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The cap geometry and formation mechanism play a key role in influencing the hole-making quality on the bore exit side and must be the focus of research in orbital drilling of aeronautical metal materials. For a "bowl shape" cap geometry formed in orbital drilling process, the corresponding undeformed cap periphery geometry, generated by the cap periphery cutting edges, is simulated and given the parametric description. Especially, the cap periphery is simplified as a simply supported annular plate under uniform load with arbitrary loading radius based on the characteristics of the cap periphery shape and mechanical analysis of processing. Then its unified plastic limit analysis is developed. The ultimate load, stress field, and plastic deformation at the periphery of the cap are derived from the unified strength theory. Furthermore, the numerical solutions are obtained in terms of the Tresca yield, Huber–von Mises, and twin-shear yield criteria. The conclusions enabled an in-depth understanding of the cap periphery formation mechanism in the orbital drilling of holes from the unified plastic limit analysis perspective. [ABSTRACT FROM AUTHOR]

Purpose: Inflammation associated endothelial cell (EC) dysfunction is key to atherosclerotic disease. Recent studies have demonstrated a protective role of amitriptyline in cardiomyocytes induced by hypoxia/reoxygenation. However, the mechanism by which amitriptyline regulates the inflammatory reaction in ECs remains unknown. Thus, the aim of this study was to investigate whether amitriptyline protects against inflammation in TNF-α-treated ECs. Methods: HUVECs were incubated with amitriptyline (2.5 μM) or TNF-α (20 ng/ml) for 24 h. EdU, tube formation, transwell, DHE fluorescence staining, and monocyte adhesion assays were performed to investigate endothelial function. Thoracic aortas were isolated from mice, and vascular tone was measured with a wire myograph system. The levels of ICAM-1, VCAM-1, MCP-1, phosphorylated MAPK and NF-κB were detected using western blotting. Results: Amitriptyline increased the phosphorylation of nitric oxide synthase (eNOS) and the release of NO. Amitriptyline significantly inhibited TNF-α-induced increases in ASMase activity and the release of ceramide and downregulated TNF-α-induced expression of proinflammatory proteins, including ICAM-1, VCAM-1, and MCP-1 in ECs, as well as the secretion of sICAM-1 and sVCAM-1. TNF-α treatment obviously increased monocyte adhesion and ROS production and impaired HUVEC proliferation, migration and tube formation, while amitriptyline rescued proliferation, migration, and tube formation and decreased monocyte adhesion and ROS production. Additionally, we demonstrated that amitriptyline suppressed TNF-α-induced MAPK phosphorylation as well as the activity of NF-κB in HUVECs. The results showed that the relaxation response of aortic rings to acetylcholine in the WT-TNF-α group was much lower than that in the WT group, and the sensitivity of aortic rings to acetylcholine in the WT-TNF-α group and WT-AMI-TNF-α group was significantly higher than that in the WT-TNF-α group. Conclusion: These results suggest that amitriptyline reduces endothelial inflammation, consequently improving vascular endothelial function. Thus, the identification of amitriptyline as a potential strategy to improve endothelial function is important for preventing vascular diseases. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness and safety of endoscopic resection and various suturing methods to treat non-ampullary duodenal submucosal tumors (NAD-SMTs). Design: We performed a retrospective observational study of patients with NAD-SMTs who underwent endoscopic resection at Zhongshan Hospital, Fudan University, China, between June 2017 and December 2020. Data on patient characteristics, treatments and follow-up results were collected. The association between clinicopathologic characteristics and different suturing methods or adverse events were analyzed. Results: Of 128 patients analyzed, 26 underwent endoscopic mucosal resection (EMR), 64 underwent endoscopic submucosal excavation (ESE), and 38 underwent endoscopic full-thickness resection (EFTR). EMR and ESR are both appropriate for non-full-thickness lesions, whereas ESE is more appropriate for tumors located in the bulb or descending duodenum. Gastric tube drainage is more strongly recommended after ESE. Satisfactory suturing is also vital endoscopic resection of NAD-SMTs. Metallic clips are often used in EMR or ESE of non-full-thickness lesions. The pathological findings revealed that the full-thickness lesions were predominantly gastrointestinal stromal tumors (GIST), Brunner's tumor or lipoma, and the surgeons usually used purse-string sutures to close the wounds. The operation time was longer for purse-string suture closure than metallic clip closure. Eleven patients had complications. Risk factors for adverse events included large-diameter tumor (≥ 2 cm), location in the descending part of the duodenum, involvement of the fourth layer of the duodenal wall, EFTR, and GIST. Conclusions: Endoscopic resection of NAD-SMTs is effective but is associated with a high incidence of complications due to their anatomical peculiarities. Preoperative diagnosis is quite important. Careful selection of treatment and suturing methods are necessary to reduce the risk of adverse effects. Given the increased frequency of severe complications during or following duodenal endoscopic resection, this procedure should be performed by experienced endoscopists. [ABSTRACT FROM AUTHOR]

Background and aims: Peroral endoscopic myotomy (POEM) is a promising endoscopic technique for achalasia. We aimed to establish a regression model and develop a simple nomogram to predict the technical difficulty of POEM in a single center with large volume cases. Methods: 3385 achalasia patients treated with POEM were included, and the technical difficulty was systemically evaluated. All of them were randomized into the training cohort (n = 1693) or internal validation cohort (n = 1692). Then, the prediction model and nomogram were proposed based on multivariate logistic regression analysis in the training cohort and assessed in the validation cohort. Results: Of 3385 patients, technical difficulty happened in 417 (12.32%) cases. In the training stage, six factors were weighted based on the β coefficient from the regression model, including age, disease duration, sigmoid esophagus, mucosal edema, submucosal fibrosis, and tunnel length. The patients were categorized into low-risk (< 0.1), medium-risk (0.1–0.25), and high-risk (> = 0.25) groups. Our score model performed satisfying discrimination with the areas under the receiver-operating characteristic curve (AUC) of 0.743 (95% confidence interval (CI), 0.701–0.785) and calibration with goodness of fit in the Hosmer–Lemeshow test (P = 0.088) in internal validation. Conclusions: The prediction model and nomogram demonstrated good performance in predicting the technical difficulty of POEM. [ABSTRACT FROM AUTHOR]

Cerium oxalate hydrate particles were synthesized by precipitation technique under external magnetic field with respective intensities of 0, 0.1, 0.3, and 0.6 T. The particle morphologies were investigated by scanning electron microscopy (SEM) and transmission electron microscope (TEM). Results show that external magnetic field has a great influence on the growth behavior of cerium oxalate hydrate particles. Rod-like and plate-like cerium oxalate hydrate particles with smaller size are formed without the applying of external magnetic field. However, the extremely big rod-like particles with the average size of 12.47 μm were prepared under external magnetic field of 0.6 T. The increasing magnetic field intensity makes the grain grow quickly. Thermogravimetric analysis supports the presence of 8.5 H2O molecules associated with cerium oxalate. Further, the growth mechanism of cerium oxalate hydrate under external magnetic field was briefly discussed. [ABSTRACT FROM AUTHOR]

As a hot topic today, ferroptosis is closely involved in the progression and treatment of cancer. Accordingly, we built a prognostic model around ferroptosis to predict the overall survival of OSCC patients. We used up to 6 datasets from 3 different databases to ensure the credibility of the model. Then, through differentially expressed, Univariate Cox, and Lasso regression analyses, a model composed of nine prognostic-related differently expressed ferroptosis-related genes (CISD2, DDIT4, CA9, ALOX15, ATG5, BECN1, BNIP3, PRDX5 and MAP1LC3A) were constructed. Moreover, Kaplan–Meier curves, Receiver Operating Characteristic curves and principal component analysis used to verify the model's predictive ability showed the model's superiority. To deeply understand the mechanism of ferroptosis affecting the occurrence, development and prognosis of OSCC, we performed enrichment analysis in different risk groups identified by the model. The results showed that numerous TP53-related, immune-related and ferroptosis-related functions and pathways were enriched. Further immune microenvironment analysis and mutation analysis have once again revealed the correlation between risk score and immunity and TP53 mutation. Finally, the correlation between risk score and OSCC clinical treatment, as well as Nomogram show the brilliant clinical application prospects of the prognostic model. [ABSTRACT FROM AUTHOR]

Background: Submucosal tunneling endoscopic resection (STER) has been widely applied for esophageal submucosal tumors. This large volume study aims to provide a standard landscape of STER-related AEs for reference. Methods: 1701 patients with esophageal SMTs undergoing STER were included at Zhongshan Hospital, Fudan University. Data of clinical characteristics and adverse events were collected and analyzed in depth. Adverse events were recorded by ASGE lexicon and graded by ASGE grading/Clavien–Dindo system. Risk factors for major AEs were analyzed by univariate and multivariate logistic regression. Results: Three hundred and twenty (18.8%) patients with 962 cases of adverse events were observed. Accordingly, 84 (5.0%) were classified as major AEs (moderate and severe) by ASGE grading and 37 (2.2%) were classified as major AEs (grades III–V) by Clavien–Dindo grading. First 1 year operation, distance > 6 cm from incision to tumor, piecemeal resection, partially extraluminal location, mucosal injury, and operation time > 60 min were included in the risk score model for major AEs of STER, with 57.1% sensitivity and 87.5% specificity. Conclusions: STER was a safe procedure for diagnosis and treatment of esophageal SMTs with a total 18.8% incidence of AEs, among which only 5.0% were major AEs requiring therapeutic measurements. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) is a prominent minimally invasive operative technique for treating early gastrointestinal tumors but can result in postoperative bleeding. We conducted a randomized controlled trial to determine whether increasing blood pressure under hemostasis during gastric ESD to identify potential bleeding spots reduces the risk of post-ESD bleeding. Methods: In this randomized, controlled, single-blinded clinical trial, 309 patients with early gastric cancer who were admitted to a hospital to undergo ESD were recruited from March 2017 to February 2018 and were randomized into intervention and control groups. In the control group, patients underwent normal ESD. In the intervention group, we increased patients' blood pressure to 150 mmHg for 5 min using a norepinephrine pump (0.05 μg/kg/min initial dose) after the specimen was extracted during the ESD operation to identify and coagulate potential bleeding spots with hot biopsy forceps. Our primary outcome was the incidence of postoperative bleeding over 60-day follow-up. Results: The incidence of post-ESD bleeding was lower in the intervention group (1.3%, 2/151) than in the control group (10.1%, 16/158, p = 0.01). Deeper tumor invasion was associated with a higher risk of post-ESD bleeding (5.3% in mucosal/submucosal layer 1 group vs. 12.5% in submucosal layer 2/muscularis propria group, p < 0.001). Multi-factor but not univariate analysis showed that proton pump inhibitor administration three times per day may be a better choice than twice per day. Conclusion: Increasing blood pressure under hemostasis during ESD to identify and coagulate potential bleeding spots could reduce the risk of delayed bleeding after gastric ESD. [ABSTRACT FROM AUTHOR]

Background: The surgery for esophageal cancer arising after prior gastrectomy is technically difficult with high morbidity and mortality. Endoscopic submucosal dissection (ESD) is a minimally invasive endoscopic treatment for superficial SCC with high curative resection rate. But few studies are concerned about ESD under these circumstances. The aim of this study was to elucidate the short- and long-term outcomes of ESD for superficial esophageal squamous cell cancer (SCC) in patients with prior gastrectomy.Methods: From January 2009 to January 2019, 37 patients with prior gastrectomy who underwent ESD for superficial esophageal SCC were retrospectively enrolled at the Zhongshan Hospital, Fudan University in Shanghai, China. Rates of en bloc resection, complete resection, curative resection, incidence of postoperative bleeding, perforation and postoperative stricture were evaluated as short-term outcomes. Overall survival, and local recurrence-free survival were evaluated as long-term outcomes.Results: The rate of en bloc resection, complete resection and curative resection were 94.6%, 86.5% and 78.4%, respectively. No perforation was observed. 1 (2.7%) patient experienced postoperative bleeding. During the median observation of 43 months, 3 (8.6%) patients experienced esophageal stricture, successfully managed by balloon dilation. 3(8.6%) patients had local recurrence after ESD with 5-year local recurrence-free survival rate of 91.4%. During the observation period, 4 patients died of other reasons. The 1, 3, 5-year overall survival rates were 97.1%, 97.1% and 91.4%.Conclusions: The short-term outcomes indicate ESD is technically difficult with lower resection completeness in patients after gastrectomy, while the long-term outcomes are rather favorable. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA) profiles were studied in roots of 'Sanhu' tangerine plants with and without Candidatus Liberibacter asiaticus (CLas) infections by using solexa sequencing to investigate the possible involvement of miRNAs in the pathogenesis of Citrus Greening (Huanglongbing) disease. A total of 186 known miRNAs and 71 novel miRNAs were thus identified. Of them, 37 known and 18 novel miRNAs were significantly different in their expression patterns in roots of CLas-free and CLas-infected plants. CLas infection induced de novo expression of 6 known miRNAs and up-regulated the expression of 13 known miRNAs. It also prevented the expression of 11 known miRNAs and down-regulated the expression of 7 others. A total of 316 genes were predicted to be the targets of these differentially expressed miRNAs. Particularly, 34, 28, 21, and 20 genes were predicted to be the respective targets of cre-miR156a, cre-miR396b, cre-miR396g-5p, and cre-miRn70. The predicted putative target genes are known to be involved in stress response, plant growth and development, transcription, and metabolism. Quantitative analyses of the expression of several representative miRNAs and their target genes were generally in agreement with the predicted expression patterns (inverse proportion). Further research to unravel the interactions between these miRNAs and their target genes and determine the associated biological and pathological significance is recommended. [ABSTRACT FROM AUTHOR]

Carbonate reservoirs worldwide are complex in structure, diverse in form, and highly heterogeneous. Based on these characteristics, the reservoir stimulation technologies and fluid flow characteristics of carbonate reservoirs are briefly described in this study. The development methods and EOR technologies of carbonate reservoirs are systematically summarized, the relevant mechanisms are analyzed, and the application status of oil fields is catalogued. The challenges in the development of carbonate reservoirs are discussed, and future research directions are explored. In the current development processes of carbonate reservoirs, water flooding and gas flooding remain the primary means but are often prone to channeling problems. Chemical flooding is an effective method of tertiary oil recovery, but the harsh formation conditions require high-performance chemical agents. The application of emerging technologies can enhance the oil recovery efficiency and environmental friendliness to a certain extent, which is welcome in hard-to-recover areas such as heavy oil reservoirs, but the economic cost is often high. In future research on EOR technologies, flow field control and flow channel plugging will be the potential directions of traditional development methods, and the application of nanoparticles will revolutionize the chemical EOR methods. On the basis of diversified reservoir stimulation, combined with a variety of modern data processing schemes, multichannel EOR technologies are being developed to realize the systematic, intelligent, and cost-effective development of carbonate reservoirs. [ABSTRACT FROM AUTHOR]

Background: Peroral endoscopic myotomy (POEM) is a safe and effective approach for achalasia. However, the safety, feasibility, perioperative and long-term efficacy in treating geriatric patients has not been well evaluated.Methods: Data of 2367 patients diagnosed with achalasia and treated with POEM in the Endoscopy Center, Zhongshan Hospital, Fudan University from August 2010 to December 2017 were retrospectively reviewed. Last follow-up was in December 2018. Propensity score matching based on baseline characteristics was used to adjust for confounding. With a caliper of 0.01 in propensity scoring, 139 patients aged ≥ 65 years were matched at a 1:2 ratio with 275 patients aged < 65 years. Perioperative complications and long-term outcomes were compared between the two groups.Results: After propensity score matching, the two groups had similar baseline clinical characteristics and distribution of propensity scores. The mean age was 70.22 years in geriatric patients and 42.02 in younger patients. Technical failure occurred in one geriatric and one non-geriatric patients (p = 0.485). The procedural time in geriatric patients was similar to younger patients [50 (interquartile range (IQR) 36-76) vs. 50 (IQR 36-70) min, p = 0.398]. There were also no significant differences in major perioperative adverse events (2.88% vs. 2.18%, p = 0.663) and hospitalization length (median 3 vs. 3 days, p = 0.488). During a median follow-up period of 41 months (IQR 26-60), mean decrease in Eckardt score and pressure of the LES were 6.63 and 11.9 mmHg in geriatric patients, which were similar to the change in non-geriatric patients (6.49 and 11.6 mmHg, p = 0.652 and 0.872, respectively). Clinical reflux occurred in 23.53% geriatric patients and 21.59% non-geriatric patients (p = 0.724). 5-year success rate of 92.94% was achieved in geriatric patients and 92.61% in younger patients (log-rank p = 0.737).Conclusions: POEM is a safe and reliable treatment in geriatric achalasia patients with confirmed short-term and long-term efficacy compared with those in non-geriatric patients. [ABSTRACT FROM AUTHOR]

All known riboswitches use their aptamer to senese one metabolite signal and their expression platform to regulate gene expression. Here, we characterize a SAM-I riboswitch (SAM-IXcc) from the Xanthomonas campestris that regulates methionine synthesis via the met operon. In vitro and in vivo experiments show that SAM-IXcc controls the met operon primarily at the translational level in response to cellular S-adenosylmethionine (SAM) levels. Biochemical and genetic data demonstrate that SAM-IXcc expression platform not only can repress gene expression in response to SAM binding to SAM-IXcc aptamer but also can sense and bind uncharged initiator Met tRNA, resulting in the sequestering of the anti-Shine-Dalgarno (SD) sequence and freeing the SD for translation initiation. These findings identify a SAM-I riboswitch with a dual functioning expression platform that regulates methionine synthesis through a previously unrecognized mechanism and discover a natural tRNA-sensing RNA element. This SAM-I riboswitch appears to be highly conserved in Xanthomonas species. Riboswitches consist of an aptamer domain and expression platform, which senses a signal and regulates gene expression, respectively. Here the authors show that the expression platform of a SAM-I riboswitch from the Gram-negative bacteria can sense and bind uncharged an initiator Met tRNA to control the met operon. [ABSTRACT FROM AUTHOR]

Human serum globulin (GLB), which contains various antibodies in healthy human serum, is of great significance for clinical trials and disease diagnosis. In this study, the GLB in human serum was rapidly analyzed by near infrared (NIR) spectroscopy without chemical reagents. Optimal partner wavelength combination (OPWC) method was employed for selecting discrete information wavelength. For the OPWC, the redundant wavelengths were removed by repeated projection iteration based on binary linear regression, and the result converged to stable number of wavelengths. By the way, the convergence of algorithm was proved theoretically. Moving window partial least squares (MW-PLS) and Monte Carlo uninformative variable elimination PLS (MC-UVE-PLS) methods, which are two well-performed wavelength selection methods, were also performed for comparison. The optimal models were obtained by the three methods, and the corresponding root-mean-square error of cross validation and correlation coefficient of prediction (SECV, RP,CV) were 0.813 g L−1 and 0.978 with OPWC combined with PLS (OPWC-PLS), and 0.804 g L−1 and 0.979 with MW-PLS, and 1.153 g L−1 and 0.948 with MC-UVE-PLS, respectively. The OPWC-PLS and MW-PLS methods achieved almost the same good results. However, the OPWC only contained 28 wavelengths, so it had obvious lower model complexity. Thus it can be seen that the OPWC-PLS has great prediction performance for GLB and its algorithm is convergent and rapid. The results provide important technical support for the rapid detection of serum. [ABSTRACT FROM AUTHOR]

The roles and the underlying mechanisms of M1-type macrophages in angiogenesis and postmyocardial infarction (MI) cardiac repair have remained unclear. In this study, we investigated the role of M1-like macrophage-derived exosomes in a MI microenvironment. We found that the proinflammatory M1-like-type macrophages released an extensive array of proinflammatory exosomes (M1-Exos) after MI. M1-Exos exerted an anti-angiogenic effect and accelerated MI injury. They also exhibited highly expressed proinflammatory miRNAs, such as miR-155. miR-155 was transferred to endothelial cells (ECs), leading to the inhibition of angiogenesis and cardiac dysfunction by downregulating its novel target genes, including Rac family small GTPase 1 (RAC1), p21 (RAC1)-activated kinase 2 (PAK2), Sirtuin 1 (Sirt1), and protein kinase AMP-activated catalytic subunit alpha 2 (AMPKα2). M1-Exos depressed Sirt1/AMPKα2–endothelial nitric oxide synthase and RAC1–PAK2 signaling pathways by simultaneously targeting the five molecule nodes (genes), reduced the angiogenic ability of ECs, aggravated myocardial injury, and restrained cardiac healing. The elucidation of this mechanism provides novel insights into the functional significance of M1 macrophages and their derived exosomes on angiogenesis and cardiac repair. This mechanism can be used as a novel potential therapeutic approach for the prevention and treatment of MI. [ABSTRACT FROM AUTHOR]

Background: The endoscopic resection of gastrointestinal mesenchymal tumors (GIMTs) is widely accepted because of its minimal invasiveness. However, one major concern is the high rate of positive microscopic margins remaining following endoscopic resection, which was thought to be related to a higher risk of recurrence. This study aimed to determine whether positive margins affect the recurrence rate of gastric GIMTs and the factors associated with positive margins.Methods: Patients with gastric GIMTs were recruited retrospectively from January 2008 to December 2013. Clinical and pathological features, endoscopic procedure information, and follow-up data were collected and analyzed.Results: The study included 777 patients. All tumors were removed along with the pseudocapsule without macroscopic residual (ER0), and the median tumor size was 15.2 mm (range 3-100 mm). Pathological evaluation revealed 371(47.7%) GISTs. The rate of microscopic R1 resection rate was 47.0% (443/777). In a stepwise multivariate analysis, a significantly increased incidence of R1 resection was recorded for the GISTs (OR 11.13, 95% CI 3.00-41.37). In a subgroup analysis of GISTs, a univariate analysis revealed that EFTR achieved a higher rate of R0 resection (OR 0.56, 95% CI 0.31-1.00), but it was proven insignificant in a stepwise multivariate analysis. Local recurrence occurred in two patients (0.3%) during a mean follow-up time of 34.2 months. Differences in the recurrence rates between the R0 and R1 groups were statistically insignificant (P = 0.841).Conclusions: R1 resection for gastric GIMTs is not related to a higher recurrence rate than R0 resection, and ER0 resection is sufficient for gastric GIMTs. [ABSTRACT FROM AUTHOR]

Background: Endoscopic full-thickness resection (EFTR) provides a significant advancement to the treatment of gastrointestinal submucosal tumors (SMTs). However, technological challenges, particularly in the gastric fundus, hinder its wider application. Here, we investigated the efficacy of a simple traction method that used dental floss and a hemoclip (DFC) to facilitate EFTR.Methods: Between July 2014 and December 2016, we retrospectively reviewed data from all patients with SMTs in the gastric fundus originating from the muscularis propria layer that were treated by EFTR at Zhongshan Hospital of Fudan University. Baseline characteristics and clinical outcomes, including procedure time and complications rate, were compared between groups of patients receiving DFC-EFTR and conventional EFTR.Results: A total of 192 patients were included in our analysis (64 in the DFC-EFTR group and 128 in the conventional EFTR group). Baseline characteristics for the two groups were similar. The mean time for DFC-EFTR and conventional EFTR was 44.2 ± 24.4 and 54.2 ± 33.2 min, respectively (P = 0.034). Although no serious adverse events presented in any of our cases, post-EFTR electrocoagulation syndrome (PEECS), as a minor complication, was less frequent in the DFC-EFTR group (3.1% vs. 12.5%, P = 0.036). Univariate and multivariate analysis identified that DFC, when used in EFTR, played a significant role in reducing procedure time and the rate of PEECS. The mean procedure time was significantly shorter in the DFC-EFTR group for lesions over 1.0 cm (P = 0.005), when the lesions were located in the greater curvature of the gastric fundus (P = 0.025) or when the lesions presented with intraluminal growth (P = 0.032). Moreover, when EFTR was carried out by experts, the mean procedure time was 20.4% shorter in the DFC-EFTR group (P = 0.038).Conclusions: This study indicated that DFC-EFTR for SMTs in the gastric fundus resulted in a shorter procedure time and reduced the risk of PEECS, a minor complication. [ABSTRACT FROM AUTHOR]

Background: Gastric small submucosal tumors (SMTs) are becoming increasingly common. However, the fundus of stomach is regarded as a difficult area for endoscopic resection (ER). In this study, we investigated the efficacy, safety, and long-term outcomes of ER for small SMTs of the gastric fundus in a large series of patients, research that was previously lacking.Methods: 537 consecutive patients with SMTs no more than 20 mm in diameter, occurring in the gastric fundus and originating from the muscularis propria layer, which were treated with endoscopic submucosal excavation or endoscopic full-thickness resection (EFTR) were included in this retrospective study at Zhongshan Hospital of Fudan University from January 2013 to September 2016. Clinicopathological, endoscopic, and follow-up data were collected and analyzed.Results: En bloc resection was achieved in 100% of patients, and complete resection was achieved for 530 (98.7%) lesions. Although the total rate of complications was 9.3%, few serious adverse events occurred in only three (0.6%) patients, including major pneumoperitoneum, major hydrothorax, and bleeding. Unlike lager tumor sizes and longer procedure times, endoscopist experience had a positive impact on decreasing the likelihood of complications. Based on statistical analysis, tumors with greater size near the cardia, which were treated by EFTR, were the significant contributors to longer operative times. A median follow-up of 32 months was available, and all patients were free from local recurrence or distant metastasis during the study period.Conclusions: Although the gastric fundus presents technical difficulties, ER is effective for the resection of small gastric SMTs with a high complete resection rate and rare serious adverse events. [ABSTRACT FROM AUTHOR]

In this study, pentlandite was selectively separated from serpentine using magnetic coating technology by adjusting and optimizing pH, stirring speeds, magnetic field intensities, and dosages of sodium hexametaphosphate (SHMP) and sodium oleate (SO). A magnetic concentrate with Ni grade of 20.8% and Ni recovery of 80.5% was attained under the optimized operating conditions. Considering the above, the adsorption behaviors of SHMP and SO and the surface properties of minerals after the magnetic coating were studied by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM). The results show that magnetite was preferentially coated on the pentlandite surfaces and sparingly coated on the serpentine surfaces in the presence of SHMP and SO. Furthermore, calculations by Derjaguin-Landau-Verwey-Overbeek (DLVO) theory indicate that the preferential adsorption of magnetite on the pentlandite surfaces is due to the presence of a hydrophobic interaction between the magnetite and pentlandite, which is much stronger than the interaction between magnetite and serpentine. [ABSTRACT FROM AUTHOR]

Background: Peroral endoscopic myotomy (POEM) is a minimally invasive yet challenging procedure for achalasia. Additional technological innovations and improvements are important for simplifying the procedure.Methods: We report the successful use of a modified POEM procedure, which utilized a "Push and Pull" technique, on a patient with achalasia.Results: Our modifications resulted in a short operation time of only 35 min. No complications arose during or after the procedure, up to a follow-up period of 6 months, and symptoms were significantly and quickly improved.Conclusions: This modified procedure shortens operation time and lowers the difficulty of the operation, while leaving the safety and efficacy uncompromised. [ABSTRACT FROM AUTHOR]

Parvalbumin (PV) interneurons are critically involved in the cognitive processes. Based on prior investigations that environmental enrichment reverses impaired cognition after anesthetic exposure, we proposed that environmental enrichment protects PV interneurons and thereby improves sevoflurane-induced cognitive impairments. Six-day-old C57BL/6 male mice were exposed to 3 % sevoflurane or 30 % oxygen/air 2 h daily for 3 days from postnatal day 6 (P6) to P8. The mice were randomly allocated to an enriched environment for 2 h daily between P8 and P90 or a standard environment. Western blotting and immunofluorescence were used for determining PV expression in the prefrontal cortex and hippocampus. In another set of experiments, cognitive tests were assessed by the open field test (P41), Morris water maze test (P54-60), and fear conditioning tests (P42-43 and P89-90). Exposure of neonatal mice to sevoflurane resulted in a reduced freezing response in the contextual test at P43 but not P90. The PV expression in these mice was decreased at P9, P14, P28, and P42, but not at ≥P60. No colocalization of caspase-3 and 5-bromo-2-deoxyuridine or caspase-3 and PV was observed, suggesting that caspase-independent pathways may be involved in the mediation of sevoflurane-induced down-regulation of PV. The sevoflurane-exposed mice that were placed in an enriched environment exhibited normal behavior and had PV interneurons that did not differ from those in the control mice at P42-43. Neonatal sevoflurane exposure induces a reduced freezing response in the contextual test at P43 and developmental delays in PV interneurons in the prefrontal cortex and hippocampus. Placement of the sevoflurane-exposed mice in an enriched environment can prevent these abnormalities. [ABSTRACT FROM AUTHOR]

Background: Gastric schwannoma is not so recognized by clinicians as its counterparts. The efficacy of endoscopic resection has not been described yet. Our aim was to assess the efficacy and safety of endoscopic resection in the management of gastric schwannoma.Methods: Retrospective data were reviewed from January 2008 to December 2013 in our center. Fourteen patients who had endoscopic resection with the final pathology result of gastric schwannoma were included in the study.Results: Of the 14 patients, there were 12 females and two males. The median age was 59 years (range 32-83). Thirteen tumors (92.9 %) were from the muscularis propria and one located in the submucosa. Endoscopic en bloc resection was achieved in 12 patients (12/14, 85.7 %), including seven cases of endoscopic full-thickness resection (EFTR). The mean resected tumor size was 1.73 ± 1.10 cm (range 0.3-4.0 cm). In one case, endoscopic resection was suspended due to the limited experience of EFTR during the early period of the study. In another case, due to the difficult tumor location (gastric angle) and extraluminal growth pattern, the patient was referred to laparoscopic surgery. In the 12 successful endoscopic resection cases, during the median follow-up time of 4 years (range 17-77 months, one patient lost), no tumor residue, recurrence or metastasis was found.Conclusions: Endoscopic resection is safe and effective in treating gastric schwannoma with excellent long-term outcomes. However, it should be performed with caution because schwannoma is mainly located in the deep muscular layer, which leads to the full-thickness resection of gastric wall. [ABSTRACT FROM AUTHOR]

Tazarotene-induced gene 3 (TIG3) was first characterized in tazarotene-treated human keratinocytes and identified as a retinoic acid responder gene, an important mediator of antitumor effects by retinoids. In this study, we aim to investigate the inhibitory effect of TIG3 on the growth of liver cancer and explore its underlying mechanism. Human hepatocellular carcinoma (HCC) Hep3B cells were transfected with plasmid GV141 carrying full-length TIG3 complementary DNA (cDNA). The effects of TIG3 on cell proliferation, apoptosis, and migration were determined in vitro. The suppressor effect of TIG3 on tumor growth was evaluated in vivo in a nude mouse HCC model. We observed that TIG3 expression is decreased in the Hep3B cell line as well as primary HCC tumors, and TIG3 expression inversely correlates with Ki-67 expression. Overexpression of TIG3 suppresses tumor growth in HCC both in vitro and in vivo via ERK1/2 inhibition by promoting apoptosis and inhibiting proliferation and migration. These findings identify TIG3 as an attractive therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

Background: An increasing number of studies have been conducted on the use of endoscopic ultrasound (EUS)-guided needle sampling for upper gastrointestinal subepithelial lesions (SEL). However, reported diagnostic efficacy varies greatly.Objective: To summarize up current evidences on the diagnostic efficacy of EUS-guided needle sampling for upper GI SEL.Method: A reproducible strategy was used to search four databases. Search results were evaluated for eligibility, and the quality of eligible studies was assessed by QUADAS-2. Pooled efficacy of EUS-guided needle sampling in upper GI SEL was calculated. Procedure-related complications, diagnostic errors, and independent factors related to a higher success rate were also recorded and analyzed.Results: Seventeen studies, comprising 978 attempts of EUS-guided needle sampling, were included in a meta-analysis. Pooled diagnostic rate of EUS-guided needle sampling was 59.9 %, with a heterogeneity I (2) of 55.2 %. Subgroup analysis showed no difference in diagnostic rate among fine needle aspiration (FNA), trucut needle biopsy (TCB), and fine needle biopsy (FNB), or among 19-, 22-, and 25-G needles. Subgroup analysis and meta-regression suggested that the cell block method might be correlated with a higher diagnostic rate. Few severe complications were reported. Diagnosis errors were rare.Conclusion: EUS-guided needle sampling is a safe, but only moderately effective method for pathology diagnosis of upper GI SEL. Choice of FNA/TCB/FNB, or 19 G/22 G/25 G does not seem to alter the overall diagnostic rate. [ABSTRACT FROM AUTHOR]

Backgroud: The efficacy and safety of self-expandable metallic stents (SEMSs) as a bridge for patients with acute malignant colorectal obstructions (AMCOs) are still controversial. We conducted this study to evaluate the outcomes of patients with AMCOs treated by different strategies. Methods: From January 2010 to March 2014, a total of 171 patients with AMCOs from Zhongshan Hospital were retrospectively enrolled in this study. One hundred twenty patients successfully received stent placement followed by one-stage laparoscopic or open resection in the stent group, and 51 patients received emergency operations in the emergency group. Results: The operation duration and postoperative hospital stay were significantly shorter in the stent group (114.51 ± 28.65 vs. 160.39 ± 58.94 min, P < 0.001; 8.00 ± 3.97 vs. 12.59 ± 9.07 days, P = 0.001). The stent group also had significantly reduced intraoperative blood loss and the incidence of postoperative complications compared with the emergency group (61.00 ± 43.70 vs. 121.18 ± 85.90 ml, P < 0.001; 16.7 vs. 37.3 %, P = 0.003). Kaplan-Meier survival curves showed that the median survival time in the stent group was significantly longer than that in the emergency group (53 vs. 41 months, P = 0.034). In subgroup analysis of stent group, the stent laparoscopy group had significantly decreased postoperative complications ( P = 0.025), and similar long-term survival ( P = 0.81). Conclusions: Stent placement as a bridge to surgery is a safe and feasible procedure and provides significant advantages in terms of short-term outcomes and favorable prognoses for patients with AMCOs. Laparoscopic surgery could be considered as an optimal treatment after stent placement. [ABSTRACT FROM AUTHOR]

General anesthetics given to immature rodents cause delayed neurobehavioral abnormalities via incompletely understood mechanisms. DNA methylation, one of the epigenetic modifications, is essential for the modulation of hippocampal synaptic plasticity through regulating the related genes. Therefore, we investigated whether abnormalities in the hippocampal DNA methylation of synaptic plasticity-related genes are involved in neonatal sevoflurane exposure-induced cognitive impairments in rats. Male Sprague-Dawley rats were exposed to 3 % sevoflurane or 30 % oxygen/air for 2 h daily from postnatal day 7 (P7) to P9 and were treated with DNA methyltransferases (DNMTs) inhibitor 5-aza-2-deoxycytidine (5-AZA) or vehicle 1 h before the first sevoflurane exposure on P7. The rats were euthanized 1, 6, 24 h, and 30 days after the last sevoflurane exposure, and the brain tissues were harvested for biochemical analysis. Cognitive functions were evaluated by the open field, fear conditioning, and Morris water maze (MWM) tests on P39, P41-43, and P50-57, respectively. In the present study, repeated neonatal sevoflurane exposure resulted in hippocampus-dependent cognitive impairments as assessed by fear conditioning and MWM tests. The cognitive impairments were associated with the increased DNMTs and hypermethylation of brain-derived neurotrophic factor (BDNF) and Reelin genes, and subsequent down-regulation of BDNF and Reelin genes, which finally led to the decrease of dendritic spines in the hippocampal pyramidal neurons in adolescent rats. Notably, pretreatment with 5-AZA reversed these sevoflurane-induced abnormalities. In conclusion, our results suggest that hypermethylation of hippocampal BDNF and Reelin is involved in neonatal sevoflurane exposure-induced cognitive impairments. [ABSTRACT FROM AUTHOR]

Background: Submucosal tunneling endoscopic resection (STER) can be adequately adopted as an effective treatment for submucosal tumors (SMTs) originating from the muscularis propria (MP) layer at the esophagus and cardia. However, it has been seldom used for gastric SMTs. Our purpose was to evaluate the clinical impact of STER for gastric SMTs arising from the MP layer.Methods: Thirty-two patients with gastric SMTs from the MP layer were retrospectively included. The main outcome measurements were complete resection rate, adverse events, local recurrence, and distant metastases during follow-up.Results: Of the 32 lesions, 12 were located in the gastric corpus close to the cardia, 3 in the gastric fundus close to the cardia, 6 in the lesser curvature of the gastric corpus, and 11 in the greater curvature of the gastric antrum. STER was successfully performed in all patients with en bloc resection of tumors. The mean tumor size was 2.3 cm (range 1.0-5.0 cm). The complete resection rate was 100%. The operation time ranged from 25 to 125 min (mean 51.8 min). All complications related to STER were successfully managed with conservative treatments. Local recurrence or distant metastasis did not occur during a follow-up period of 6-32 months.Conclusion: STER is a safe and effective therapeutic strategy for eligible gastric SMTs originating from the MP layer. Submucosal tunneling in the stomach may be more challenging than that in the esophagus, but does not increase procedure-related adverse events or prevent successful STER for eligible gastric SMTs. [ABSTRACT FROM AUTHOR]

Background: The sigmoid-shaped esophagus is considered to be the advanced stage of achalasia, in which the esophageal lumen is significantly dilated, swerved, and rotated. In consideration of the efficacy of peroral endoscopic myotomy (POEM) for early achalasia, it may also offer another option for the treatment of advanced achalasia with sigmoid-shaped esophagus. Our purpose was to evaluate the feasibility and long-term efficacy of POEM for patients with sigmoid-type achalasia. Methods: 32 consecutive patients with sigmoid-type achalasia (S1 type in 29 patients and S2 type in 3 patients) were prospectively included. Primary outcome was symptom relief during follow-up, defined as an Eckardt score ≤3. Secondary outcomes were procedure-related adverse events, the resting lower esophageal sphincter (LES) pressure, clinical reflux complications, and procedure-related parameters. Results: All cases received POEM successfully. The mean operation time was 63.7 min (range 22-130 min). No serious complications related to POEM were encountered. During a mean follow-up period of 30.0 months (range 24-44 months), treatment success was achieved e in 96.8 % of cases (mean score pre- vs. post-treatment 7.8 vs. 1.4; P < 0.001). Mean LES pressure also decreased from a mean of 37.9 to 12.9 mmHg after POEM ( P < 0.001). One patient experienced only partial symptom relief and additional balloon dilations were carried out to relief the symptoms twice. The overall clinical reflux complication rate of POEM for sigmoid-type achalasia was 25.8 %. Conclusion: The 2-year outcomes of POEM for advanced achalasia with sigmoid-shaped esophagus were excellent, resulting in long-term symptom relief in over 96 % cases and without serious complications. The morphological changes of esophagus may make subsequent endoscopic tunneling more challenging and time-consuming, but do not prevent successful POEM. [ABSTRACT FROM AUTHOR]

Baicalin, a flavonoid monomer derived from Scutellaria baicalensis called Huangqin in mandarin, is the main active ingredient contributing to S. baicalensis' efficacy. It is known in China that baicalin has potential therapeutic effects on inflammatory diseases. However, its anti-inflammatory mechanism has still not been fully interpreted. We aim to investigate the anti-inflammatory effect of baicalin on lipopolysaccharide (LPS)-induced inflammation in HBE16 airway epithelial cells and also to explore the underlying signaling mechanisms. The anti-inflammatory action of baicalin was evaluated in human airway epithelial cells HBE16 treated with LPS. Airway epithelial cells HBE16 were pretreated with a range of concentrations of baicalin for 30 min and then stimulated with 10 μg/ml LPS. The secretions of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) in cell culture supernatants were quantified by enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expressions of IL-6, IL-8, and TNF-α were tested by quantitative real-time polymerase chain reaction (real-time RT-PCR). Furthermore, Western blotting was used to determine whether the signaling pathway NF-κB was involved in the anti-inflammatory action of baicalin. The inflammatory cell model was successfully built with 10 μg/ml LPS for 24 h in our in vitro experiments. Both the secretions and the mRNA expressions of IL-6, IL-8, and TNF-α were significantly inhibited by baicalin. Moreover, the expression levels of phospho-IKKα/β and phospho-NF-κB p65 were downregulated, and the phospho-IκB-α level was upregulated by baicalin. These findings suggest that the anti-inflammatory properties of baicalin may be resulted from the inhibition of IL-6, IL-8, and TNF-α expression via preventing signaling NF-κB pathway in HBE16 airway epithelial cells. In addition, this study provides evidence to understand the therapeutic effects of baicalin on inflammatory diseases in clinical practice. [ABSTRACT FROM AUTHOR]

Aim:The receptor for advanced glycation end-products (RAGE) plays an important role in development of atherosclerosis, and C-reactive protein (CRP) has been found to stimulate its expression in endothelial cells. In this study we investigated how CRP regulated the expression of RAGE in human coronary artery endothelial cells (HCAECs).Methods:HCAECs were treated in vitro with CRP (50 μg/mL) in combination with a variety of inhibitors. ROS generation was determined by immunocytochemistry and flow cytometry. The RAGE expression and phosphorylation of relevant signaling proteins were measured using Western blot analyses.Results:CRP stimulated the expression of RAGE in the cells, accompanied by markedly increased ROS generation, phosphorylation of ERK1/2 and NF-κB p65, as well as translocation of NF-κB p65 to the nuclei. CRP also stimulated phosphorylation of JNK and p38 MAPK. Pretreatment of the cells with the ROS scavenger N-acetyl-L-cysteine, ERK inhibitor PD98059 or NF-κB inhibitor PDTC blocked CRP-stimulated RAGE expression, but pretreatment with the NADPH oxidase inhibitor DPI, JNK inhibitor SP600125 or p38 MAPK inhibitor SB203580 did not significantly alter CRP-stimulated RAGE expression.Conclusion:CRP stimulates RAGE expression in HCAECs in vitro via ROS generation and activation of the ERK/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Coatings containing Fe-Si particles were electrodeposited on 3.0wt% Si steel sheets under magnetic fields. The effects of magnetic flux density (MFD), electrode arrangement and current density on the surface morphology, the silicon content in the coatings and the cathode current efficiency were investigated. When a magnetic field was applied parallel to the current and when the MFD was less than 0.5 T, numerous needle-like structures appeared on the coating surface. With increasing MFD, the needle-like structures weakened and were transformed into dome-shaped structures. Meanwhile, compared to results obtained in the absence of a magnetic field, the silicon content in the coatings significantly increased as the MFD was increased for all of the samples obtained using a vertical electrode system. However, in the case of an aclinic electrode system, the silicon content decreased. Furthermore, the cathode current efficiency was considerably diminished when a magnetic field was applied. A possible mechanism for these phenomena was discussed. [ABSTRACT FROM AUTHOR]

The main cause of death in colorectal carcinoma (CRC) patients is tumor metastasis; however, the underlying molecular mechanisms are largely unknown. In the present study, a novel metastasis-related gene, fibrinogen-like protein 2 (FGL2), was characterized for its role in CRC metastasis and underlying molecular mechanisms. The clinical significance of FGL2 was investigated using tissue microarray analysis of samples from 82 patients with CRC. The molecular effects of FGL2 in CRC cells were determined using RNA interference and ectopic expression of FGL2. The overexpression of FGL2 was examined by immunohistochemistry in 82 CRC patients, and it was determined to be an independent predictor of overall survival ( P < 0.05). The depletion of FGL2 expression inhibited tumor progression and epithelial-to-mesenchymal transition (EMT) in vitro and in vivo, while ectopic overexpression of FGL2 enhanced cell invasion and induced EMT in vitro. Our results suggest that FGL2 plays an important oncogenic role in CRC aggressiveness by inducing EMT, and FGL2 could be employed as a novel prognostic marker and effective therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

Background: The esophagogastric junction (EGJ) is a difficult location for endoscopic resection due to its narrow lumen and sharp angle. Potential increased risks of perforation and mediastinal infection exist, especially for submucosal tumors (SMTs) originating from the muscularis propria (MP) layer. We previously demonstrated the safety and efficacy of submucosal tunneling endoscopic resection (STER) for upper gastrointestinal SMTs, but the feasibility of STER for the removal of SMTs at the EGJ requires systematic investigation. The aim of the investigation was to evaluate the clinical impact of STER on the removal of SMTs at the EGJ. Methods: A prospective study was carried out which included a consecutive cohort of 57 patients who underwent STER for 57 SMTs of the EGJ originating from the MP layer between July 2010 and August 2012 in a single academic medical center. Adverse events, en bloc resection rate, and local recurrence were evaluated. Results: The average maximum diameter of the lesions was 21.5 mm (range 6-35 mm). The en bloc resection rate was 100 % (57/57). No delayed hemorrhage or severe adverse events occurred in any of the 57 patients following STER. No local recurrence and distant metastasis occurred during 24 months' follow-up. Less subcutaneous emphysema and pneumomediastinum absorption time ( p = 0.005) occurred with CO versus air insufflations. Conclusions: Our study showed that STER was safe and effective, provided accurate histopathologic evaluation, and was curative for SMTs of the deep MP layers at the EGJ. CO gas insufflation is recommended. [ABSTRACT FROM AUTHOR]

Emerging data have shown that microRNAs (miRNAs) have important functions in the processes of cardiac hypertrophy and heart failure that occur during the postnatal period. Cardiac overexpression of miR-195 results in pathological cardiac growth and heart failure in transgenic mice. In the present study, we analyzed the roles of miR-195 in cardiomyocyte hypertrophy and found that miR-195 was greatly upregulated during isoprenaline-induced cardiomyocyte hypertrophy. By using mRNA microarray and molecular approach, we identified a novel putative target of miR-195 called high-mobility group A1 (HMGA1). Total mRNA microarray showed that HMGA1 was downregulated in primary cardiomyocytes that overexpressed miR-195. Using luciferase activity assay, we demonstrated that miR-195 interacts with the 3′-untranslated region of HMGA1 mRNA. Moreover, we showed that miR-195 in primary cardiomyocytes downregulates the expression of HMGA1 at the protein level. Taken together, our data demonstrated that miR-195 can negatively regulate a new target, HMGA1, which is involved in cardiomyocyte hypertrophy. [ABSTRACT FROM AUTHOR]

Protein-protein interactions (PPIs) play crucial roles in diverse cellular processes. There are different types of PPIs based on the composition, affinity and whether the association is permanent or transient. Analyzing the diversity of PPIs at the atomic level is crucial for uncovering the key features governing the interactions involved in PPI. A systematic physico-chemical and conformational studies were implemented on interfaces involved in different PPIs, including crystal packing, weak transient heterodimers, weak transient homodimers, strong transient heterodimers and homodimers. The comparative analysis shows that the interfaces tend to be larger, less planar, and more tightly packed with the increase of the interaction strength. Meanwhile the strong interactions undergo greater conformational changes than the weak ones involving main chains as well as side chains. Finally, using 18 features derived from our analysis, we developed a support vector regression model to predict the binding affinity with a promising result, which further demonstrate the reliability of our studies. We believe this study will provide great help in more thorough understanding the mechanism of diverse PPIs. [ABSTRACT FROM AUTHOR]

Background: Peroral endoscopic myotomy (POEM) has recently been introduced as a promising alternative to laparoscopic Heller myotomy for idiopathic achalasia. Several proposed technical modifications are yet to be tested in randomized trials. Objective: The objective of our study was to evaluate efficacy and safety of water-jet (WJ) assisted POEM versus the conventional (C) technique. The clinical trial registration number is NCT01742494. Methods: A prospective randomized trial was carried out in Zhongshan Hospital, Fudan University (Shanghai, China), in 100 consenting achalasia patients between August 2011 and April 2012. Patients eligible for POEM were randomized to use of either the HybridKnife (WJ group) or the conventional technique using injection and triangle tip knife interchangeably (C group). Results: A total of 100 patients with comparable characteristics between groups were included. Procedure time was significantly shorter for the WJ group (22.9 ± 6.7 vs. 35.9 ± 11.7 min; p < 0.0001), mostly due to less replacement of accessories (2.0 ± 2.4 vs. 19.2 ± 7.6; p < 0.0001). Injection volume was larger in the WJ group (45.3 ± 10.2 vs. 35.2 ± 9.5 ml; p < 0.0001) and was associated with fewer minor bleeding episodes (3.6 ± 1.8 vs. 6.8 ± 5.2; p < 0.0001). No severe complications occurred; one case of cutaneous emphysema occurred in the WJ group, and four cases occurred in the C group ( p = 0.17), three cases of pneumonia were encountered in the C group and none in the WJ group ( p = 0.24). Treatment success (Eckardt score ≤3) was achieved in 96.5 % of patients, with no significant differences between groups. Conclusions: The use of the HybridKnife leads to a significant decrease in POEM procedure time and facilitates reinjection, possibly contributing to a lower rate of minor intra-procedural bleeding. [ABSTRACT FROM AUTHOR]

Emerging evidence demonstrates that high plasma C-reactive protein (CRP) levels or low plasma insulin-like growth factor 1 (IGF-1) concentrations may be separately associated with the increased risk of coronary artery disease or myocardial infarction. Interestingly, animal model studies and epidemiological investigations indicate that circulating IGF-1 and CRP levels have an inverse correlation. The present study aims to evaluate if IGF-1 can directly oppose the effects of CRP on endothelial cell (EC) activation. We found that IGF-1 rescues endothelial nitric oxide synthase activity and decreases the release of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 from ECs. We also showed that IGF-1 antagonizes the effects of CRP by activating the PI3K/Akt pathway and suppressing the JNK/c-Jun and MAPK p38/ATF2 signaling pathways, rather than inhibiting ERK1/2 activity. These findings provide evidence of the physiopathological mechanisms of endothelial activation and novel insights into the protective properties of IGF-1. [ABSTRACT FROM AUTHOR]

Background: Increasing colonoscopy use increases the incidence of iatrogenic colon perforation. Operative management of iatrogenic colonoscopic perforation is diverse. This study retrospectively reviewed our experiences in treating diagnostic colonoscopy-associated bowel perforation by laparoscopic direct suturing. Methods: A total of 89,014 patients underwent diagnostic colonoscopy at our institution during the past 6 years. We identified 17 iatrogenic perforations (0.019 %) that were all managed by laparoscopic direct suturing. Results: Perforation patients included 11 men and 6 women (mean age 60 ± 18 years). Sixteen patients (94 %) had severe comorbidities or previous abdominal surgery. Perforations were noticed by the endoscopist during the procedure in 13 cases (76 %) while the remaining 4 cases (24 %) were diagnosed within 24 h after colonoscopy. The estimated mean longitudinal perforation length was 4.4 ± 2.1 cm. Mean operation time was 2.3 ± 0.6 h, without significant blood loss or other severe complication. The mean time to bowel function return was 3.4 ± 1.2 days, the mean time to initial oral intake was 3.9 ± 2.0 days and the mean hospitalization duration was 6.8 ± 4.2 days. Conclusions: Diagnostic colonoscopic perforation occurred in less than 2/10,000 patients when colonoscopy was performed by experienced operators in our endoscopy center. Most of the perforation patients had severe comorbidities, to which the surgeon should pay close attention during colonoscopy. Laparoscopic primary suture of colon perforations caused by diagnostic colonoscopy is a safe and feasible repair method. Further efforts will definitively assess the feasibility of routinely using laparoscopic direct suture to repair colon perforations. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) is a significant contributor to atherosclerosis and a powerful predictor of cardiovascular risk. The role of CRP in endothelial cell (EC) activation has been extensively investigated, but the underlying mechanisms have not been fully elucidated. The effect of glycogen synthase kinase-3β (GSK-3β) on CRP-induced EC activation was evaluated in this study. We observed that CRP decreased endothelial nitric oxide synthase (eNOS) activity during EC activation. CRP also activated GSK-3β by dephosphorylating its Ser9 level and reducing β-catenin protein expression in a time-dependent manner. We also found that the GSK-3β inhibitors TDZD-8 and SB415286 partially restored eNOS activity and suppressed the release of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 from ECs. These data provide new evidence for the involvement of GSK-3β in EC activation. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the clinicopathological features of specific subtypes of laterally spreading tumor (LST) and assessed the outcome of endoscopic submucosal dissection (ESD) based upon subdifferentiation status. Methods: A total of 137 LSTs were present in 135 patients; 96 were granular and 41 exhibited a nongranular pattern. Granular LSTs, subdivided into homogeneous and nodular mixed, and nongranular LSTs, subdivided into flat-elevated and pseudodepressed, were retrospectively evaluated with respect to clinicopathological features and results of ESD (en bloc R0 curative resection, procedure time, complication, and recurrence rate) according to specific subtype. Results: The distribution of high-grade intraepithelial neoplasia and submucosal carcinomas was more prominent among granular nodular mixed tumors than among granular homogeneous tumors ( P = 0.007), whereas there was no significant difference between nongranular pseudodepressed tumors and flat-elevated tumors. The frequency of en bloc R0 curative resection did not differ significantly among specific subtypes. For nodular mixed and pseudodepressed lesions, the median tumor size was significantly larger ( P < 0.001 for each) and mean procedure time was also longer ( P < 0.05 for each) than for the other two subtypes. All complications, which included three perforations, five episodes of postoperative bleeding, and one recurrence, occurred in granular nodular mixed and nongranular pseudodepressed tumors. Conclusion: The risk of cancer varies with the subtypes of LSTs. ESD is an effective treatment for LSTs, however ESD is more technically demanding and carries more complications in pseudodepressed and granular mixed subtypes. [ABSTRACT FROM AUTHOR]

Background: Insulin antibody (IAb) may be produced in patients receiving long-term, animal-derived insulin, leading to insulin resistance or hypoglycemia. There have been very few reports of hypoglycemia caused by IAb in patients taking recombinant human insulin. Case Report: We report the case of an 82-year-old male patient with type 2 diabetes mellitus who suffered repeated episodes of severe hypoglycemia-related symptoms (including coma) prior to admission. The patient had been taking Novolin 30R, a premixed human insulin. The patient's IAb level was markedly elevated, and hypoglycemia caused by recombinant human insulin treatment-induced IAb production was diagnosed. Acarbose and metformin were prescribed, and the patient recovered uneventfully. The patient ceased taking these medications, and he was subsequently treated with recombinant human insulin to combat hyperglycemia. This was followed by reoccurrence of hypoglycemic coma. The patient was advised to avoid taking recombinant human insulin for the rest of his life and to control hyperglycemia with acarbose and metformin. Conclusions: Although rare, hypoglycemia caused by recombinant human insulin-induced IAb production should be considered in patients with type 2 diabetes who experience repeated episodes of hypoglycemia. [ABSTRACT FROM AUTHOR]

The genic multiple-allele inherited male-sterile gene Ms in Chinese cabbage ( Brassica rapa L.) was identified as a spontaneous mutation. Applying this gene to hybrid seed production, several B. rapa cultivars have been successfully bred in China. A BC1 population (244 plants) was constructed for mapping the Ms gene. Screening 268 simple sequence repeat (SSR) markers which cover the entire genome of Chinese cabbage was performed with bulked segregant analysis (BSA). On the basis of linkage analysis, the Ms gene was located on linkage group R07. In addition, through the amplified fragment length polymorphism (AFLP) and the sequence-characterized amplified region (SCAR) techniques combining BSA, two SCAR markers which were converted from corresponding AFLP markers flanked the Ms gene. Finally, a genetic map of the Ms gene was constructed covering a total interval of 9.0 cM. Two SCAR markers, syau_scr01 and syau_scr04, flanked the Ms gene at distances of 0.8 and 2.5 cM, respectively. All the SSR markers (cnu_m273, cnu_m030, cnu_m295, and syau_m13) were mapped on the same side of the gene as syau_scr04, the nearest one of which, syau_m13, was mapped at a distance of 3.3 cM. These SSR and SCAR markers may be useful in marker-assisted selection and map-based cloning. [ABSTRACT FROM AUTHOR]

Abstract  Metastasis of lung cancer to the penis is very rare; it causes various clinical symptoms seriously affecting the quality of life. Early recognition and appropriate management will likely enhance survival in these patients. Here, we report a case of penile metastasis secondary to pulmonary carcinoma along with a review of the literature. One case of penile metastasis secondary to pulmonary carcinoma was detected in a 51-year-old patient who was admitted to the First Affiliated Hospital of Sun Yat-Sen University with persistent cough along with swelling of the perineum and penis. The clinical features, diagnosis, and treatment of this disease along with a relevant literature are reviewed and discussed. A MEDLINE search was performed to identify similar reports in the literature. CT scan revealed lung mass, and a glans penis ulcer and enlargement of inguinal lymph nodes was discovered upon physical examination. CT-guided percutaneous puncture of the lung mass revealed adenocarcinoma of lung, and biopsies of the glans penis ulcer and inguinal lymph nodes confirmed metastatic adenocarcinoma. The patients received chemotherapy and died of acute pulmonary embolism in less than 2 months. Metastasis of lung cancer to the penis is extremely rare. It presents an advanced form of lung cancer, and thus survival is extremely short. Although treatment of penile metastasis is almost always palliative, early recognition may enhance survival for these patients. [ABSTRACT FROM AUTHOR]

Beclin 1, a mammalian autophagy protein that has been implicated in development, tumour suppression, neurodegeneration and cell death, exists in a complex with Vps34, the class III phosphatidylinositol-3-kinase (PI(3)K) that mediates multiple vesicle-trafficking processes including endocytosis and autophagy. However, the precise role of the Beclin 1–Vps34 complex in autophagy regulation remains to be elucidated. Combining mouse genetics and biochemistry, we have identified a large in vivo Beclin 1 complex containing the known proteins Vps34, p150/Vps15 and UVRAG, as well as two newly identified proteins, Atg14L (yeast Atg14-like) and Rubicon (RUN domain and cysteine-rich domain containing, Beclin 1-interacting protein). Characterization of the new proteins revealed that Atg14L enhances Vps34 lipid kinase activity and upregulates autophagy, whereas Rubicon reduces Vps34 activity and downregulates autophagy. We show that Beclin 1 and Atg14L synergistically promote the formation of double-membraned organelles that are associated with Atg5 and Atg12, whereas forced expression of Rubicon results in aberrant late endosomal/lysosomal structures and impaired autophagosome maturation. We hypothesize that by forming distinct protein complexes, Beclin 1 and its binding proteins orchestrate the precise function of the class III PI(3)K in regulating autophagy at multiple steps. [ABSTRACT FROM AUTHOR]