Smo in RA synoviocyte proliferation. FLSs were isolated from RA synovium. Shh signaling was studied using a Smo antagonist (GDC-0449) and small interfering RNA (siRNA) targeting the Smo gene in FLSs. Cell proliferation was quantified by using kit-8 assay and cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell cycle-related genes and proteins were detected by real-time PCR and western blot. FLSs treated with GDC-0449 or Smo-siRNA showed significantly decreased proliferation compared to controls (P < 0.05). Incubation with GDC-0449 or transfection with Smo-siRNA resulted in a significant increase of G1 phase cells compared to controls (P < 0.05). Cell cycle arrest was validated by the significant increase in cyclin D1 and E1 mRNA expression, decrease in cyclin-dependent kinase p21 mRNA expression in Smo-siRNA transfected cells (P < 0.05). Protein expression of cyclin D1 was also downregulated after Smo gene knockdown (P < 0.05). The results suggest that Shh signaling plays an important role in RA-FLSs proliferation in a Smo-dependent manner and may contribute to synovial hyperplasia. Targeting Shh signaling may help control joint damage in patients with RA.

Investigation of the Upper Airway Anatomy With Ultrasound.

OBJECTIVE: The aims of this study were to describe the relationship between the scanning planes and appearance of the upper airway on sonography and to demonstrate the reliability and reproducibility of sonographic measurements of the upper airway. METHODS: Airway sonoanatomy was recognized by comparing the airway images and the corresponding cadaver's anatomical specimens. Systemic sonographic examination of 267 healthy volunteers was conducted to obtain the sonographic measurement of airway lumen. The reliability and reproducibility studies were conducted in 40 healthy volunteers. RESULT: The air-filled upper airway appeared as a bright heterogeneous hyperechoic line. During deep inspiration, the upper airway lumen expanded to the highest anterior-posterior dimension, whereas during deep expiration, the lateral dimension tended to increase. The sonographic measurements had good reproducibility, with intraclass correlation coefficient ranging from 0.722 to 0.887 and 0.727 to 0.882 for interobserver and intraobserver reliability, respectively. CONCLUSIONS: Ultrasonography can determine the anatomy of the upper airway and perform the quantitative analysis of the upper airway lumen during respiration. The results were encouraging and support the utility of ultrasonography in future airway disorder studies.