Semaphorin 7A impairs barrier function in cultured human corneal epithelial cells in a manner dependent on nuclear factor-kappa B

●AIM:To evaluate the role of semaphorin 7A(Sema7A)and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells(HCEs).●METHODS:Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0,125,250,or 500 ng/mL for 24,48,or 72h in vitro.Transepithelial electrical resistance(TEER)as well as Dextran-fluorescein isothiocyanate(FITC)permeability assays were conducted to assess barrier function.To quantify tight junctions(TJs)such as occludin and zonula occludens-1(ZO-1)at the mRNA level,reverse transcriptionpolymerase chain reaction(RT-PCR)analysis was performed.Immunoblotting was used to examine the activity of the nuclear factor-kappa B(NF-κB)signaling pathway and the production of TJs proteins.Immunofluorescence analyses were employed to localize the TJs.Enzyme-linked immunosorbent assay(ELISA)and RT-PCR were utilized to observe changes in interleukin(IL)-1βlevels.To investigate the role of NF-κB signaling activation and IL^(-1)βin Sema7A’s anti-barrier mechanism,we employed 0.1μmol/L IκB kinase 2(IKK2)inhibitor IV or 500 ng/mL IL^(-1)receptor(IL-1R)antagonist.●RESULTS:Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time-and dose-dependent manner,as well as altering the localization of TJs.Furthermore,Sema7A stimulated the activation of inhibitor of kappa B alpha(IκBα)and expression of IL-1β.The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK2 inhibitor IV or IL-1R antagonists.●CONCLUSION:Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins,as well as the expression of IL-1β.These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium.

Repeated measurement of growth-differentiation factor-15in Chinese Han patients with post-myocardial infarction chronic heart failure

Background Growth-differentiation factor-15(GDF-15)is a promising prognostic biomarker in patients with chronic heart failure (CHF).Comparatively little is known about the value of repeated measurement of GDF-15with CI-IF in Chinese Han population.This study sought to identify the clinical value of repeated measurement of GDF-15in Chinese Han patients with post-myocardial infarction CHF. Methods In total,232consecutive Chinese Hart patients with post-myocardial infarction CHF were enrolled prospectively from January 2014to June 2016.The plasma concentration of GDF-15was determined on admission and over 12months.Patients were followed up for all-cause death and a composite outcome of major adverse cardiac events (MACE)included all-cause death,myocardial infarction and first heart failure (HF)re-hospitalization.Association with other clinical variables and adverse outcomes of repeated measurement of GDF-15 was explored.Results The median baseline GDF-15level was 2025ng/L.Baseline GDF-15was moderately associated with baseline N-terminal pro-B type nalriuretic peptide (NT-proBNP)(coefficient 0.561,P <0.001).During a median follow-up of 20months,there were 53deaths and 100MACE.GDF-I5remained an independent predictor of all-cause death (adjusted hazard ratio 1.826per 1Ln U,95%CI: 1.037-8.360;P =0.037)and MACE (adjusted hazard ratio 2.243per I Ln U,95%CI:1.181-1.775;P <0.001)adjusted for established risk factors.Repeated measurement of GDF-15was performed in 173survivals over 12months.Increase of GDF-15over 12months was associ- ated with dilatation of left ventricle and acted as an independent predictor of subsequent all-canse death (adjusted HR =3.164,95%CI: 1.245~.041;P =0.015).In the joint model,GDF-15was also shown to be a risk factor for all-cause death (HR =2.749,95%CI: 1.667-3.831;P <0.001)and MACE (FIR =2.434,95%CI:1.425-3.443;P <0.001).Conclusions Repeated measurements of GDF-15 have promising prognostic value of the risk of all-cause death in Chinese Han patients with CI-IF post-myocardial infarction.GDF-15may influence the post-myocardial infarction CI-IF through the path physiological pathway of myocardial remodeling.

Assessing inflammation in Chinese subjects with subtypes of heart failure: an observational study of the Chinese PLA Hospital Heart Failure Registry

Background Inflammation is an important element of the pathophysiological process of heart failure (HF) and is correlated with subtypes of HF. The association between multiple biomarkers of inflammation and HF subtypes in Chinese subjects remains unclear. This study aimed to compare the differences in inflammation biomarkers among Chinese patients with different subtypes of HF who have been identified to date. Methods We included 413 consecutive patients with HF,including 262 with preserved ejection fraction (HFpEF),55 with middle-ranged ejection fraction (HFmrEF) and 96 with reduced ejection fraction (HFrEF). Ten inflammation biomarkers were analyzed and compared according to the HF subtypes. One hundred contemporary non-HF subjects were also recruited as the control group. Moreover,the correlations between the inflammatory biomarkers and left ventricular ejection fraction of the HF subtypes were assessed. Results The mean age of the HF patients was 65.0 ± 12.0 years,65.8% were male. Distinct subtypes of HF demonstrated different inflammation biomarker panels. IL-6,PTX-3,ANGPTL-4 and TNF-α were correlated with HFrEF;IL-1β and PTX-3 were correlated with HFmrEF;and IL-1β and IL-6 were correlated with HFpEF. The multivariable logistic regression showed that IL-1β[relative ratio (RR)= 1.08,95% CI: 1.02–1.15,P = 0.010],IL-6 (RR = 1.03,95% CI: 1.01–1.06,P = 0.016),PTX-3 (RR = 1.31,95% CI: 1.11–1.55,P = 0.001),and ANGPTL-4 (RR = 1.05,95% CI: 1.02–1.07,P < 0.001) were independently associated with HF,while IL-6 (RR = 1.03,95% CI: 1.01–1.04,P = 0.019),PTX-3 (RR = 1.23,95% CI: 1.06–1.43,P = 0.007),and ANGPTL-4 (RR = 1.03,95% CI: 1.01–1.06,P = 0.005) were independently associated with the HF subtype. Conclusions Diverse inflammation biomarkers have multifaceted presentations according to the subtype of HF,which may illustrate the diverse mechanisms of inflammation in Chinese HF patients. IL-6,PTX-3,and ANGPTL-4 were independent inflammation factors associated with HFrEF and HF.

Fecal microbial dysbiosis in Chinese patients with inflammatory bowel disease

AIM To analyze the alterations of fecal microbiota in Chinese patients with inflammatory bowel disease(IBD).METHODS Fecal samples from 15 patients with Crohn's disease(CD)(11 active CD, 4 inactive CD), 14 patients with active ulcerative colitis(UC) and 13 healthy individuals were collected and subjected to 16 S ribosomal DNA(rDNA) gene sequencing. The V4 hypervariable regions of 16 S rDNA gene were amplified from all samples and sequenced by the Illumina Mi Seq platform. Quality control and operational taxonomic units classification of reads were calculated with QIIME software. Alpha diversity and beta diversity were displayed with R software.RESULTS Community richness(chao) and microbial structure in both CD and UC were significantly different from those in normal controls. At the phyla level, analysis of the microbial compositions revealed a significantly greater abundance of Proteobacteria in IBD as compared to that in controls. At the genera level, 8 genera in CD and 23 genera in UC(in particular, the Escherichia genus) showed significantly greater abundance as compared to that in normal controls. The relative abundance of Bacteroidetes in the active CD group was markedly lower than that in the inactive CD group. The abundance of Proteobacteria in patients with active CD was nominally higher than that in patients with inactive CD; however, the difference was not statistically significant after correction. Furthermore, the relative abundance of Bacteroidetes showed a negative correlation with the CD activity index scores.CONCLUSION Our study profiles specific characteristics and microbial dysbiosis in the gut of Chinese patients with IBD. Bacteroidetes may have a negative impact on inflammatory development.

Characterization of a Chinese KCNQ1 mutation （R259H） that shortens repolarization and causes short QT syndrome 2

ObjectivesTo 评估在一个 KCNQ1 变化， R259H，和短 QT 症候群(SQTS ) 之间并且到的协会探索位于他们的 association.MethodsWe 下面的机制执行了在 25 probands 和他们的家庭成员(63 个病人) 的 SQTS 基因的基因屏蔽的 electrophysiological。我们使用了屏蔽编码贡献室的行动潜力的极化的离子隧道的候选人基因的 exons 和 intron-exon 边界的直接定序，包括 KCNQ1， KCNH2， KCNE1， KCNE2， KCNJ2， CACNA1c， CACNB2b 和 CACNA2D1。在屏蔽的 25 SQTS probands 之一，我们发现了一个 KCNQ1 变化， R259H。我们克隆 R259H 并且短暂地在 HEK-293 房间表示了它；然后，水流用整个房间补丁被记录夹钳显著地显示出的 techniques.ResultsR259H-KCNQ1 增加了当前的密度，它在在 1 s 的动摇脉搏以后是近似比野类型(WT ) 的大的 3 褶层。激活和 inactivation 的稳定的州的电压依赖没显示出 WT 和 R259H 变化之间的重要差别(P >；0.05 ) 而释放的时间常数显著地以测试潜力与 WT 相比在异种被延长，它显示 R259H 的释放比 WT 的显著地慢。这些结果建议 R259H 变化罐头有效地增加慢慢地激活的推迟的整流器钾电流(我 K ) 在分阶段执行 3 心脏的行动潜力，它可以是 QT 间隔 shortening.ConclusionsR259H 的一个很少发生的原因是为 SQTS2 负责的 KCNQ1 隧道的一个 gain-of-function 变化。这是 R259H 变化在中国人民被检测的第一次。

Efficacy and economic benefits of a modified Valsalva maneuver in patients with paroxysmal supraventricular tachycardia

BACKGROUND A modified Valsalva maneuver(VM)has been suggested to be superior to the standard VM for conversion of paroxysmal supraventricular tachycardia(PSVT).AIM To evaluate the efficacy and economic benefits of a modified VM in Chinese patients.METHODS Patients with PSVT admitted to our center between October 2017 and September 2019 were randomly assigned to the modified and standard VM groups.Conversion via VM was performed up to three times.The primary outcome of the study was the success rate of PSVT conversion to sinus rhythm.The secondary outcomes included the incidence of adverse events,economic cost during the visit,and the degree of patient acceptance of the treatment.RESULTS Overall,361 patients were enrolled,with 180 allocated to the modified VM group and 181 to the standard VM group.Baseline characteristics were well matched in the groups.Overall,the modified VM group had higher success rates of PSVT conversion after single(47.78%vs 15.38%,P<0.001)and multiple(62.22%vs 19.78%,P<0.001)VM sessions.No significant differences in the incidences of adverse events and rates of patient acceptance were detected between the two groups(both P>0.05).Moreover,the economic cost of the clinic visit was significantly lower for the modified VM group than for the standard VM group(P<0.05).CONCLUSION The modified VM may confer both therapeutic and economic benefits as compared with the standard VM for conversion of PSVT.

Serological investigation of IgG and IgE antibodies against food antigens in patients with inflammatory bowel disease

BACKGROUND Food antigens have been shown to participate in the etiopathogenesis of inflammatory bowel disease (IBD),but their clinical value in IBD is still unclear.AIM To analyze the levels of specific immunoglobulin G (IgG) and E (IgE) antibodies against food antigens in IBD patients and to determine their clinical value in the pathogenesis of IBD.METHODS We performed a retrospective study based on patients who visited the First Affiliated Hospital of Nanjing Medical University between August 2016 and January 2018.A total of 137 IBD patients,including 40 patients with ulcerative colitis (UC) and 97 patients with Crohn’s disease (CD),and 50 healthy controls (HCs),were recruited.Serum food-specific IgG antibodies were detected by semiquantitative enzyme-linked immunosorbent assay,and serum food-specific IgE antibodies were measured by Western blot.The value of food-specific IgG antibodies was compared among different groups,and potent factors related to these antibodies were explored by binary logistic regression.RESULTS Food-specific IgG antibodies were detected in 57.5% of UC patients,in 90.72% of CD patients and in 42% of HCs.A significantly high prevalence and titer of foodspecific IgG antibodies were observed in CD patients compared to UC patients and HCs.The number of IgG-positive foods was greater in CD and UC patients than in HCs (CD vs HCs,P = 0.000;UC vs HCs,P = 0.029).The top five food antigens that caused positive specific IgG antibodies in CD patients were tomato (80.68%),corn (69.32%),egg (63.64%),rice (61.36%),and soybean (46.59%).The foods that caused positive specific IgG antibodies in UC patients were egg (60.87%),corn (47.83%),tomato (47.83%),rice (26.09%),and soybean (21.74%).Significantly higher levels of total food-specific IgG were detected in IBD patients treated with anti-TNFα therapy compared to patients receiving steroids and immunosuppressants (anti-TNFα vs steroids,P = 0.000;anti-TNFα vs immunosuppressants,P = 0.000;anti-TNFα vs steroids + immunosuppressants,P = 0.003).A decrease in food-specific IgG levels was detected in IBD patients after receiving anti-TNFα therapy (P = 0.007).Patients who smoked and CD patients were prone to developing serum food-specific IgG antibodies [Smoke: OR (95%CI): 17.6 (1.91-162.26),P = 0.011;CD patients: OR (95%CI): 12.48 (3.45-45.09),P = 0.000].There was no difference in the prevalence of food-specific IgE antibodies among CD patients (57.1%),UC patients (65.2%) and HCs (60%)(P = 0.831).CONCLUSION CD patients have a higher prevalence of food-specific IgG antibodies than UC patients and HCs.IBD patients are prone to rice,corn,tomato and soybean intolerance.Smoking may be a risk factor in the occurrence of food-specific IgG antibodies.Food-specific IgG antibodies may be a potential method in the diagnosis and management of food intolerance in IBD.

Effects of allitridum on the transient outward potassium current in rats with heart failure

在短暂的外面的钾水流上学习 allitridum 的效果(我 到在心失败(HF ) 的室的 myocytes 的 ).MethodsThe 双酶的方法被用来把单个室的 myocytes 与 Sprague Dawley 老鼠分开。夹钳补丁习惯于记录我 到 和分析 current.ResultsThe 上的 allitridum 的效果我 到 ，电流在 HF 组有重要减少，与控制组相比。密度我 到在 HF 的 ，组在 allitridum 的处理以后被增加(30 ????????? 佐 ??? 啓位 ??? 潃据畬楳湯即偎？？

Tranilast inhibits TGF-β-induced collagen gel contraction mediated by human corneal fibroblasts

AIM： To determine if tranilast affects human corneal fibroblast（HCFs） contraction.METHODS： HCFs cultured in a three-dimensional type I collagen gel were treated with or without transforming growth factor beta（TGF-β） or tranilast. Gel diameter was measured as an indicator for collagen contraction. Immunoblot was performed to evaluate myosin light chain（MLC） and paxillin phosphorylation. Confocal microscopy was employed to examine the focal adhesions and actin stress fiber formation. Immunoblot analysis and gelatin zymography were performed to detect tissue inhibitors of metalloproteinases and matrix metalloproteinases（MMPs） in supernatant.RESULTS： The inhibitory effect of tranilast on HCFsmediated collagen gel contraction induced by TGF-β was dose-dependent. The significant effect of tranilast was started from 100 μmol/L and maximized at 300 μmol/L. The peak effect of 300 μmol/L tranilast also relied on the duration of treatment, which showed statistical significance from day 2. TGF-β-induced paxillin and MLC phosphorylation, stress fiber formation, focal adhesions, and MMP-1, MMP-2, and MMP-3 secretion in HCFs were also inhibited by tranilast.CONCLUSION： Tranilast suppresses the HCFs-cultured collagen gel contraction induced by TGF-β. It attenuates actin stress fibers formation, focal adhesions, and the secretion of MMPs, with these actions likely contributing to the inhibitory effect on HCF contractility. By attenuating the contractility of corneal fibroblasts, tranilast treatment may inhibit corneal scarring.

Mantle cell lymphoma with endobronchial involvement:A case report

BACKGROUND Mantle cell lymphoma(MCL)is a subtype of Non-Hodgkin’s lymphoma(NHL).MCL frequently affects extranodal sites while endobronchial involvement is uncommon.Only 5 cases of MCL with endobronchial involvement have been previously reported.CASE SUMMARY A 56-year-old male patient arrived at the hospital complaining of a dry cough.A mass in the right upper lobe of the lung was revealed in Chest computed tomography(CT).Right lung hilar and mediastinal lymphadenopathies were also found by CT scan.The patient was diagnosed with central-type lung cancer with multiple lymph node metastases after positron emission tomography(PET)CT scan examination.The fiber optic bronchoscope examination revealed diffuse neoplasm infiltration in the inlet of the right up lobar bronchus.The patient was finally diagnosed with MCL based on the bronchoscopy and mediastinoscopy biopsy results.CONCLUSION MCL could masquerade as central type lung cancer.An endobronchial biopsy examination is necessary for the early diagnosis of MCL.

Consensus statement on layout and delivery of automatic external defibrillator in China

1.Introduction Sudden cardiac death(SCD)refers to sudden death due to a variety of cardiac causes.It is manifested as a sudden loss of consciousness,cardiac arrest,and respiratory arrest and generally shows early symptoms that are atypical and not easily detected[1].According to a recent study,nearly 544000 patients suffer from SCD every year in China[2].

Association of COL1A1 polymorphism with high myopia: a Meta-analysis

AIM： To investigate the association between collagen type I alpha 1（COL1A1） gene and high myopia.· METHODS： In this Meta-analysis, we examined 5published case-control studies that involved 1942 high myopia cases and 2929 healthy controls to assess the association between the COL1A1 rs2075555 polymorphism and high myopia risk. We calculated the pooled odds ratios（ORs） of COL1A1 rs2075555 polymorphism in high myopia cases vs healthy controls to evaluate the strength of the association.·RESULTS： Overall, there was no significant difference both in the genotype and allele distributions of COL1A1rs2075555 polymorphism between high myopia cases and healthy controls： CC vs AA OR =1.10, 95% confidence interval（CI）=0.76-1.58; AC vs AA OR=0.98, 95%CI 0.80-1.20; CC/AC vs AA/OR=1.01, 95%CI 0.84-1.22; CC vs AC/AA OR =1.06, 95% CI =0.93-1.20; C vs A OR =1.06, 95% CI0.91-1.23）. In addition, in the stratified analyses by ethnicity, no significant associations were found in any genetic model both in European and Asia cohorts.·CONCLUSION： Our results indicate that the COL1A1rs2075555 polymorphism may not affect susceptibility to high myopia.

β-receptor blocker influences return of spontaneous circulation and chemical examination in rats during cardiopulmonary resuscitation

Objective:We investigated the influence of β-receptor blocker metoprolol on return of spontaneous circulation(ROSC) during cardiopulmonary resuscitation(CPR) in rats with induced myocardial infarction(MI).Methods:Male Sprague-Dawley rats were randomly divided into three groups:the sham-operated group,the MI group without metoprolol,which was fed the vehicle,and the MI+metoprolol group receiving intragastric metoprolol.Each group was further divided randomly into three subgroups,depending on the dosage of epinephrine administered during subsequent CPR applied after the induction of asphyxial cardiac arrest.Results:The ROSC rate was significantly decreased in the low dose subgroup of MI group,unchanged in the medium dose subgroup of MI group,and significantly decreased in the high dose subgroup of MI group,compared with the same dose subgroup of sham-operated group.MI+metoprolol group had a lower ROSC rate than MI group in the medium dose subgroup,and a higher ROSC rate than MI group in the high dose subgroup.There was no difference in blood K+ values of successful rats between MI group and MI+metoprolol group.The rats with successful CPR had lower blood K+ values than rats with unsuccessful CPR in each of the three treatment groups.Conclusions:Metoprolol administered to MI rats over a long period significantly improved ROSC rates under an appropriate dose of epinephrine during CPR.An increasing high blood K+ value would attenuate the rate of a successful CPR.

Oxidative intramolecular coupling of 2,3-disubstituted phenyl acrylic acids and derivatives promoted by di-tert-butylperoxide

Polymethoxy-substituted phenanthrene-9-carboxylic acids or their methylate are key intermediates for the synthesis of tylophora alkaloids and their analogs. An intramolecular oxidative coupling reaction of unfunctionalized 2,3-disubstituted phenyl acrylic acids and derivatives promoted by di-tert-butylper- oxide gave above intermediates in high yields. The mild reaction conditions and easy purification procedures of this method provide a new approach for the synthesis of phenanthrenes.

The effects of surface ligands and counter cations on the stability of anionic thiolated M_(12)Ag_(32)(M=Au,Ag) nanoclusters

The stabilities of [M12Ag32（SR）30]4- （M = Ag, Au and SR = SPhF2, SPhCF3, SPhF） clusters having the same structure but different surface ligands or counter cations were systematically studied. It was clearly revealed that a subtle structural change in the surface ligands or counter cations could significantly alter the overall stability of [M12Ag32（SR）30]4 although they all had an electronic structure of 18-electron superatom shell closure. SPhF2 was found as a better surface ligand than SPhCF3 or SPhF to stabilize [M12Ag32（SR）30]4-. And the use of more bulky [（PPhj）2N]＋ as the counter cations was revealed to be more deleterious to the overall stability of [M12Ag32（SR）30]4- clusters than PPh4＋. [Au12Ag32（SR）30]4- was much more stable than [Ag44（SR）30]4 with the same surface ligands and counter cations. An exceptional stability was observed on （PPh4）4[Au12Ag32（SPhF2）30] which was stable in DMF for more than 8 days in air at 80 ℃. More research efforts are still needed to deeply understand why a small structural change could result in a significant change in the stability of noble metal nanoclusters.