Generation ofthe Stmn2-Cre^(ERT2)mouse line targeting arterial endothelial cells

Endothelial cells(ECs)form a single cell layer that lines the inner surface of all blood and lymphatic vessels,acting as the barrier between vessels and underlying tissues.ECs are not only responsible for the flow of substances and fluid into and out of tissues but are also involved in many processes,such as coagulation,fibrinolysis,and regulation of vascular tone and inflammation.

TCM-HIN2Vec:A strategy for uncovering biological basis of heart qi deficiency pattern based on network embedding and transcriptomic experiment

Objective To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods We predicted and characterized HQD pattern genes using the new strategy,TCM-HIN2Vec,which involves heterogeneous network embedding and transcriptomic experiments.First,a heterogeneous network of traditional Chinese medicine(TCM)patterns was constructed using public databases.Next,we predicted HQD pattern genes using a heterogeneous network-embedding algorithm.We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq.Finally,we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis.Results Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism,signal transduction pathways,and immune processes.Moreover,we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern.Furthermore,herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD.Conclusion Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes,but also deciphering the basis of HQD pattern.Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns,leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.

Clinical proteomics identifies potential biomarkers in Helicobacter pylori for gastrointestinal diseases

The development of gastrointestinal diseases has been found to be associated with Helicobacter pylori (H. pylori) infection and various biochemical stresses in stomach and intestine. These stresses, such as oxidative, osmotic and acid stresses, may bring about bi-directional effects on both hosts and H. pylori, leading to changes of protein expression in their proteomes. Therefore, proteins differentially expressed in H. pylori under various stresses not only reflect gastrointestinal environment but also provide useful biomarkers for disease diagnosis and prognosis. In this regard, proteomic technology is an ideal tool to identify potential biomarkers as it can systematically monitor proteins and protein variation on a large scale of cell’s translational landscape, permitting in-depth analyses of host and pathogen interactions. By performing two-dimensional polyacrylamide gel electrophoresis (2-DE) followed by liquid chromatography-nanoESI-mass spectrometry (nanoLC-MS/MS), we have successfully pinpointed alkylhydroperoxide reductase (AhpC), neutrophil-activating protein and non-heme iron-binding ferritin as three prospective biomarkers showing up-regulation in H. pylori under oxidative, osmotic and acid stresses, respectively. Further biochemical characterization reveals that various environmental stresses can induce protein structure change and functional conversion in the identified biomarkers. Especially salient is the antioxidant enzyme AhpC, an abundant antioxidant protein present in H. pylori. It switches from a peroxide reductase of low-molecular-weight (LMW) oligomers to a molecular chaperone of high-molecular-weight (HMW) complexes under oxidative stress. Different seropositivy responses against LMW or HMW AhpC in H. pylori-infected patients faithfully match the disease progression from disease-free healthy persons to patients with gastric ulcer and cancer. These results has established AhpC of H. pylori as a promising diagnostic marker for gastrointestinal maladies, and highlight the utility of clinical proteomics for identifying disease biomarkers that can be uniquely applied to disease-oriented translational medicine.

Recent advances in CRISPR-based genome editing technology and its applications in cardiovascular research

The rapid development of genome editing technology has brought major breakthroughs in the fields of life science and medicine. In recent years, the clustered regularly interspaced short palindromic repeats(CRISPR)-based genome editing toolbox has been greatly expanded, not only with emerging CRISPR-associated protein(Cas) nucleases, but also novel applications through combination with diverse effectors. Recently, transposon-associated programmable RNA-guided genome editing systems have been uncovered, adding myriads of potential new tools to the genome editing toolbox. CRISPR-based genome editing technology has also revolutionized cardiovascular research. Here we first summarize the advances involving newly identified Cas orthologs, engineered variants and novel genome editing systems, and then discuss the applications of the CRISPR-Cas systems in precise genome editing, such as base editing and prime editing. We also highlight recent progress in cardiovascular research using CRISPR-based genome editing technologies, including the generation of genetically modified in vitro and animal models of cardiovascular diseases(CVD) as well as the applications in treating different types of CVD. Finally, the current limitations and future prospects of genome editing technologies are discussed.

Uncovering the miRNA-mediated regulatory network involved in Ma bamboo(Dendrocalamus latiflorus)de novo shoot organogenesis

Bamboo is an important non-timber forest product and is well-known for its reluctance to regenerate.Recently we have established a de novo shoot organogenesis(DNSO)protocol in Ma bamboo(Dendrocalamus latiflorus)and revealed the transcriptomic dynamics during Ma bamboo regeneration,which suggested the potential roles of Ma bamboo microRNAs(DlamiRNAs)in this process.However,how DlamiRNAs regulate bamboo DNSO is poorly understood.Here we performed integrated analysis with sRNAome,degradome,and transcriptome sequencing by using samples covering the four stages of the bamboo DNSO process.A total of 727 DlamiRNAs showed differential expression during the bamboo DNSO process,and the core DlamiRNA-DlamRNA-mediated regulatory networks for bamboo DNSO were constructed.Based on the results,DlamiR156 was selected for further functional characterization of its potential roles in bamboo DNSO.Transgenic bamboos with increased DlamiR156 levels exhibited an enhancement in their regeneration efficiency.Conversely,when DlamiR156 levels were downregulated,the regeneration efficiencies of transgenic bamboos decreased.Our findings show that the DlamiRNA-mediated regulatory pathways are significant in the process of bamboo regeneration and will contribute to our understanding of the molecular mechanisms governing plant organogenesis in a more comprehensive manner.

Transcriptome Analysis of Auxin Drives Cone Size Regulation in Fokienia hodginsii

As the reproductive organ of the endangered species Fokienia hodginsii,the size of the cones is a constraint on the reproductive renewal of the population.In this study,the molecular basis of the influence of cone size on F.hodginsii was elucidated by comparing the phenotype,biochemistry,and transcriptome of two cultivars of F.hodginsii(‘FJ431’and‘FJ415’).The two cultivars differed significantly in cone size,with FJ431 having a significantly larger cone size and weight than FJ415,1.32 and 1.90 times that of FJ415,respectively.RNA-Seq analysis of both cultivars retrieved 75,940 genes whose approximate functions were classified as the pathway of response to endogenous stimulus and response to hormone and showed significant differences in the auxin-activated signaling pathway,particularly the MAPK signaling pathway-plant.Furthermore,the endogenous IAA content was significantly higher in FJ431 than in FJ415,and 1.58 and 1.29 times more IAA was present in immature and mature cones,respectively.Moreover,exogenous IAA treatment significantly induced the expression of the MAPK pathway-related gene TRINITY_DN10564_c0_g1 and significantly inhibited the expression of the MAPK pathwayrelated gene TRINITY_DN17056_c0_g1.Our work suggests that IAA can affect the cone size of F.hodginsii,most probably through the MAPK pathway.This has high theoretical and practical significance for the improvement of genetic breeding and the further cultivation of quality germplasm resources of F.hodginsii.

MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth

A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi （n = 10） and primary malignant melanomas （n = 10）, using quantitative real-time PCR. Differential expression was found for 72 microRNAs. Members of the let-7 family of microRNAs were significantly downregulated in primary melanomas as compared with benign nevi, suggestive for a possible role of these molecules as tumor suppressors in malignant melanoma. Interestingly, similar findings had been described for lung and colon cancer. Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1, D3, and A, and cyclin-dependent kinase （Cdk） 4, all of which had been described to play a role in melanoma development. The effect oflet-7b on protein expression was due to targeting of 3＇-untranslated regions （3＇UTRs） of individual mRNAs, as exemplified by reporter gene analyses for cyclin D1. In line with its downmodulating effects on cell cycle regulators, let-7b inhibited cell cycle progression and anchorage-independent growth of melanoma cells. Taken together, these findings not only point to new regulatory mechanisms of early melanoma development, but also may open avenues for future targeted therapies of this tumor.

Identification of CD13,CD107a,and CD164 as novel basophil-activation markers and dissection of two response patterns in time kinetics of IgE-de-pendent upregulation

Using two-colour flow cytometry>200 antibodies submitted to the 8^(th) International Workshop of Human Leukocyte Differentiation Antigens(HLDA8)have been analyzed for their reactivity with resting and activated CD203c^(+)basophils.Four antibodies either non-reactive or weakly reactive with resting basophils exhibited an increased reactivity with basophils activated by anti-IgE-mediated cross-linking of the high affinity IgE receptor(FcεRI).These include antibod-ies against CD164(WS-80160,clone N6B6 and WS-80162,clone 67D2),as well as two reagents with previously unknown specificities that were identified as CD13(WS-80274,clone A8)and CD107a(WS-80280,clone E63-880).The activation patterns followed either the“CD203c-like”or“CD63-like”activation profile.The CD203c profile is characterized by a rapid and significant upregulation(of CD13,CD164,and CD203c),reaching maximum levels after 5-15 min of stimulation.The phosphoinositide-3-kinase(PI3K)-specific inhibitor wortmannin inhibited the upregulation of these markers whereas 12-O-tetradecanoyl-phorbol-13-acetate(TPA)induced a rapid and FcεRI-independent upregulation within 1-2 min.In the CD63 profile,maximum upregulation(of CD63 and CD107a)was detected only after 20-40 min,and upregulation by TPA reached maximum levels after 60 min.In summary,our data identify CD13,CD107a,and CD164 as novel basophil-activation antigens.Based on time kinetics of upregulation,we hypothesize that molecules of the“CD203c group”and the“CD63 group”are linked to two different mechanisms of basophil activation.

Aberrant activation of nuclear factor of activated T cell 2 in lamina propria mononuclear cells in ulcerative colitis

AIM:To investigate the role of nuclear factor of activated T cell 2(NFAT2),the major NFAT protein in peripheral T cells,in sustained T cell activation and intractable inflammation in human ulcerative colitis(UC). METHODS:We used two-dimensional gel-electrophoresis, immunohistochemistry,double immunohistochemical staining,and confocal microscopy to inspect the expression of NFAT2 in 107,15,48 and 5 cases of UC, Crohn's disease(CD),non-specific colitis,and 5 healthy individuals,respectively. RESULTS:Up-regulation with profound nucleo- translocation/activation of NFAT2 of lamina propria mononuclear cells(LPMC)of colonic mucosa was found specifically in the affected colonic mucosa from patients with UC,as compared to CD or NC(P<0.001,Kruskal- Wallis test).Nucleo-translocation/activation of NFAT2 primarily occurred in CD8+T,but was less prominent in CD4+T cells or CD20+B cells.It was strongly associated with the disease activity,including endoscopic stage (τ=0.2145,P=0.0281)and histologic grade(τ=0.4167, P<0.001). CONCLUSION:We disclose for the first time the nucleo-translocation/activatin of NFAT2 in lamina propria mononuclear cells in ulcerative colitis.Activation of NFAT2 was specific for ulcerative colitis and highly associated with disease activity.Since activation of NFAT2is implicated in an auto-regulatory positive feedback loop of sustained T-cell activation and NFAT proteins play key roles in the calcium/calcineurin signaling pathways,our results not only provide new insights into the mechanism for sustained intractable inflammation,but also suggest the calcium-calcineurin/NFAT pathway as a new therapeutic target for ulcerative colitis.

Sustained Akt signaling in articular chondrocytes causes osteoarthritis via oxidative stress-induced senescence in mice

Osteoarthritis(OA) is an age-related disorder that is strongly associated with chondrocyte senescence. The causal link between disruptive PTEN/Akt signaling and chondrocyte senescence and the underlying mechanism are unclear. In this study, we found activated Akt signaling in human OA cartilage as well as in a mouse OA model with surgical destabilization of the medial meniscus.Genetic mouse models mimicking sustained Akt signaling in articular chondrocytes via PTEN deficiency driven by either Col2a1-Cre or Col2a1-Cre^(ERT2) developed OA, whereas restriction of Akt signaling reversed the OA phenotypes in PTEN-deficient mice.Mechanistically, prolonged activation of Akt signaling caused an accumulation of reactive oxygen species and triggered chondrocyte senescence as well as a senescence-associated secretory phenotype, whereas chronic administration of the antioxidant N-acetylcysteine suppressed chondrocyte senescence and mitigated OA progression in PTEN-deficient mice. Therefore,inhibition of Akt signaling by PTEN is required for the maintenance of articular cartilage. Disrupted Akt signaling in articular chondrocytes triggers oxidative stress-induced chondrocyte senescence and causes OA.

Fractionation of gamma-glutamyltransferase in patients with nonalcoholic fatty liver disease and alcoholic liver disease

AIM To assess how serum gamma-glutamyltransferase(GGT) fractions vary in patients with alcoholic liver disease(ALD) and non-alcoholic fatty liver disease(NAFLD). METHODS Serum samples were obtained from 14 patients with biopsy-proven alcoholic liver diseases and 9 patients with biopsy proven non-alcoholic fatty liver disease. In addition to these biopsy-proven cases, 16 obese(body mass index > 25) patients without any history of alcohol consumption but with a fatty liver on ultrasound examination and with elevated GGT were included for an additional analysis. Serum GGT fractionation was conducted by high-performance gel filtration liquid chromatography and was separated into the four fractions, big-GGT, medium-GGT, small-GGT(s-GGT), and free-GGT(f-GGT).RESULTS The results were expressed as a ratio of each fraction including the total GGT(t-GGT). The s-GGT/t-GGT ratioswere lowest for the control group and highest for the ALD group. The differences between the control and NAFLD groups and also between the NAFLD and ALD groups were statistically significant. In contrast, the f-GGT/t-GGT ratios were highest in the control group and lowest in the ALD group, with the differences being statistically significant. As a result, the s-GGT/f-GGT ratios were markedly increased in the NAFLD group as compared with the control group. The increase of the s-GGT/t-GGT ratios, the decrease of the f-GGT/t-GGT ratios, and the increase of s-GGT/F-GGT ratios as compared with the control group subjects were also found in obese patients with clinically diagnosed fatty change of the liver.CONCLUSION Serum GGT fractionation by high-performance gel filtration liquid chromatography is potentially useful for the differential diagnosis of ALD and NAFLD.

Drug repurposing for cancer treatment through global propagation with a greedy algorithm in a multilayer network

Objective:Drug repurposing,the application of existing therapeutics to new indications,holds promise in achieving rapid clinical effects at a much lower cost than that of de novo drug development.The aim of our study was to perform a more comprehensive drug repurposing prediction of diseases,particularly cancers.Methods:Here,by targeting 4,096 human diseases,including 384 cancers,we propose a greedy computational model based on a heterogeneous multilayer network for the repurposing of 1,419 existing drugs in Drug Bank.We performed additional experimental validation for the dominant repurposed drugs in cancer.Results:The overall performance of the model was well supported by cross-validation and literature mining.Focusing on the top-ranked repurposed drugs in cancers,we verified the anticancer effects of 5 repurposed drugs widely used clinically in drug sensitivity experiments.Because of the distinctive antitumor effects of nifedipine(an antihypertensive agent)and nortriptyline(an antidepressant drug)in prostate cancer,we further explored their underlying mechanisms by using quantitative proteomics.Our analysis revealed that both nifedipine and nortriptyline affected the cancer-related pathways of DNA replication,the cell cycle,and RNA transport.Moreover,in vivo experiments demonstrated that nifedipine and nortriptyline significantly inhibited the growth of prostate tumors in a xenograft model.Conclusions:Our predicted results,which have been released in a public database named The Predictive Database for Drug Repurposing(PAD),provide an informative resource for discovering and ranking drugs that may potentially be repurposed for cancer treatment and determining new therapeutic effects of existing drugs.

Efficacy of nanofibrous conduits in repair of longsegment sciatic nerve defects

Our previous studies have histomorphologically confirmed that nanofibrous poly（3-hydroxybutyrate- co-3-hydroxyvalerate） conduit can be used to repair 30-mm-long sciatic nerve defects. However, the repair effects on rat behaviors remain poorly understood. In this study, we used nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit and autologous sciatic nerve to bridge 30-ram-long rat sciatic nerve gaps. Within 4 months after surgery, rat sciatic nerve functional re- covery was evaluated per month by behavioral analyses, including toe out angle, toe spread anal- ysis, walking track analysis, extensor postural thrust, swimming test, open-field analysis and no- ciceptive function. Results showed that rat sciatic nerve functional recovery was similar after nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit and autologous nerve grafting. These findings suggest that nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit is suitable in use for repair of long-segment sciatic nerve defects.

The prognostic value of serum C-reactive protein-bound serum amyloid A in early-stage lung cancer

Background:Elevated levels of serum C-reactive protein(CRP) have been reported to have prognostic significance in lung cancer patients.This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value.Methods:CRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis.CRP-bound serum amyloid A(CRP-SAA) was evaluated by coimmunoprecipitation(IP).Serum samples from two independent cohorts with lung cancer(retrospective cohort,242patients;prospective cohort,222 patients) and healthy controls(159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay.Results:CRP-SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis.CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media.The level of CRP-SAA was significantly higher in patients than in healthy controls(0.37 ± 0.58 vs.0.03 ± 0.04,P < 0.001).Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer.The elevation of CRPSAA was associated with lower survival rates for both the retrospective(hazard ration[HR]= 2.181,95%confidence interval[CI]= 1.641-2.897,P < 0.001) and the prospective cohorts(HR = 2.744,95%CI = 1.810-4.161,P < 0.001).Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer.Remarkably,in stages l-ll patients,only CRP-SAA,not total SAA or CRP,showed significant association with overall survival in two cohorts.Moreover,univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients.Conclusion:CRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP,especially in earlystage patients.

Global characterization of modifications to the charge isomers of IgG antibody

Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is challenging.We intended to quantitatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge heterogeneity.The CIs of antibodies were fractionated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three levels.First,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation status.Second,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were identified.Peptide mapping showed nonuniform deamidation and glycoform distribution among CIs.In total,10 N-glycoforms were detected by peptide mapping.Finally,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched glycopeptides.Qualitative and quantitative analyses demonstrated the dynamics of 24 N-glycoforms.The results revealed that sialic acid modification is a critical factor accounting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight analyses.This study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.

Toll-like receptor 5-mediated signaling enhances liver regeneration in mice

Background:Toll-like receptor 5(TLR5)-mediated pathways play critical roles in regulating the hepatic immune response and show hepatoprotective effects in mouse models of hepatic diseases.However,the role of TLR5 in experimental models of liver regeneration has not been reported.This study aimed to investigate the role of TLR5 in partial hepatectomy(PHx)-induced liver regeneration.Methods:We performed 2/3 PHx in wild-type(WT)mice,TLR5 knockout mice,or TLR5 agonist CBLB502 treated mice,as a model of liver regeneration.Bacterial flagellin content was measured with ELISA,and hepatic TLR5 expression was determined with quantitative PCR analyses and flow cytometry.To study the effects of TLR5 on hepatocyte proliferation,we analyzed bromodeoxyuridine(BrdU)incorporation and proliferating cell nuclear antigen(PCNA)expression with immunohistochemistry(IHC)staining.The effects of TLR5 during the priming phase of liver regeneration were examined with quantitative PCR analyses of immediate early gene mRNA levels,and with Western blotting analysis of hepatic NF-κB and STAT3 activation.Cytokine and growth factor production after PHx were detected with real-time PCR and cytometric bead array(CBA)assays.Oil Red O staining and hepatic lipid concentrations were analyzed to examine the effect of TLR5 on hepatic lipid accumulation after PHx.Results:The bacterial flagellin content in the serum and liver increased,and the hepatic TLR5 expression was significantly up-regulated in WT mice after PHx.TLR5-deficient mice exhibited diminished numbers of BrdU-and PCNA-positive cells,suppressed immediate early gene expression,and decreased cytokine and growth factor production.Moreover,PHx-induced hepatic NF-κB and STAT3 activation was inhibited in Tlr5–/–mice,as compared with WT mice.Consistently,the administration of CBLB502 significantly promoted PHx-mediated hepatocyte proliferation,which was correlated with enhanced production of proinflammatory cytokines and the recruitment of macrophages and neutrophils in the liver.Furthermore,Tlr5–/–mice displayed significantly lower hepatic lipid concentrations and smaller Oil Red O positive areas than those in control mice after PHx.Conclusions:We reveal that TLR5 activation contributes to the initial events of liver regeneration after PHx.Our findings demonstrate that TLR5 signaling positively regulates liver regeneration and suggest the potential of TLR5 agonist to promote liver regeneration.

Development and Validation of a Simoa Assay for Determination of Recombinant Batroxobin in Human Serum

Recombinant batroxobin(S3101)is a thrombin-like serine protease that binds to fibrinogen or is taken up by the reticuloendothelial system.A literature survey showed no adequate method that could determine sufficient concentrations to evaluate pharmacokinetic parameters for phase I clinical studies.Therefore,a sensitive method is urgently needed to support the clinical pharmacokinetic evaluation of S3101.In this study,a sensitive bioanalytical method was developed and validated,using a Quanterix single molecular array(Simoa)assay.Moreover,to thoroughly assess the platform,enzyme-linked immunosorbent assay and electrochemiluminescence assay were also developed,and their performance was compared with that of this novel technology platform.The assay was validated in compliance with the current guidelines.Measurements with the Simoa assay were precise and accurate,presenting a valid assay range from 6.55 to 4000 pg/mL.The intra-and inter-run accuracy and precision were within-19.3%to 15.3%and 5.5%to 17.0%,respectively.S3101 was stable in human serum for 280 days at-20℃and-70℃,for 2 h prior to pre-treatment and 24 h post pre-treatment at room temperature(22℃-28℃),respectively,and after five and two freeze-thaw cycles at-70℃and-20oC,respectively.The Simoa assay also demonstrated sufficient dilution linearity,assay sensitivity,and parallelism for quantifying S3101 in human serum.The Simoa assay is a sensitive and adequate method for evaluating the pharmacokinetic parameters of S3101 in human serum.

Prediction of risk of cardiovascular events in patients with mild to moderate coronary artery lesions using naive Bayesian networks

Background This prospective study integrated multiple clinical indexes and inflammatory markers associated with coronary atherosclerotic vulnerable plaque to establish a risk prediction model that can evaluate a patient with certain risk factors for the likelihood of the occurrence of a coronary heart disease event within one year. Methods This study enrolled in 2686 patients with mild to moderate coronary artery lesions. Eighty-five indexes were recorded, included baseline clinical data, laboratory studies, and procedural characteristics. During the 1-year follow-up, 233 events occurred, five patients died, four patients suffered a nonfatal myocardial infarction, four patients underwent revascularization, and 220 patients were readmitted for angina pectoris. The Risk Estimation Model and the Simplified Model were conducted using Bayesian networks and compared with the Single Factor Models. Results The area under the curve was 0.88 for the Bayesian Model and 0.85 for the Simplified Model, while the Single Factor Model had a maximum area under the curve of 0.65. Conclusion The new models can be used to assess the short-term risk of individual coronary heart disease events and may assist in guiding preventive care.

Effect of axial length and anterior chamber depth on the peripheral refraction profile

AIM:To evaluate the effect of axial length(AL)and anterior chamber depth(ACD)on peripheral refractive profile in myopic patients compared to emmetropic participants.METHODS:This cross-sectional study was conducted in right eyes of 58 participants of whom 38 were emmetropic and 20 were myopic.Central and peripheral refraction were measured at 10°,20°,and 30°eccentricities in nasal and temporal fields using an open-field autorefractor.The Lenstar LS900 was used to measure ACD and AL.The participants were divided into three groups of short(<22.5 mm),normal(22.5-24.5 mm),and long eye(>24.5 mm)according to AL and three groups of low ACD(<3.00 mm),normal ACD(3.00-3.60 mm),and high ACD(>3.60 mm)according to ACD.RESULTS:The mean age of the participants was 22.26±3.09 y(range 18-30 y).The peripheral mean spherical refractive error showed a hypermetropic shift in myopic and emmetropic groups although this shift was more pronounced in the myopic group.The results showed significant changes in the spherical equivalent,J0,and J45 astigmatism in all gazes with an increase in eccentricity(P<0.001).The pattern of refractive error changes was more noticeable in long and short eyes versus normal AL eyes.Moreover,the pattern of peripheral refractive changes was much more prominent in the high ACD group versus the normal ACD group and in the normal ACD group versus the low ACD group.CONCLUSION:Peripheral refraction changes are greater in participants with AL values outside the normal range and deeper ACD values compared to participants with normal AL and ACD.

Nanofibrous nerve conduits for repair of 30-mm-long sciatic nerve defects

It has been confirmed that nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） nerve conduit can promote peripheral nerve regeneration in rats. However, its efficiency in repair of over 30-mm-long sciatic nerve defects needs to be assessed. In this study, we used a nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） nerve conduit to bridge a 30-mm-long gap in the rat sciatic nerve. At 4 months after nerve conduit implantation, regenerated nerves were macroscopi- cally observed and histologically assessed. In the nanofibrous graft, the rat sciatic nerve trunk had been reconstructed by restoration of nerve continuity and formation of myelinated nerve fiber. There were Schwann cells and glial cells in the regenerated nerves. Masson＇s trichrome staining showed that there were no pathological changes in the size and structure of gastrocnemius muscle cells on the operated side of rats. These findings suggest that nanofibrous poly（3-hydroxybutyrate-co-3- hydroxyvalerate） nerve conduit is suitable for repair of long-segment sciatic nerve defects.