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Chemotherapy can improve the prognosis and overall survival of breast cancer patients, but chemoresistance continues a major problem in clinical. Most breast cancer is estrogen receptor (ER) positive but responds less to neoadjuvant or adjuvant chemotherapy than ER-negative breast cancer. The Nogo-B receptor (NgBR) increases the chemoresistance of ER-positive breast cancer by facilitating oncogene signaling pathways. Here, we further investigated the potential role of NgBR as a novel target to overcome glycolysis-dependent paclitaxel resistance in ER-positive breast cancer. NgBR knockdown inhibited glycolysis and promoted paclitaxel-induced apoptosis by attenuating HIF-1α expression in ER-positive breast cancer cells via NgBR-mediated estrogen receptor alpha (ERα)/hypoxia-inducible factor-1 alpha (HIF-1α) and nuclear factor-kappa B subunit (NF-κB)/HIF-1α signaling pathways. A ChIP assay further confirmed that NgBR overexpression not only facilitates ERα binding to HIF-1α and GLUT1 genes but also promotes HIF-1α binding to GLUT1, HK2, and LDHA genes, which further promotes glycolysis and induces paclitaxel resistance. In conclusion, our study suggests that NgBR expression is essential for maintaining the metabolism and paclitaxel resistance of ER-positive breast cancer, and the NgBR can be a new therapeutic target for improving chemoresistance in ER-positive breast cancer.

Background Neratinib plus capecitabine(N + C)has a good effect for HER2-positive metastatic breast cancer (MBC), but considering these tradeoffs in quality of life and cost, the optimal choice of treatment sequencing is unclear. Cost-effectiveness analysis can clearly quantify such tradeoffs to make more informed decisions. Our objective was to evaluate the social cost-effectiveness of the N + C regimen for HER2 positive MBC. METHODS Clinical data were extracted from a randomized controlled trial, NALA (NCT01808573). Patients were randomized into the N + C group or the lapatinib plus capecitabine (L + C) group. A Markov model was established with a 21-day cycle length. Costs were acquired from local hospitals, effect parameters included quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER). RESULTS In the main analysis, the QALY in N + C is 0.04492 higher than that in L + C (N + C, 0.62954 QALY; L + C, 0.58462 QALY). The ICER between N + C and L + C was − 1,796,801.93 CNY/QALY. In the subanalysis, the QALY in N + C is 0.05643 higher than that in L + C (N + C, 0.65047 QALY; L + C, 0.59404 QALY) in the Asian group. The ICER between N + C and L + C was − 1,584,528.96 CNY/QALY. Sensitivity analyses indicated the stability of the model and the impact of utility. CONCLUSION N + C was cost-effective compared with L + C for HER2 positive MBC.

BACKGROUND The mechanical stretch injury imposed by the intravascular intervention contributes to neointimal hyperplasia. Lessening of this damage without the compromise of luminal dilation could be an alternative way to alleviate restenosis. OBJECTIVE We aimed to assess the relationship of lumen diameter and neointimal hyperplasia with inflation pressure using color Doppler ultrasound-guided balloon dilation. METHODS The anteroposterior diameter of the given aortic segment in rabbits was measured by ultrasonography to ensure the similar original diameter. Then they were assigned into three groups with the inflation force at 1, 5, 10 atmosphere pressure (atm), respectively. Balloon dilation and injury of the given aortic segment were performed. Two weeks later, all rabbits were euthanized for histologic evaluation. RESULTS After operation, the lumen diameter of each group enlarged significantly (P< 0.05) with a similar rate of change. However, neointimal area, circumference and hepatocyte growth factor (HGF) positive cells in group with 1 atm were significantly less than those of the other two (P< 0.05). Maximal neointima thickness increased significantly with the elevation of the inflation pressure (P< 0.05). CONCLUSIONS Based on sufficient dilation of the balloon, the balloon inflated with the less pressure caused the similar increase in lumen diameter as the higher pressure but the less neointimal hyperplasia and HGF positive cells.

Background: According to different patients’ subgroups choose optimal maintenance therapy. Methods: 226 Newly Diagnosed Multiple Myeloma (NDMM) patients in our center were included, the patients’ characteristics, survival, response, subgroup analysis, adverse reactions were compared between the patients with or without maintenance, proteasome inhibitor (PI) or immunomodulators (IMiDs) maintenance. And the survival of different maintenance duration of bortezomib-based regimens was also analyzed.Results: The maintenance therapy not only upgraded more patients’ response (34.3 vs. 13.3%, p= 0.006), but also significantly prolonged the patients’ PFS (median PFS: 41.1 vs. 10.5 months, p < 0.001) and OS (median OS: not reached vs. 38.6 months, p < 0.001). Compared with IMiDs, the PFS (median PFS: 43.7 vs. 38.5 months, p = 0.034) and OS (median OS: not reached vs. 78.5 months, p = 0.041) can both benefit from bortezomib-based maintenance. The patients younger than 65 years old with bortezomib-based maintenance significantly prolonged the OS (p= 0.032). Patients achieving the only partial response (PR) after induction and consolidation therapy experienced a significantly longer PFS and OS with bortezomib-based maintenance compared to IMiDs (p= 0.007, 0.002). Besides, the high-risk patients (ISS 2-3, DS 2-3 and RISS 2-3) with bortezomib-based maintenance can benefit PFS (p= 0.002, 0.02, 0.06, respectively) and OS (p=0.059, 0.047, 0.044, respectively) compared with IMiDs. The OS was significantly prolonged in the patients who received ≥12 months of bortezomib-based maintenance than those with maintenance < 12 months (p< 0.001), but no difference was observed in OS between the patients who received the 12-24 or ≥ 24months of bortezomib-based maintenance (p= 0.292).Conclusion: Maintenance therapy can significantly improve the survival of NDMM patients. Bortezomib-based regimens maintenance was more superior to IMiDs in overall PFS and OS. The beneficial effect is most evident in patients achieving the only PR after induction and consolidation therapy, and the high-risk patients. Moreover, younger patients also could benefit from bortezomib-based maintenance in OS. The bortezomib-based maintenance duration lasting 12-24 months after induction and consolidation therapy can reach a satisfactory OS.

Supplemental material, sj-pdf-1-tah-10.1177_2040620720976984 for Acute myeloid leukemia with CPSF6–RARG fusion resembling acute promyelocytic leukemia with extramedullary infiltration by Xiaoyan Han, Chunxiang Jin, Gaofeng Zheng, Yi Li, Yungui Wang, Enfan Zhang, Honghu Zhu and Zhen Cai in Therapeutic Advances in Hematology

Background: In diabetic patients with gastroparesis, the gastric blood supply is often decreased and delayed gastric emptying associating MMCIII absence is the main symptom. Under physiological conditions, motilin has been shown to induce a sustained increase in left gastric artery (LGA) blood flow and initiate MMC phase III simultaneously. The study aimed to elucidating the signal transduction pathways of motilin receptors (MLNRs) in the relaxation of LGA.Methods: MLNR expression in the LGA was analysed by immunohistochemistry. Motilin-induced relaxation of the LGA was tested in a multi-wire myograph system. Effects of inhibitors or blockers in the signal transduction pathway were observed.Results: Immunohistochemical and immunofluorescence staining showed that the MLNRs were on the membranes of endothelial cells. Motilin relaxed U46619 pre-contracted canine LGA rings in a concentration-dependent manner, with an EC50 value of 9.010 ± 0.789 × 10−8 M. Motilin’s effect was inhibited by denuded endothelium but not by muscarinic receptor inhibitors. The effect was selectively and competitively inhibited by Phe-cyclo[Lys-Tyr(3-tBu)-Ala-]•trifluoroacetate (GM-109; MLNR antagonist) and completely or partially inhibited by inhibitors of the G protein–phospholipase C–inositol trisphosphate (G pr–PLC–IP3) and nitric oxide synthase–nitric oxide–soluble guanylyl cyclase (NOS–NO–sGC) signal transduction pathway, inhibitors of cyclooxygenase and myoendothelial gap junction, blockers of the potassium channel and low/free Ca2+ Krebs solutions, but not by inhibitors of protein kinase C, protein kinase A or L-type voltage-operated Ca2+ channel.Conclusions: MLNRs were on the membranes of endothelial cells of canine LGA. The main intracellular signal transduction pathway was motilin–MLNR–G pr–PLC–IP3–NOS–NO–sGC–cGMP. These results may provide a new theoretical basis for research on diabetic gastroparesis.

(1) To compare the American College of Radiology (ACR) thyroid imaging reporting and data system (TIRADS) and American Thyroid Association (ATA) guidelines for thyroid nodules with regard to diagnostic performance and effectiveness at reducing the number of fine-needle aspiration (FNA) biopsies and to preliminarily discuss the reasons for the differences and (2) to compare the diagnostic performance of the two guidelines in the subgroup of nodules

Background The aim of the present study was to establish a prognostic model for the survival of children with osteosarcoma (OS). Methods The mRNA expression and clinical characteristics of pediatric patients with OS were extracted from the Therapeutically Available Research to Generate Effective Treatments (TARGET) database. After genes with differential mRNA expression were identified, univariate and multivariate Cox analyses were performed, and a prognostic model of pediatric OS was established. The prognostic values of a 7-mRNA signature were evaluated using the receiver-operating characteristic (ROC) curve in pediatric patients with OS. Results A total of 19,496 differentially expressed mRNAs were identified, including 267 upregulated mRNAs and 104 downregulated mRNAs. After univariate and multivariate Cox analyses, seven mRNA species (SCGB3A1, MUC17, ADH1B, KRT83, RP1-37E16.12, FIGF, and SFTPD) were found to be closely associated with survival. These mRNA species were mainly enriched in glycolysis/gluconeogenesis, arachidonic acid metabolism, cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, tight junction, and complement and coagulation cascade pathways. A predictive model using the sum of independent prognostic values of the seven mRNA species as the risk score was proposed. The risk score was calculated as follows: risk score = 0.242257 × SCGB3A1 + 0.168999 × MUC17 + 0.415514 × ADH1B + 0.488864 × KRT83 + 0.360864 × RP1-37E16.12 – 0.2991 × FIGF – 0.39576 × SFTPD. Pediatric patients with OS were assigned to low- and high-risk groups based on the risk score. The ROC curve analysis showed that the 7-mRNA prediction model performed well [area under the curve (AUC): 0.858]. Conclusions A 7-mRNA signature has the potential to predict the prognosis of pediatric patients with OS, and therefore warrants further validation.

OBJECTIVES To analyze the clinical significance of using hepatic transit time (HTT) to evaluate portal vein pressure in gastroesophageal varices patients. METHODS For the observation group, we enrolled 50 gastroesophageal varices patients who had received esophagogastric variceal embolization in our hospital between January 2015 and February 2018. Patients without liver disease populated the control group and were recruited during the same time period. All patients underwent contrast-enhanced sonography. In the observation group, free portal pressure (FPP) was detected during esophagogastric variceal embolization with ultrasound guidance. Differences in hepatic artery-hepatic vein transit time (HA-HVTT), portal vein-hepatic vein transit time (PV-HVTT), and parenchyma-hepatic vein transit time (PA-HVTT) were compared between groups. Correlations between HA-HVTT, PV-HVTT, PA-HVTT, and FPP in the observation group were analyzed using the Pearson coefficient and linear regression analysis. RESULTS HA-HVTT (t = 5.078; P

Currently, multifunctional nanotechnology is strongly expected to improve the prospect of treatment and diagnosis. In this study, we synthesized epidermal growth factor (EGFR)-targeted phase-changeable polymer nanoparticles (C-HPNs) loaded with two drugs (C225 and 10-HCPT) for specific tumor targeting, synergistic chemotherapy, and ultrasound imaging under low-intensity focused ultrasound (LIFU). Cetuximab (C225), an EGFR-targeted monoclonal antibody, was conjugated on the surface of the nanoparticles, leading to a significantly high binding affinity to EGFR-overexpressing anaplastic thyroid C643 cells both in vitro and in vivo. As expected, an increase of more than 3- to 4-fold in the release rates of 10-HCPT was observed after LIFU irradiation in vitro, demonstrating that LIFU could enhance the release of drugs from the nanoparticles. Combined treatment with C-HPNs and LIFU showed excellent inhibition of cell proliferation in vitro, as well as a remarkable therapeutic effect in vivo. Moreover, the combined treatment simultaneously enhanced ultrasound imaging by LIFU-induced acoustic droplet vaporization (ADV). In conclusion, C225-modified and phase-changeable nanoparticles combined with LIFU exhibited great promise for concurrent targeted ultrasound molecular imaging and effective synergistic antitumor therapy.

Metformin, a common therapeutics for type 2 diabetics, was recently demonstrated to possess antitumor activity in various cancer types. However, its therapy effect in renal cell carcinoma (RCC) still remains controversial. In this study, we found that metformin treatment in RCC cells lead to activation of AMPK, which suppressed the cell proliferation under normal condition, but enhanced cell proliferation under glucose deprivation (GD) condition. Depletion of AMPK by siRNA abolished the proliferation effect of MF under GD condition. Mechanistic investigations revealed that the effect of AMPK on cell proliferation under GD condition is dependent on its nuclear translocation. Moreover, the nuclear AMPK recruits PKM2 and β-Catenin to form a complex, which promotes the transcription of cell proliferation related genes, including CCND1 and c-Myc. Furthermore, depletion of PKM2 or β-Catenin abrogated the proliferative effects of metformin under GD condition. And inhibition of PKM2 also re-sensitized the A498 xenograft in response to metformin treatment. Together, our results suggested that combined of AMPK activation and PKM2 depletion or inhibition can achieve better therapeutic effect for RCC patients.

YWHAZ (14-3-3ζ) plays crucial roles in regulating proliferation, apoptosis, migration, and invasion of gastric cancer (GC) cells. However, its extensive roles and potential mechanisms in GC cells remain unknown, and need to be researched deeply. In this study, we focus on the role of miR-375/YWHAZ axis in migration, invasion and epithelial-to-mesenchymal transition (EMT) of GC cells. YWHAZ level was assessed by western blot and qPCR assays in GC cells. Scratch and transwell assays were used to determine the migration and invasion of GC cells. The protein levels of correlative molecules were detected by western blot. The regulation of miR-375 on the expression of its target gene YWHAZ was verified by dual-luciferase report system. According to the results, knockdown of YWHAZ inhibited the migration, invasion and EMT of GC cells. Moreover, silencing of YWHAZ restrained the activation of wnt/β-catenin signalling pathway. YWHAZ was confirmed to be a target gene of miR-375, and its expression was regulated by miR-375 in GC cells. Transfection of miR-375 inhibitor promoted the migration, invasion, EMT and activation of wnt/β-catenin pathway in GC cells, which was suppressed by inhibition of YWHAZ. Taken together, this study suggests that miR-375/YWHAZ axis may be served as a novel therapeutic target for GC patients.

The purposes of this study were to compare pancreatic shear-wave velocity (SWV) in subjects with and those without diabetic microvascular complications and to investigate the feasibility of pancreatic SWV in evaluating diabetic microangiopathy.SWV measurements were prospectively performed in 115 patients with diabetes mellitus and 115 healthy persons by use of acoustic radiation force impulse imaging. Patients with diabetes were divided into subgroups with and without microangiopathy. Pancreatic SWV was compared in three groups. Factors associated with increased SWV were studied.Pancreatic SWV increased significantly in the subgroups with diabetes mellitus compared with the control group (p0.01). Especially, the SWV in the pancreatic body was significantly higher when microangiopathy was present (p0.01). In patients with diabetes, microangiopathy (standardized β = 0.208, p = 0.022), age (standardized β = 0.265, p = 0.004), and total cholesterol level (standardized β = 0.223, p = 0.011) were positively and markedly correlated with high SWV in the pancreatic body.The increased SWV in the pancreatic body was significantly related to the presence of microangiopathy. It is feasible to use SWV in the pancreatic body to evaluate diabetic microangiopathy.

The present study investigated the effects of in vivo gene transfer of human hepatocyte growth factor (hHGF) on neointima formation in rabbit abdominal aortae following ultrasound‑guided balloon injury. New Zealand white rabbits were randomly divided into four groups: endothelium injury alone (EI), endothelium injury with control vector transfection (EI‑V), endothelium injury with hHGF transfection (EI‑HGF), and hHGF transfection alone without endothelium injury (HGF). Endothelial injury was established by scraping the abdominal aortic wall using a balloon catheter under the guidance of a transabdominal ultrasound. hHGF gene transfer was performed 7 days following injury. hHGF mRNA and protein expression levels were determined at 3, 7, 14 and 21 days following transfection. Neointima formation was assessed by histopathological analysis at 14 and 28 days following injury. hHGF mRNA and protein expression levels were detected in the target abdominal aortae in EI‑HGF and HGF groups with the greatest levels observed 3 days following transfection, and their levels dropped below detection limits at 21 days following transfection. hHGF was not detectable in the EI and EI‑V groups throughout the experiment. The neointimal area and the neointima to media ratio in the EI‑HGF group were significantly decreased compared with those in the EI or EI‑V group at 14 days following injury. However, no differences were observed at 28 days following injury. The present study demonstrated that in vivo hHGF gene transfer inhibits the early formation of neointima in balloon‑injured rabbit abdominal aortae.

The aim of this study was to noninvasively explore pancreatic morphological and mechanical changes in diabetic patients with or without microangiopathy and to investigate the clinical correlations of pancreatic stiffness or size with diabetic microangiopathy.A total of 213 type 2 diabetic patients with / without microangiopathy (91/122) were prospectively enrolled. Microangiopathy included diabetic retinopathy, diabetic nephropathy and diabetic peripheral neuropathy. Each subject underwent pancreatic ultrasonography and elastography. The shear wave velocity (SWV) and thickness of the head, body and tail were measured and compared. Receiver operating characteristic (ROC) curves was performed in the diagnosis of microangiopathy. Risk factors of the occurrence of more microvascular complications were explored.The SWV in pancreas increased significantly in patients with microangiopathy (P0.01) while the thickness was similar in all patients. The area under ROC curve for the SWV in pancreatic body was greatest (0.747) and the sensitivity, specificity were 73.0, 70.9 %. There was a significant shift towards the occurrence of more microvascular complications for patients with increasing of the SWV in pancreatic body (OR 39.25), long duration of diabetes (OR 1.077), aging (OR 1.039) and elevation of microalbuminuria (OR 1.004).The SWV in pancreatic body was significantly high in diabetic patients with microangiopathy and was prominently correlated with the number of microvascular complications. The SWV in pancreatic body may be considered as a potential marker for diabetic microangiopathy and its occurrence.

Circular RNAs (circRNAs), a novel subgroup of non-coding RNAs (ncRNAs), have been reported in human cancers due to their significant regulatory roles. CircRNA Hippocampus Abundant Transcript 1 (circHIAT1) has been studied in clear cell renal cell carcinoma. However, whether it can regulate the tumorigenesis of hepatocellular carcinoma (HCC) remains unclear. The expression level of circHIAT1 in HCC samples and cell lines was measured by qRT-PCR analysis. CircHIAT1 was expressed at a significantly low level in cancerous samples. Based on Kaplan-Meier survival analysis, we determined a positive correlation between the downregulation of circHIAT1 and the poor overall survival of HCC patients. Using subcellular fractionation and RNA FISH assay, we identified the predominant cytoplasmic localization of circHIAT1. Both in vitro and in vivo experiments demonstrated the suppressive effect of circHIAT1 on the HCC cell growth. Mechanistically, circHIAT1 acted as the miR-3171 sponge to upregulate PTEN in HCC. Finally, rescue assays demonstrated the role of circHIAT1/miR-3171/PTEN pathway in regulating HCC cell growth. Taken together, this study revealed the novel mechanism of circHIAT1 in HCC.

Background Motilin’s role in the regulation of vascular tone and hemodynamic besides gastrointestinal motility is concerned. This study aimed to investigate the expression of motilin receptors in gastrointestinal arteries and motilin-induced relaxation. Material and Methods The expression of motilin receptors in the left gastric artery (LGA), superior mesenteric artery (SMA), and inferior mesenteric artery (IMA) of adult dogs (1.5–5 years old) were analyzed by immunochemistry, RT-PCR, and western blotting. Motilin’s effects on the gastrointestinal arteries were evaluated in a multi-wire myograph system. Results Immunohistochemical staining showed that motilin receptor was expressed on the membranes of endothelial cells with the fluorescence intensity LGA > SMA > IMA (P The motilin receptor's mRNA and protein expression levels shared the same distribution patterns as it in fluorescence intensity (P In isolated LGA preparations precontracted with U46619 (a thromboxaneA2 analog), motilin induced a concentration-dependent relaxation, and the EC50 was 8.8 × 10−8 ± 0.9 × 10−8 M. Motilin-induced relaxation on the three arteries also shared the same pattern as it in fluorescence intensity (P Conclusions Motilin receptors are expressed differentially on the membranes of endothelial cells in dog gastrointestinal arteries with a significantly high expression in the LGA. Motilin-induced relaxation is endothelium- and motilin receptor-dependent. The motilin receptor expressed on the endothelial cell membrane of the LGA is the molecular basis for motilin regulating gastric blood flow under physiological conditions in dogs.

Extracranial internal carotid artery aneurysms (EICAA) are rare and can elicit various neurologic symptoms. Here, we present a case of a saccular EICAA compressing its proximal parent internal carotid artery (ICA). Ultrasonography demonstrated the proximal ICA stenosis and the "tardus-parvus" Doppler waveform downstream. The patient underwent aneurysmectomy and graft interposition. The histologic analysis highly supported an atypical fibromuscular dysplasia. Although this patient only showed a neck mass, the reduced ipsilateral cerebral blood supply was a potential cause for neurologic symptoms. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:116-120, 2017.

OBJECTIVES: To establish and verify a simple noninvasive model based on the left gastric vein (LGV) to predict the grade of esophageal varices (EV) and high-risk EV (HEV), to facilitate clinical follow-up and timely treatment. METHODS: We enrolled 320 patients with B-viral cirrhosis. All patients underwent endoscopy, laboratory tests, liver and spleen stiffness (SS), and ultrasonography. HEV were analyzed using the χ2 test/t test and logistic regression in the univariate and multivariate analyses, respectively. EV grades were analyzed using the variance/rank-sum test and logistic regression. A prediction model was derived from the multivariate predictors. RESULTS: In the training set, multivariate analysis showed that the independent factors of different EV grades were SS, LGV diameter, and platelet count (PLT). We developed the LGV diameter-SS to PLT ratio index (LSPI) and LGV diameter/PLT models without SS. The area under the receiver operating characteristic curve of the LSPI for diagnosis of small EV, medium EV, large EV, and HEV was 0.897, 0.899, 0.853, and 0.954, respectively, and that of the LGV/PLT was 0.882, 0.890, 0.837, and 0.942, respectively. For the diagnosis of HEV, the negative predictive value was 94.07% when LSPI < 19.8 and the positive predictive value was 91.49% when LSPI > 23.0. The negative predictive value was 95.92% when LGV/PLT < 5.15, and the positive predictive value was 86.27% when LGV/PLT > 7.40. The predicted values showed similar accuracy in the validation set. DISCUSSION: Under appropriate conditions, the LSPI was an accurate method to detect the grade of EV and HEV. Alternatively, the LGV/PLT may also be useful in diagnosing the varices when condition limited.

Purpose To summarize the published literature on microwave ablation (MWA) for the treatment of benign thyroid nodules and papillary thyroid microcarcinomas, and to evaluate the effectiveness and safety of MWA as a novel treatment strategy. Methods Two independent authors carried out the literature search using four databases, including PubMed, Embase, Cochrane, and Web of Science. The meta-analysis included prospective and retrospective data that compared pre-treatment values to post-treatment outcomes. Results From the 33 original articles, seven studies met the inclusion criteria for this meta-analysis. Of these, five were retrospective studies, two were prospective trials, one was controlled study, and one was a multi-center study. The results showed significant improvements in nodule volume, clinical symptom scores, and beauty scores between the baseline and final follow-up visits. In all of the studies, the most common adverse effects were hematomas, unbearable pain, and transient or permanent voice change in 3.8%, 2.2%, and 4.6% of patients, respectively. None of these incidents resulted in hospitalization or death. Conclusions MWA is effective and safe for the treatment of benign thyroid nodules and papillary thyroid microcarcinomas. However, future studies should compare the efficacy of MWA, RFA, and surgical intervention.

To assess the safety and efficacy of microwave ablation (MWA) for primary papillary thyroid microcarcinoma (PTMC) with a large sample of 185 patients. A total of 185 patients underwent MWA for 206 primary PTMC nodules. They received ultrasound follow-up at 1, 3, 6, and 12 months after MWA and every 6 months thereafter. Nodule volumes were calculated at each follow-up and compared with those before MWA. Additionally, the volume reduction rate (VRR) of the nodules was calculated. Patients’ thyroid functions were tested before and 1 month after MWA. The mean follow-up time of the 185 patients was 20.7 ± 8.8 months (range 12–36 months). During the follow-up period, the mean volume of the 206 nodules was 100.1 ± 92.9 mm3 (range 3.6–423.9) before MWA, which decreased to 2.2 ± 5.6 mm3 (range 0–20.3 mm3) after MWA (P = 0.000). The mean VRR of the nodules was 98.65 ± 3.60% after MWA (range 83.85–100%). One hundred and seventy four of 206 nodules (84.5%) were fully absorbed. Compared with the preoperative results, no significant variation in thyroid function was observed 1 month after MWA. Thirty-eight patients (20.5%) had different types of complications, ranging from minor to major. Five patients (2.7%) had hoarseness, 11 patients (5.9%) had bleeding, 21 patients (11.4%) had earache or toothache, and one patient had another lesion 1 month after MWA. This preliminary study suggests that MWA is safe and effective in the treatment of primary PTMC and offers a new alternative for clinical treatment.

Hepatic growth factor (HGF) has been widely used in studies on arterial remodeling after injury, and results turn out to be inconsistent. The changes of endogenous HGF expression after injury also remain controversial. This study clarified the role of exogenous human HGF (hHGF) gene transfer in neointimal hyperplasia and investigated the associated alterations of endogenous HGF and c-Met expressions under endothelial denudation with or without hHGF gene transfer using a balloon-injured rabbit aorta model. Sixty-one rabbits were randomly divided into normal controls, endothelial injury, endothelial injury with hHGF, or the control vector gene transfer groups. On weeks 1, 2, 4, and 8 after injury, neointimal hyperplasia and endothelialization were evaluated by the ratio of neointimal area to medial area (N/M ratio), CD31-positive staining, α-smooth muscle actin, and endothelial nitric oxide synthase expressions using histological analysis, immunohistochemistry staining, or real-time quantitative reverse transcriptase polymerase chain reaction. Endogenous rabbit HGF (rHGF) and c-Met expressions were detected with immunohistochemistry staining and quantitative reverse transcriptase polymerase chain reaction. It was found that expressions of endogeneous rHGF and c-Met in endothelial injury upregulated with peak levels on week 2 or week 4 after injury (p 0.01). On week 1 after hHGF transfer, neointimal hyperplasia was significantly inhibited (p 0.001), with decreased α-smooth muscle actin expression (p 0.05) and improved endothelial cells regeneration and function (p 0.01). More remarkable overexpression of endogenous rHGF and c-Met mRNAs were detected, and lowered positive staining of rHGF and c-Met was shown in the neointima (p 0.05). These results demonstrated hHGF gene transfer induced further overexpression of endogenous rHGF and c-Met mRNAs but lowered immunoreactivities of rHGF and c-Met in the neointima, thus leading to significant attenuation of neointimal hyperplasia.

YWHAZ (14-3-3ζ) has been reported to be a prognostic marker for various tumors and play a crucial role in many oncogenic processes, including proliferation, migration and invasion. However, the functional role and mechanism of YWHAZ in gastric cancer (GC) are not in detail and still remain to be studied. In the present study, the endogenous expression of YWHAZ in gastric cancer cell line BGC-823 was silenced by YWHAZ-specific short hairpin RNA (shRNA). Our data showed that YWHAZ silencing resulted in cell cycle arrest in BGC-823 cells. Further, YWHAZ-silenced BGC-823 cells acquired increased apoptosis rate, which was confirmed by increased levels of cleaved caspase-3, cleaved PARP, and Bax, and decreased level of Bcl-2. Suppression of YWHAZ also promoted autophagy, confirming by the upregulation of LC3II /LC3I ratio, and downregulation of p62 level. Moreover, YWHAZ suppression inhibited the activation of PI3K/AKT/mTOR signaling pathway in BGC-823 cells. LY294002 (PI3K/AKT inhibitor, 200 nM) further promoted YWHAZ silencing-induced apoptosis and autophagy in BGC-823 cells, while insulin-like growth factor-1 (IGF-1; PI3K/AKT agonist, 10 ng/ml) had the opposite role. Finally, suppression of YWHAZ inhibited the growth of the xenograft tumor in vivo. This study provides extended evidence that YWHAZ can be a potential therapeutic target for GC.

In this paper, we extended the measurement method of mid-frequency wavefront error to spherical and aspherical components. Some influence factors like the system error of interferometer, environment variation, surface parallelism of optics, polarizations of interferometer illumination, and the wavefront distribution of optics are analyzed in detail. Some optimized measurement strategies for different kinds of optics are suggested. Finally, experimental measurements on flat optics, spherical and aspherical optics are performed to testify the suggested measurement methods, respectively.

Background & Aims: Gastric blood flow exhibits cyclical increases in phase with the interdigestive contractions and secretion of the stomach in dogs. The aim of this study is to clarify the regulatory role of motilin in interdigestive gastric blood flow in dogs. Methods: Blood flow of the left gastric (LGA) and superior mesenteric (SMA) arteries were measured by ultrasound transit-time blood-flow meters in 5 conscious dogs. Motilin was infused intravenously with or without Phe-cyclo[Lys-Tyr(3-tBu)-βAla-] · trifluoroacetate (GM-109; motilin antagonist), granisetron (5-HT 3 antagonist), atropine, hexamethonium (C6), phenoxybenzamine, propranolol, or cimetidine. Results: Motilin (12.5, 25, 50, and 100 pmol · kg −1 · h −1 ) induced LGA blood-flow responses, consisting of a sustained increase and a rapid phasic change coupled with a contraction, without affecting the blood pressure, heart rate, and SMA blood flow. GM-109 completely abolished the LGA, motility, and secretory responses to motilin (100 pmol · kg −1 · h −1 ). Atropine abolished motilin-induced gastric contractions, secretion, and phasic changes of LGA blood flow but failed to affect the sustained flow increase. However, atropine partially inhibited the LGA responses to lower doses of motilin. The LGA flow responses to motilin were not inhibited by granisetron, C6, α-adrenergic, β-adrenergic, or H 2 blockers. Motilin induced significantly larger gastric vasodilatation than the equivalent doses of VIP. Conclusions: Motilin has a potent and selective gastric vasodilator effect, which appears to be mediated by both cholinergic and noncholinergic mechanisms. Motilin plays an important role in the regulation of interdigestive gastric blood flow in dogs. GASTROENTEROLOGY 2002;123:1578-1581

The effects of human alpha-calcitonin gene-related peptide (alpha-CGRP) and beta-CGRP on pancreatic arterial (PA), superior mesenteric (SMA) and left gastric arterial (LGA) blood flows were studied by ultrasound transit-time blood flow meters in five conscious dogs. Intravenous injections of alpha-CGRP and beta-CGRP (5-200 pmol/kg) induced a dose-related increase in PA flow and a dose-related decrease in its resistance. At lower doses, alpha-CGRP was more potent than beta-CGRP, but their maximal responses were similar. The blood flow responses to alpha-CGRP (200 pmol/kg) were 153% of the basal flow in LGA, 313% in PA, and 534% in SMA, while those to VIP (100 pmol/kg) were 467% in LGA, 953% in PA and 163% in SMA. Somatostatin reduced blood flow in all arteries. alpha-CGRP, but not beta-CGRP, at higher doses induced gastric contractions and pancreatic protein-rich secretion, which were blocked by atropine. These results suggest that CGRP in perivascular nerves in the pancreas may regulate pancreatic blood flow in dogs but its physiological function remains to be studied.

To define the stoichiometry and molecular identity of the Cl−/HCO3− exchanger in the apical membrane of pancreatic duct cells, changes in luminal pH and volume were measured simultaneously in interlobular pancreatic ducts isolated from wild-type and Slc26a6-null mice. Transepithelial fluxes of HCO3− and Cl− were measured in the presence of anion gradients favoring rapid exchange of intracellular HCO3− with luminal Cl− in cAMP-stimulated ducts. The flux ratio of Cl− absorption/HCO3− secretion was ∼0.7 in wild-type ducts and ∼1.4 in Slc26a6−/− ducts where a different Cl−/HCO3− exchanger, most likely SLC26A3, was found to be active. Interactions between Cl−/HCO3− exchange and cystic fibrosis transmembrane conductance regulator (CFTR) in cAMP-stimulated ducts were examined by measuring the recovery of intracellular pH after alkali-loading by acetate prepulse. Hyperpolarization induced by luminal application of CFTRinh-172 enhanced HCO3− efflux across the apical membrane via SLC26A6 in wild-type ducts but significantly reduced HCO3− efflux in Slc26a6−/− ducts. In microperfused wild-type ducts, removal of luminal Cl−, or luminal application of dihydro-4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid to inhibit SLC26A6, caused membrane hyperpolarization, which was abolished in Slc26a6−/− ducts. In conclusion, we have demonstrated that deletion of Slc26a6 alters the apparent stoichiometry of apical Cl−/HCO3− exchange in native pancreatic duct. Our results are consistent with SLC26A6 mediating 1:2 Cl−/HCO3− exchange, and the exchanger upregulated in its absence, most probably SLC26A3, mediating 2:1 exchange.

Objectives: Mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with chronic pancreatitis in Caucasians. We developed a simple method for measuring finger sweat chloride concentration to test whether CFTR dysfunction underlies chronic pancreatitis in Japan where cystic fibrosis (CF) is rare. Methods: We studied 25 patients with chronic (21 alcoholic and 4 idiopathic) pancreatitis and 25 healthy volunteers. Sweat chloride concentrations were measured by a finger sweat chloride test. We analyzed DNA for 20 common CFTR mutations in Europeans, 9 CF-causing mutations in Japanese, and 2 polymorphic loci, a poly-T tract and (TG) repeats, at intron 8. Results: Thirteen patients (52%) had sweat chloride levels >60 mmol/L, a level consistent with CF, while only 4 (16%) healthy subjects exceeded this level. The 29 CF mutations and the 5T allele were detected in neither the patients nor controls. The (TG) 12 allele was common in both the patients (58%) and controls (48%). The (TG) 12/12 genotype was common in alcoholic pancreatitis (29%) compared with the (TG) 11/11 (10%). Patients with the (TG) 12/12 genotype had significantly higher sweat chloride concentrations than the controls. Conclusion: CFTR dysfunction as evidenced by a finger sweat chloride test is present in about half of Japanese patients with chronic pancreatitis, suggesting that this test may be useful for detecting the high-risk group. A higher proportion of the (TG) 12 allele may be a genetic background for elevated sweat chloride concentrations in Japanese patients.

The regulatory mechanisms of postprandial pancreatic hyperemia are not well characterized. The aim of this study is to clarify the role of cholecystokinin (CCK) in the intestinal phase of pancreatic circulation. Pancreatic, gastric, and intestinal blood flows were measured by ultrasound transit-time blood flowmeters in five conscious dogs. Pancreatic and gastric secretion and blood pressure were also monitored. Synthetic CCK octapeptide (CCK-8) or gastrin heptadecapeptide (gastrin-17) was infused intravenously, and milk was infused into the duodenum with or without loxiglumide, a specific CCK-A receptor antagonist. CCK-8 induced dose-related increases of pancreatic, but not gastric or intestinal, blood flow and protein secretion without affecting systemic blood pressure. Gastrin-17 did not affect pancreatic blood flow. An intraduodenal infusion of milk increased pancreatic and intestinal blood flows and pancreatic protein secretion. Loxiglumide completely inhibited pancreatic blood flow and protein responses to CCK-8 and milk but not the intestinal blood flow response. CCK is a potent and specific pancreatic vasodilator, with its effect mediated by CCK-A receptors. CCK plays an important role in the regulation of the intestinal phase of the pancreatic circulation in dogs.

High-power laser system has a requirement for the medium and low spatial wavefront errors of the transmitted wavefront of the spatial filter, which is a spherical lens with long focal length (> 10 m) and large aperture (> 400×400 (mm)). Two interferometric methods are analyzed and compared for testing the medium and low spatial wavefront errors of the long focal length lens with an instantaneous interferometer, using large -aperture plane mirror and concave mirror as retroflectors, respectively. The two kinds of beam path -arrangements are designed using ray tracing method. Wavefront aberration and modulation transfer function are used as merit functions. The reason for their different ability to test the wavefront is also analyzed. To evaluate the -feasibility of test methods, tolerances analyses are performed to determine the tolerances demanding the fabrication and assembly of each optical element. It is proved that a relatively short optical path with a large aperture concave mirror is satisfied for testing the medium and low spatial wavefront errors of the transmitted wavefront of the spatial filter.