Computer-Aided Image Enhanced Endoscopy Automated System to Boost Polyp and Adenoma Detection Accuracy.

Colonoscopy is the gold standard to detect colon polyps prematurely. Early detection, characterization and resection of polyps decrease colon cancer incidence. Colon polyp missing rate remains high despite novel methods development. Narrowed-band imaging (NBI) is one of the image enhance techniques used to boost polyp detection and characterization, which uses special filters to enhance the contrast of the mucosa surface and vascular pattern of the polyp. However, the single-button-activated system is not convenient for a full-time colonoscopy operation. We selected three methods to simulate the NBI system: Color Transfer with Mean Shift (CTMS), Multi-scale Retinex with Color Restoration (MSRCR), and Gamma and Sigmoid Conversions (GSC). The results show that the classification accuracy using the original images is the lowest. All color transfer methods outperform the original images approach. Our results verified that the color transfer has a positive impact on the polyp identification and classification task. Combined analysis results of the mAP and the accuracy show an excellent performance of the MSRCR method.

Polyp detection and false-positive rates by computer-aided analysis of withdrawal-phase videos of colonoscopy of the right-sided colon segment in a randomized controlled trial comparing water exchange and air insufflation.

BACKGROUND AND AIMS: Water exchange (WE) improves lesion detection but misses polyps because of human limitations. Computer-aided detection (CADe) identifies additional polyps overlooked by the colonoscopist. Additional polyp detection rate (APDR) is the proportion of patients with at least 1 additional polyp detected by CADe. The number of false positives (because of feces and air bubble) per colonoscopy (FPPC) is a major CADe limitation, which might be reduced by salvage cleaning with WE. We compared the APDR and FPPC by CADe between videos of WE and air insufflation in the right-sided colon. METHODS: CADe used a convolutional neural network with transfer learning. We edited and coded withdrawal-phase videos in a randomized controlled trial that compared right-sided colon findings between air insufflation and WE. Two experienced blinded endoscopists analyzed the CADe-overlaid videos and identified additional polyps by consensus. An artifact triggered by CADe but not considered a polyp by the reviewers was defined as a false positive. The primary outcome was APDR. RESULTS: Two hundred forty-five coded videos of colonoscopies inserted with WE (n = 123) and air insufflation (n = 122) methods were analyzed. The APDR in the WE group was significantly higher (37 [30.1%] vs 15 [12.3%], P = .001). The mean [standard deviation] FPPC related to feces (1.78 [1.67] vs 2.09 [2.09], P = .007) and bubbles (.53 [.89] vs 1.25 [2.45], P = .001) in the WE group were significantly lower. CONCLUSIONS: CADe showed significantly higher APDR and lower number of FPPC related to feces and bubbles in the WE group. The results support the hypothesis that the strengths of CADe and WE complement the weaknesses of each other in optimizing polyp detection.

Computer-Aided Colon Polyp Detection on High Resolution Colonoscopy Using Transfer Learning Techniques.

Colonoscopies reduce the incidence of colorectal cancer through early recognition and resecting of the colon polyps. However, the colon polyp miss detection rate is as high as 26% in conventional colonoscopy. The search for methods to decrease the polyp miss rate is nowadays a paramount task. A number of algorithms or systems have been developed to enhance polyp detection, but few are suitable for real-time detection or classification due to their limited computational ability. Recent studies indicate that the automated colon polyp detection system is developing at an astonishing speed. Real-time detection with classification is still a yet to be explored field. Newer image pattern recognition algorithms with convolutional neuro-network (CNN) transfer learning has shed light on this topic. We proposed a study using real-time colonoscopies with the CNN transfer learning approach. Several multi-class classifiers were trained and mAP ranged from 38% to 49%. Based on an Inception v2 model, a detector adopting a Faster R-CNN was trained. The mAP of the detector was 77%, which was an improvement of 35% compared to the same type of multi-class classifier. Therefore, our results indicated that the polyp detection model could attain a high accuracy, but the polyp type classification still leaves room for improvement.

Computer-Aided Detection False Positives in Colonoscopy.

Randomized control trials and meta-analyses comparing colonoscopies with and without computer-aided detection (CADe) assistance showed significant increases in adenoma detection rates (ADRs) with CADe. A major limitation of CADe is its false positives (FPs), ranked 3rd in importance among 59 research questions in a modified Delphi consensus review. The definition of FPs varies. One commonly used definition defines an FP as an activation of the CADe system, irrespective of the number of frames or duration of time, not due to any polypoid or nonpolypoid lesions. Although only 0.07 to 0.2 FPs were observed per colonoscopy, video analysis studies using FPs as the primary outcome showed much higher numbers of 26 to 27 per colonoscopy. Most FPs were of short duration (91% < 0.5 s). A higher number of FPs was also associated with suboptimal bowel preparation. The appearance of FPs can lead to user fatigue. The polypectomy of FPs results in increased procedure time and added use of resources. Re-training the CADe algorithms is one way to reduce FPs but is not practical in the clinical setting during colonoscopy. Water exchange (WE) is an emerging method that the colonoscopist can use to provide salvage cleaning during insertion. We discuss the potential of WE for reducing FPs as well as the augmentation of ADRs through CADe.

[Analysis on formula of Mongolian medicine for prevention of COVID-19].

The epidemic situation of coronavirus disease 2019(COVID-19) is developing rapidly in the world, and the influence is serious. In this study, the prescription of Mongolian medicine to prevent new type of COVID-19 was investigated. Based on the second edition and the third edition of COVID-19 Mongolian Medicine Prevention and Treatment Guidance Program issued by the Inner Mongolia Autonomous Region Health Commission, using Excel 2007, SPSS Modeler 18, SPSS Statistics 25, Cytoscape 3.7.1 statistical software as a tool, the association rules analysis and cluster analysis of Mongolian medicine included in the standard were carried out. Among the 45 prophylactic prescriptions included in the standard, a total of 34 high-frequency drugs using frequency ≥5 were used, of which Carthami Flos(21 times, 4.46%), Chebulae Fructus(20 times, 4.26%), Moschus(13 times, 2.77%), Myristicae Semen(12 times, 2.55%), Santali Albi Lignum(12 times, 2.55%), and Bovis Calculus(12 times, 2.55%) were the most common. The main drugs for the prevention of COVID-19 were Liang(13 times, 38.23%), Wen(9 times, 26.47%), the flavor was Ku(20 times, 34.48%), Xin(13 times, 22.41%), Gan(11 times, 18.97%), the most used drugs treating hot evil(99 times, 32.46%), treatment of "Heyi" drugs(51 times, 16.72%), treatment of "Badagan" drugs(40 times, 13.11%), treatment of "sticky" drugs(37 times, 12.13%), and a cough, eliminating phlegm and antiasthmatic(31 times, 10.16%), the association rule analysis found that the highest association intensity of the drug pair combination of 11. Clustering analysis using the cluster analysis of inter-group join method found a total of 8 categories. In this study, 45 prescriptions of Mongolian medicine for the prevention of COVID-19 were collec-ted and further analyzed, hoping to provide new ideas for clinical diagnosis and treatment.

A Location Privacy Attack Based on the Location Sharing Mechanism with Erroneous Distance in Geosocial Networks.

Geographical social networks (GSN) is an emerging research area. For example, Foursquare, Yelp, and WeChat are all well-known service providers in this field. These applications are also known as location-based services (LBS). Previous studies have suggested that these location-based services may expose user location information. In order to ensure the privacy of the user's location data, the service provider may provide corresponding protection mechanisms for its applications, including spatial cloaking, fuzzy location information, etc., so that the user's real location cannot be easily cracked. It has been shown that if the positioning data provided by the user is not accurate enough, it is still difficult for an attacker to obtain the user's true location. Taking this factor into consideration, our attack method is divided into two stages for the entire attack process: (1) Search stage: cover the area where the targeted user is located with unit discs, and then calculate the minimum dominating set. Use the triangle positioning method to find the minimum precision disc. (2) Inference phase: Considering the existence of errors, an Error-Adjusted Space Partition Attack Algorithm (EASPAA) was proposed during the inference phase. Improved the need for accurate distance information to be able to derive the user's true location. In this study, we focus on the Location Sharing Mechanism with Maximal Coverage Limit to implement the whole attack. Experimental results show that the proposed method still can accurately infer the user's real location even when there is an error in the user's location information.

Analysis on formula of Mongolian medicine for prevention of COVID-19 / 中国中药杂志

The epidemic situation of coronavirus disease 2019(COVID-19) is developing rapidly in the world, and the influence is serious. In this study, the prescription of Mongolian medicine to prevent new type of COVID-19 was investigated. Based on the second edition and the third edition of COVID-19 Mongolian Medicine Prevention and Treatment Guidance Program issued by the Inner Mongolia Autonomous Region Health Commission, using Excel 2007, SPSS Modeler 18, SPSS Statistics 25, Cytoscape 3.7.1 statistical software as a tool, the association rules analysis and cluster analysis of Mongolian medicine included in the standard were carried out. Among the 45 prophylactic prescriptions included in the standard, a total of 34 high-frequency drugs using frequency ≥5 were used, of which Carthami Flos(21 times, 4.46%), Chebulae Fructus(20 times, 4.26%), Moschus(13 times, 2.77%), Myristicae Semen(12 times, 2.55%), Santali Albi Lignum(12 times, 2.55%), and Bovis Calculus(12 times, 2.55%) were the most common. The main drugs for the prevention of COVID-19 were Liang(13 times, 38.23%), Wen(9 times, 26.47%), the flavor was Ku(20 times, 34.48%), Xin(13 times, 22.41%), Gan(11 times, 18.97%), the most used drugs treating hot evil(99 times, 32.46%), treatment of "Heyi" drugs(51 times, 16.72%), treatment of "Badagan" drugs(40 times, 13.11%), treatment of "sticky" drugs(37 times, 12.13%), and a cough, eliminating phlegm and antiasthmatic(31 times, 10.16%), the association rule analysis found that the highest association intensity of the drug pair combination of 11. Clustering analysis using the cluster analysis of inter-group join method found a total of 8 categories. In this study, 45 prescriptions of Mongolian medicine for the prevention of COVID-19 were collec-ted and further analyzed, hoping to provide new ideas for clinical diagnosis and treatment.

Application of imatinib plasma concentration monitoring in the whole process management of gastrointestinal stromal tumor patients / 中华胃肠外科杂志

Objective@#To investigate the significance of monitoring imatinib mesylate (IM) plasma concentrations in patients with gastrointestinal stromal tumor (GIST).@*Methods@#A retrospective descriptive study was carried out. Inclusion criteria: (1) patients with GIST confirmed by postoperative pathology or puncture pathology receiving maintenance therapy of IM; (2) administration of same dose of IM for at least 4 weeks (achieving steady - state plasma concentration). Patients who had severe organ dysfunction, received IM generics, or received IM simultaneously with other drugs significantly affecting IM pharmacokinetic were excluded. A total of 185 patients at the GIST Clinic of Renji Hospital, Shanghai Jiaotong University School of Medicine from August 2018 to May 2019 were enrolled, including 114 males (61.6%) and 71 females (38.4%) with a median age of 60 years old (range, 30-89 years), and 63 advanced cases. Patients receiving preoperative or postoperative adjuvant therapy were given IM 400 mg QD; patients with KIT exon 9 mutation or with disease progression during IM 400 mg QD treatment were given IM 600 mg QD. If the patient had adverse reactions such as myelosuppression during the medication, IM would be reduced or given BID per day. The peripheral venous blood was collected (22 to 24 hours after the last dose for patients who took IM QD and 2 hours before the first dose per day for those who took IM BID). IM plasma concentration was measured through high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Correlation analysis between IM plasma concentration results and clinical data was performed using linear regression analysis.@*Results@#A total of 241 stable blood samples of IM plasma concentration from 185 patients were finally collected. The IM plasma concentrations were significantly different between the doses of 300 mg/d and 400 mg/d [(942.4±433.5) μg/L vs. (1340.0±500.1) μg/L, t=6.317, P<0.001], and between 400 mg/d and 600 mg/d [(1340.0±500.1) μg/L vs. (2188.0±875.5) μg/L, t=3.557, P=0.004]. Among the blood samples of 57 patients receiving IM 300 mg/d, the IM plasma concentration of the advanced patients was significantly lower than that of the non-advanced patients [(795.6±225.8) μg/L vs. (992.2±484.4) μg/L, t=2.088, P=0.042]. Among the 137 blood samples of patients receiving IM 400 mg/d, the IM plasma concentration was higher in patients aged >60 years than those aged ≤60 years [(1461.0±595.3) μg/L vs. (1240.0±380.9) μg/L, t=2.528, P=0.013] and the IM plasma concentration of cases with diarrhea was significantly lower than that of those without diarrhea [(745.8±249.6) μg/L vs. (1382.0±486.9) μg/L, t=6.794, P<0.001]. Gender, primary location, surgical procedure, mutated gene, mutation type, or time of administration was associated with IM plasma concentration no matter in patients taking IM doses of 400 mg/d or 300 mg/d (all P>0.05). Regression analysis showed that body mass (P=0.004 and P=0.019), body mass index (P=0.016 and P=0.042), and body surface area (P=0.007 and P=0.028) were all negatively correlated with IM plasma concentrations in patients taking IM doses of 300 mg/d and 400 mg/d. Within the 137 patients who received a fixed oral dose of 400 mg/d IM, 17 patients received oral 200 mg BID, whose IM plasma drug concentration was not significantly different compared with that of 120 patients who received 400 mg IM QD [(1488.0±408.3) μg/L vs. (1319.0±509.7) μg/L, t=1.307, P=0.193].@*Conclusions@#Monitoring IM plasma concentration is significant throughout the whole process of management of GIST patients receiving IM treatment. In particular, regular monitoring IM plasma concentration and developing appropriate treatment strategies can bring better therapeutic benefits for patients with low doses, diarrhea, advanced condition and older age.

Minutes of the 103rd annual meeting of American College of Surgeons / 中华消化外科杂志

The 103rd annual meeting of American College of Surgeons (ACS) was held in Santiago on 22-26 October 2017.The annual meeting of ACS is not only the largest clinical surgical meeting in the world,but also a platform for global surgeons to learn from each other and enhance communication and friendship.The theme of this conference is to do what's right for the patients.This is not only the discussion in the field of surgical technology,but also the related contents,including medical education,professional ethics and humanities.This conference discussed the new progress of surgical treatment,which will have an aspiring impact on surgical practice and professional technology development,and further benefit the patients.

Protective effect of cornel iridoid glycoside on hepatocytes injured by D-galactosamine/tumor necrosis factor-α / 中国药理学通报

Aim To determine the effect of cornel iri-doid glycoside ( CIG ) on human hepatocyte cell line (L-02) injured by D-galactosamine (GalN) and tumor necrosis factor-α( TNF-α) .Methods Firstly, CIG was extracted , separated and purified . Cell lesion model injured by D-GalN/TNF-αwas tested by MTT method.T-AOC, SOD, MDA and calcium ion concen-tration were taken as indicators to study the effects of CIG on L-02 cell injured by D-GalN/TNF-α.The ex-pression of p-PERK, p-eIF-2α, caspase-3 protein were detected by Western blot .Results 44 mg · L-1 D-GalN and 100 μg · L-1 TNF-αwere suitable for L-02 cell lesion model.CIG high, middle, low concentra-tion group could significantly increase the L-02 cell ac-tivity by 21％, 13％, 8％, respectively and SOD activity and T-AOC ability as well compared with model group.At the same time, they markedly reduced the MDA activity except the low concentration .Three con-centrations of CIG could reduce the expression of endo-plasmic reticulum stress related protein PERK , eIF-2αand apoptosis-associated protein caspase-3. Conclu-sions CIG could protect L-02 cells injured by D-GalN/TNF-α.Increasing the cellular antioxidant abili-ty, reducing the damage of endoplasmic reticulum stress and the expression of apoptosis-associated protein may be the possible mechanism .

Clinicopathological classification and prognostic factors of gastrointestinal neuroendocrine neoplasms: an analysis of 119 cases / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics, pathological classification and prognostic factors of gastrointestinal neuroendocrine neoplasms (GI-NENs).</p><p><b>METHODS</b>Clinicopathological data of 119 GI-NENs patients at Shanghai Renji Hospital from November 2007 to December 2016 were analyzed retrospectively. According to the classification and grading criteria of the WHO Neuroendocrine Tumor 2010 edition, patients were classified pathologically to realize the malignant degree of tumors. The overall survival rate was calculated by Kaplan-Meier curve, the prognostic risk factors were analyzed by Cox regression model, and the factors including the platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) were included in the analysis in addition to the routine clinicopathological factors.</p><p><b>RESULTS</b>Of 119 patients with GI-NENs, there were 83 cases (69.7%) of male and 36 cases (30.3%) of female. The age of patients ranged from 24 to 86 (median 61) years. Tumor locations included the stomach(n=70, 58.8%), duodenum(n=10, 8.4%), small intestine(n=2, 1.7%), appendix(n=3, 2.5%), colon(n=12, 10.1%), and rectum(n=22, 18.5%). The tumor diameter was 0.6 to 20 cm, the mean diameter was 5.4 cm, and the median diameter was 4 cm. There were 25 cases of G1 neuroendocrine tumor (NET), 7 cases of G2 NET and 87 cases of G3 neuroendocrine carcinoma (NEC). Among the 119 patients, 113 cases (95%) had complete follow-up, and the median follow-up was 75 (1 to 112) months. The 5-years overall survival rate was 58.4%. The survival rate of G1 NET, G2 NET and G3 NEC were 100%, 71.4%, 44.4%, and the difference was statistically significant (P=0.000). Univariate analysis showed that age ≥61 years (P=0.000), tumor located in the stomach, duodenum and colon (P=0.041), tumor size ≥4 cm (P=0.002), pathology classification of G3 NEC (P=0.000), late TNM staging (P=0.000) and blood PLR ≥133 (P=0.017) were associated with lower 5-year survival rate, but blood NLR level was not(P=0.263). Multivariate analysis showed that the patient age (HR=3.036, 95%CI: 1.548 to 5.956, P=0.001), the pathology classification(HR = 1.852, 95%CI:1.099 to 3.122, P=0.021), lymph node metastasis (HR=2.635, 95%CI:1.198 to 5.797, P=0.016) and distant metastasis (HR=2.685, 95%CI:1.383 to 5.214, P=0.004) were independent risk factors affecting the prognosis of patients, but the blood PLR level was not (HR=1.735, 95%CI: 0.947 to 3.176, P=0.074).</p><p><b>CONCLUSIONS</b>The malignant degree of GI-NEN is quite high, and the prognosis of patients is relatively poor. The age, pathological type and TNM staging are closely related to the prognosis of patients. Preoperative blood PLR may play a role in the prediction of prognosis, but preoperative blood NLR is not related with the prognosis of patients.</p>

The application of longitudinal stepped case teaching in the geriatrics education / 中华医学教育探索杂志

Case teaching method has been widely used in clinical medicine teaching.Because of the complicated diseases in elderly patients and the individual differences,it is difficult to achieve the goal of teaching only through several cases.Typical cases of different level are selected according to students' different learning stages and difficulty degree in longitudinal stepped case teaching.The students can gradually understand and master the theoretical knowledge through this method.In addition,their clinical thinking and the ability of solving practical problems can also be trained continuously.Preliminary practice shows that this teaching method is more suitable for the development of modern medical education and the needs of teaching.

Protective effects of activated protein C on neurovascular unit in a rat model of intrauterine infection-induced neonatal white matter injury.

Activated protein C (APC), a natural anticoagulant, has been reported to exert direct vasculoprotective, neural protective, anti-inflammatory, and proneurogenic activities in the central nervous system. This study was aimed to explore the neuroprotective effects and potential mechanisms of APC on the neurovascular unit of neonatal rats with intrauterine infection-induced white matter injury. Intraperitoneal injection of 300 µg/kg lipopolysaccharide (LPS) was administered consecutively to pregnant Sprague-Dawley rats at embryonic days 19 and 20 to establish the rat model of intrauterine infection- induced white matter injury. Control rats were injected with an equivalent amount of sterile saline on the same time. APC at the dosage of 0.2 mg/kg was intraperitoneally injected to neonatal rats immediately after birth. Brain tissues were collected at postnatal day 7 and stained with hematoxylin and eosin (H&E). Immunohistochemistry was used to evaluate myelin basic protein (MBP) expression in the periventricular white matter region. Blood-brain barrier (BBB) permeability and brain water content were measured using Evens Blue dye and wet/dry weight method. Double immunofluorescence staining and real-time quantitative PCR were performed to detect microglial activation and the expression of protease activated receptor 1 (PAR1). Typical pathological changes of white matter injury were observed in rat brains exposed to LPS, and MBP expression in the periventricular region was significantly decreased. BBB was disrupted and the brain water content was increased. Microglia were largely activated and the mRNA and protein levels of PAR1 were elevated. APC administration ameliorated the pathological lesions of the white matter and increased MBP expression. BBB permeability and brain water content were reduced. Microglia activation was inhibited and the PAR1 mRNA and protein expression levels were both down-regulated. Our results suggested that APC exerted neuroprotective effects on multiple components of the neurovascular unit in neonatal rats with intrauterine infection- induced white matter injury, and the underlying mechanisms might involve decreased expression of PAR1.

Neuroprotective effects of activated protein C on intrauterine inflammation-induced neonatal white matter injury are associated with the downregulation of fibrinogen-like protein 2/fibroleukin prothrombinase and the inhibition of pro-inflammatory cytokine expression.

Maternal intrauterine inflammation or infection is an important risk factor for neonatal cerebral white matter injury (WMI) and future neurological deficits. Activated protein C (APC), a natural anticoagulant, has been shown to exhibit anti-inflammatory, anti-apoptotic, profibrinolytic and cytoprotective activities. Recent studies have demonstrated that the novel prothrombinase, fibrinogen-like protein 2 (fgl2), contributes to the pathogenesis of a number of inflammatory diseases through the generation of fibrin. Thus, we hypothesized that APC may regulate coagulant and inflammatory processes and improve brain injury in an experimental rat model of intrauterine inflammation-induced WMI. The animal model was established by the administration of an intraperitoneal injection of lipopolysaccharide (LPS) to pregnant Sprague-Dawley rats on embryonic day (E)17 and E18. APC was administered intraperitoneally 30 min after the second LPS injection. The expression of fgl2 and the pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß expression in the placentas and fetal brains was determined on E19. Nerve cell death, the brain water content and protease-activated receptor 1 (PAR1) and nuclear factor κB (NF-κB) p65 expression was detected in the fetal brains. WMI in the neonatal rat brains was evaluated by hematoxylin and eosin (H&E) staining and immunohistochemistry for myelin basic protein (MBP). The results revealed that APC markedly reduced the LPS-induced increase in fgl2 expression and fibrin deposition, as well as the production of the pro-inflammatory cytokines, TNF-α, IL-6 and IL-1ß, in the placentas and fetal brains. In addition, APC attenuated cerebral apoptosis and brain edema, downregulated PAR1 and NF-κB p65 expression in the fetal brains, and improved hypomyelination and structural disturbances in the periventricular area of the neonatal rat brains. Our observations provide evidence that APC attenuates fetal neuroinflammation and the associated secondary WMI in the developing brain by inhibiting the expression of fgl2 and pro-inflammatory mediators, suggesting that APC may be a potential therapeutic approach for intrauterine inflammation-induced neonatal brain injury.

Effect and mechanisms of aspirin on rat cardial fibroblast proliferation induced by aldosterone / 军事医学

Objective To investigate the effects of aspirin(aspi) on rat cardiac fibroblasts (CFs) proliferation induced by aldosterone(ald) and the underlying molecular mechanisms .Methods Primary CFs from 1-3 day neonatal rats were digested by 0.08%trypsin and then purified by differential adhesion .The rats were divided into four groups:control group, DMEM medium ( free calf serum ) , ald group [ DMEM medium ( free calf serum ) +ald 1 ×10 -8 mol/L ] , aspi group [DMEM medium (free calf serum)+ald 1 ×10 -8 mol/L+aspi 1.11 ×10 -6 mol/L] and spiro group [DMEM medium (free calf serum)+ald 1 ×10 -8 mol/L +spiro 1 ×10 -6 mol/L].The morphology of CFs was assayed by HE staining methods .MTT Methods were used to measure cell proliferation .Western blotting was used to determine protein expression of TGF-β-Smad 2,3,4.Results HE Staining results showed that compared with the control group , ald activated cell proliferation and increased the cell division phase significantly (P<0.01).Compared with ald group, aspi+ald as well as spiro+ald could reduce cell division significantly ( P<0 .05 ) .MTT assay showed that compared with control group , ald could significantly improve the metabolism of MTT in CF (P <0.01).Compared with ald group, aspi +ald as well as spiro+ald could reduce the metabolism of MTT (P<0.01).Western blotting revealed that the expression levels of TGF-β-Smad 2, 3, 4 in CF were significantly increased by the stimulation of ald but were significantly reduced in aspi +ald and spiro+ald groups compared with ald group (P<0.01).Conclusion Aspi can inhibit the proliferation of CFs induced by ald,possibly by down-regulating the expression of Smad 2, Smad3 and Smad4.

Enhancing the quality of protein conformation ensembles with relative populations.

The function and dynamics of many proteins are best understood not from a single structure but from an ensemble. A high quality ensemble is necessary for accurately delineating protein dynamics. However, conformations in an ensemble are generally given equal weights. Few attempts were made to assign relative populations to the conformations, mainly due to the lack of right experimental data. Here we propose a method for assigning relative populations to ensembles using experimental residue dipolar couplings (RDC) as constraints, and show that relative populations can significantly enhance an ensemble's ability in representing the native states and dynamics. The method works by identifying conformation states within an ensemble and assigning appropriate relative populations to them. Each of these conformation states is represented by a sub-ensemble consisting of a subset of the conformations. Application to the ubiquitin X-ray ensemble clearly identifies two key conformation states, with relative populations in excellent agreement with previous work. We then apply the method to a reprotonated ERNST ensemble that is enhanced with a switched conformation, and show that as a result of population reweighting, not only the reproduction of RDCs is significantly improved, but common conformational features (particularly the dihedral angle distributions of ϕ 53 and ψ 52) also emerge for both the X-ray ensemble and the reprotonated ERNST ensemble.

Generalized spring tensor models for protein fluctuation dynamics and conformation changes.

BACKGROUND: In the last decade, various coarse-grained elastic network models have been developed to study the large-scale motions of proteins and protein complexes where computer simulations using detailed all-atom models are not feasible. Among these models, the Gaussian Network Model (GNM) and Anisotropic Network Model (ANM) have been widely used. Both models have strengths and limitations. GNM can predict the relative magnitudes of protein fluctuations well, but due to its isotropy assumption, it cannot be applied to predict the directions of the fluctuations. In contrast, ANM adds the ability to do the latter, but loses a significant amount of precision in the prediction of the magnitudes. RESULTS: In this book chapter, we present a single model, called generalized spring tensor model (STeM), that is able to predict well both the magnitudes and the directions of the fluctuations. Specifically, STeM performs equally well in B-factor predictions as GNM and has the ability to predict the directions of fluctuations as ANM. This is achieved by employing a physically more realistic potential, the Go-like potential. The potential, which is more sophisticated than that of either GNM or ANM, though adds complexity to the derivation process of the Hessian matrix (which fortunately has been done once for all and the MATLAB code is freely available electronically at http://www.cs.iastate.edu/~gsong/STeM ), causes virtually no performance slowdown. In addition, we show that STeM can be further extended to an all-atom model and protein fluctuation dynamics computed by all-atom STeM matches closely with that by Normal Mode Analysis (NMA). CONCLUSIONS: Derived from a physically more realistic potential, STeM proves to be a natural solution in which advantages that used to exist in two separate models, namely GNM and ANM, are achieved in one single model. It thus lightens the burden to work with two separate models and to relate the modes of GNM with those of ANM at times. By examining the contributions of different interaction terms in the Go potential to the fluctuation dynamics, STeM reveals, (i) a physical explanation for why the distance-dependent, inverse distance square (i.e., 1/r (2)) spring constants perform better than the uniform ones, and (ii), the importance of three-body and four-body interactions to properly modeling protein dynamics.STeM is not limited to coarse-grained protein models that use a single bead, usually the alpha carbon, to represent each residue. The core idea of STeM, deriving the Hessian matrix directly from a physically realistic potential, can be extended to all-atom models as well. We did this and discovered that all-atom STeM model represents a highly close approximation of NMA, yet without the need for energy minimization.

Retrospective clinical analysis of heterotopic pancreas misdiagnosed as gastrointestinal stromal tumors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To improve the differential diagnosis and treatment between heterotopic pancreas and gastrointestinal stromal tumor.</p><p><b>METHOD</b>Clinical and follow-up data of 14 cases who were diagnosed preoperatively as gastrointestinal stromal tumor whereas were confirmed as heterotopic pancreas in the gastrointestinal tract by postoperative pathological results in Renji Hospital from January 2007 to June 2013 were analyzed retrospectively.</p><p><b>RESULT</b>There were 9 males and 5 females, aged ranged from 26 to 69 years old. Eight patients had upper abdominal pain, 2 presented with intestinal obstruction, and 4 were incidentally found on routine health check-up. The lesions located at the stomach in 11 cases, at the duodenum in 1 case, and at the jejunum in 2 cases. All the patients underwent operation. Postoperative pathology confirmed the diagnosis of heterotopic pancreas. Among these lesions, 10 cases presented with co-existence of pancreatic acinus and duct as main component with smooth muscle and few gastric mucosa tissues, 3 cases was mainly the pancreatic acinus and 1 case mainly the pancreatic duct and smooth muscle.</p><p><b>CONCLUSIONS</b>Heterotopic pancreas may be misrocognized at gastrointestinal stromal tumors due to non-specific clinical manifestations and effective examination methods. Surgical procedure is the only one and the most effective treatment. Postoperative pathology examination is the most difinitive for differential diagnosis.</p>

Three-in-one agonists for PPAR-α, PPAR-γ, and PPAR-δ from traditional Chinese medicine.

Nowadays, the occurrence of metabolic syndrome, which is characterized by obesity and clinical disorders, has been increasing rapidly over the world. It induces several serious chronic diseases such as cardiovascular disease, dyslipidemia, gall bladder disease, hypertension, osteoarthritis, sleep apnea, stroke, and type 2 diabetes mellitus. Peroxisome proliferator-activated receptors (PPARs), which have three isoforms: PPAR-α, PPAR-γ, and PPAR-δ, are key regulators of adipogenesis, lipid and carbohydrate metabolism, and are potential drug targets for treating metabolic syndrome. The traditional Chinese medicine (TCM) compounds from TCM Database@Taiwan ( http://tcm.cmu.edu.tw/ ) were employed to virtually screen for potential PPAR agonists, and structure-based pharmacophore models were generated to identify the key interactions for each PPAR protein. In addition, molecular dynamics (MD) simulation was performed to evaluate the stability of the PPAR-ligand complexes in a dynamic state. (S)-Tryptophan-betaxanthin and berberrubine, which have higher Dock Score than controls, form stable interactions during MD, and are further supported by the structure-based pharmacophore models in each PPAR protein. Key features include stable H-bonds with Thr279 and Ala333 of PPAR-α, with Thr252, Thr253 and Lys331 of PPAR-δ, and with Arg316 and Glu371 of PPAR-γ. Hence, we propose the top two TCM candidates as potential lead compounds in developing agonists targeting PPARs protein for treating metabolic syndrome.

Efficient mapping of ligand migration channel networks in dynamic proteins.

For many proteins such as myoglobin, the binding site lies in the interior, and there is no obvious route from the exterior to the binding site in the average structure. Although computer simulations for a limited number of proteins have found some transiently open channels, it is not clear if there exist more channels elsewhere or how the channels are regulated. A systematic approach that can map out the whole ligand migration channel network is lacking. Ligand migration in a dynamic protein resembles closely a well-studied problem in robotics, namely, the navigation of a mobile robot in a dynamic environment. In this work, we present a novel robotic motion planning inspired approach that can map the ligand migration channel network in a dynamic protein. The method combines an efficient spatial mapping of protein inner space with a temporal exploration of protein structural heterogeneity, which is represented by a structure ensemble. The spatial mapping of each conformation in the ensemble produces a partial map of protein inner cavities and their inter-connectivity. These maps are then merged to form a super map that contains all the channels that open dynamically. Results on the pathways in myoglobin for gaseous ligands demonstrate the efficiency of our approach in mapping the ligand migration channel networks. The results, obtained in a significantly less amount of time than trajectory-based approaches, are in agreement with previous simulation results. Additionally, the method clearly illustrates how and what conformational changes open or close a channel.