Bioinformatic analysis for the identification of potential gene interactions and therapeutic targets in atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) is the most common type of tachycardia. The major injury caused by AF is a systemic embolism. Although AF therapies have evolved substantially, the success rate of sinus rhythm maintenance is relatively low. The reason is the incomplete understanding of the AF mechanisms. MATERIALS AND METHODS: A Gene Expression Omnibus (GEO) dataset (GSE79768) was downloaded. Differentially expressed genes (DEGs) were identified by bioinformatic analysis. Enriched terms and pathways were identified by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was constructed to determine regulatory genes. CytoHubba and the Molecular Complex Detection (MCODE) algorithm were used to identify potential hub genes and important modules. The Predicting Associated Transcription Factors From Annotated Affinities (PASTAA) method was used to predict transcription factors (TFs). RESULTS: Two hundred thirty-five upregulated DEGs and seventy-seven downregulated DEGs were identified. In the GO biological process, cellular component, and molecular function analyses, positive regulation of cell migration, anchoring junctions, and cell adhesion molecule binding were enriched significantly. The Hippo signalling pathway was the most significantly enriched pathway. In the PPI network analysis, we found that Class A/1 (rhodopsin-like receptors) may be the critical module. Ten hub genes were extracted, including 6 upregulated genes and 4 downregulated genes. CXCR2, TLR4, and CXCR4 may play critical roles in AF. In the TF prediction, we found that Irf-1 may be implicated in AF. CONCLUSIONS: We found that the CXCR4, TLR4, CXCR2 genes, the Hippo signalling pathway and the class A/1 (rhodopsin-like receptors) module may play critical roles in AF occurrence and maintenance, which may provide novel targets for AF treatment.

Significant difference of neutrophil-lymphocyte ratio between colorectal cancer, adenomatous polyp and healthy people.

OBJECTIVE: Tumor was reported to correlate with inflammation and the host's inflammatory response to tumor has been shown to independently predict the outcome. Many measures of the systemic inflammatory response have been studied in recent years. In the present study the full blood count (leukocyte, neutrophil, lymphocyte) of colorectal cancers (CRCs) adenomatous polyps, and healthy people were collected, and the difference of ratios was studied. PATIENTS AND METHODS: A total of 752 individuals (242 colorectal cancers, 248 adenomatous polyps, and 262 healthy people) were randomized enrolled in the present study. The full blood counts (leukocyte, neutrophil, and lymphocyte) of each individual were collected and the NLRs were calculated. RESULTS: The leukocyte count, neutrophil ratio and neutrophil-lymphocyte ratio were the highest in colorectal cancer group, the second in adenomatous polyp group, and the lowest in healthy control (p < 0.001). The lymphocyte ratio was in the reverse order (p < 0.001). The ROC curve analysis showed that sensitivity and specificity levels of NLR were 66.9% and 77.6% for CRCs, 36.7% and 80.9% for adenomatous polyp. The leukocyte count was higher in the advanced adenomatous polyp compared with low-risk group (p = 0.042). Further analyses of the diagnostic value of NLR are warranted in the future. CONCLUSIONS: Difference of leukocyte count, neutrophil ratio and NLR may provide available information in the differential diagnosis of CRC, adenomatous polyp and healthy people.

Assays to Monitor Lysophagy.

Lysophagy belongs to one of the many pathways cells activate in response to lysosomal damage. Damaged lysosomes attract glycan-binding galectins, become ubiquitinated, and are later on targeted for engulfment and degradation through lysophagy. Many triggers that are known to cause lysosomal membrane permeabilization have all been shown to induce lysophagy and can therefore be used to construct platforms for further molecular-level characterization of this process. In this chapter, we describe experimental parameters for triggering lysophagy through combined use of lysosome-specific dyes and light illumination. Within single cells, this optogenetic scheme allows easy manipulation on the amount of lysosomes to be impaired, the degree of damage desired, as well as when and where this should happen. On the other hand it can also be used to target all lysosomes within the entire cell population of a culture, allowing screening or bulk biochemical analyses to be carried out. The methodology will find use not only in monitoring lysophagy but also in probing lysosome damage responses in general.

Atrial fibrillation patients who sustained warfarin-associated intracerebral haemorrhage have poor neurological outcomes: results from a matched case series.

INTRODUCTION: Coagulopathy-associated intracerebral haemorrhage has become increasingly common because of the rising demand in the ageing population for anticoagulation for atrial fibrillation. This study compared the clinical features and neurological outcomes of intracerebral haemorrhage in patients with atrial fibrillation who were prescribed warfarin with those who were not. METHODS: This was a retrospective matched case series of patients with intracerebral haemorrhage from three tertiary hospitals in Hong Kong from 1 January 2006 to 31 December 2011. Patients who developed intracerebral haemorrhage and who were prescribed warfarin for atrial fibrillation (ICH-W group) were compared with those with intracerebral haemorrhage and not prescribed warfarin (ICH-C group); they were matched for age and gender in 1:1 ratio. Clinical features and neurological outcomes were compared, and the impact of coagulopathy on haematoma size was also studied. RESULTS: We identified 114 patients in the ICH-W group with a mean age of 75 years. Both ICH-W and ICH-C groups had a median intracerebral haemorrhage score of 2. There was a non-statistically significant trend of higher intracerebral haemorrhage volume in the ICH-W group (12.9 mL vs 10.5 mL). The median modified Rankin Scale and the proportion with good recovery (modified Rankin Scale score ≤3) at 6 months were comparable. Nonetheless, ICH-W patients had higher hospital mortality (51.8% vs 36.0%; P=0.02) and 6-month mortality (60.5% vs 43.0%; P=0.01) than ICH-C patients. Overall, 60% of ICH-W patients had their admission international normalised ratio within the therapeutic range during intracerebral haemorrhage, and 14% had a subtherapeutic admission international normalised ratio. International normalised ratio at admission was not associated with intracerebral haemorrhage volume or neurological outcome. CONCLUSION: Warfarin-associated intracerebral haemorrhage in patients with atrial fibrillation carried a higher stroke mortality than the non-warfarinised patients.

Study of e(+)e(-)→ωχ(cJ) at center of mass energies from 4.21 to 4.42 GeV.

Based on data samples collected with the BESIII detector at the BEPCII collider at nine center of mass energies from 4.21 to 4.42 GeV, we search for the production of e^{+}e^{-}→ωχ_{cJ} (J=0, 1, 2). The process e^{+}e^{-}→ωχ_{c0} is observed for the first time, and the Born cross sections at sqrt[s]=4.23 and 4.26 GeV are measured to be (55.4±6.0±5.9) and (23.7±5.3±3.5) pb, respectively, where the first uncertainties are statistical and the second are systematic. The ωχ_{c0} signals at the other seven energies and the e^{+}e^{-}→ωχ_{c1} and ωχ_{c2} signals are not significant, and the upper limits on the cross sections are determined. By examining the ωχ_{c0} cross section as a function of center of mass energy, we find that it is inconsistent with the line shape of the Y(4260) observed in e^{+}e^{-}→π^{+}π^{-}J/ψ. Assuming the ωχ_{c0} signals come from a single resonance, we extract the mass and width of the resonance to be (4230±8±6) MeV/c^{2} and (38±12±2) MeV, respectively, and the statistical significance is more than 9σ.

Observation of e(+)e(-)→π(0)π(0)hc and a neutral charmoniumlike structure Zc(4020)(0).

Using data collected with the BESIII detector operating at the Beijing Electron Positron Collider at center-of-mass energies of sqrt[s]=4.23, 4.26, and 4.36 GeV, we observe e(+)e(-)→π(0)π(0)hc for the first time. The Born cross sections are measured and found to be about half of those of e(+)e(-)→π(+)π(-)hc within less than 2σ. In the π(0)hc mass spectrum, a structure at 4.02 GeV/c(2) is found. It is most likely to be the neutral isospin partner of the Zc(4020)(±) observed in the process of e(+)e(-)→π(+)π(-)hc being found. A fit to the π(0)hc invariant mass spectrum, with the width of the Zc(4020)(0) fixed to that of its charged isospin partner and possible interferences with non-Zc(4020)(0) amplitudes neglected, gives a mass of (4023.9±2.2±3.8) MeV/c(2) for the Zc(4020)(0), where the first error is statistical and the second systematic.

The value of comparing mortality of Guillain-Barré syndrome across different regions.

OBJECTIVE: To study the clinical profile of Guillain-Barré syndrome (GBS) patients who died in 4 Asian countries in order to understand factors underlying any variation in mortality. METHODS: Retrospectively reviewed medical records of GBS patients who died in 7 hospitals from 4 Asian countries between 2001 and 2012. Baseline characteristics, timing and causes of death were recorded. RESULTS: A total of 16 out of 261 GBS patients died. The overall mortality rate was 6%, with a range of 0 to 13%. The leading causes of death were respiratory infections, followed by myocardial infarction. The median age of our patients was 77 years. Half of the patients required mechanical ventilation and almost all had significant concomitant illnesses. A disproportionate number of patients in the Hong Kong cohort died (13%). Patients with advanced age, fewer antecedent respiratory infections and need for mechanical ventilation were at most risk. Most deaths occurred during the plateau phase of GBS and on the general ward after having initially received intensive care. CONCLUSIONS: There is considerable variability in mortality of GBS among different Asian cohorts. Although the risks factors for mortality were similar to Western cohorts, the timing and site of death differed. This allows specific measures to be implemented to improve GBS care in countries with higher mortality.

Observation of η'→π+ π π+ π- and η'→π+π- π0 π0.

Using a sample of 1.3 × 10(9) J/ψ events collected with the BESIII detector, we report the first observation of η(')→π(+)π(-)π(+)π(-) and η(')→π(+)π(-)π(0)π(0). The measured branching fractions are B(η(')→π(+)π(-)π(+)π(-)) = [8.53 ± 0.69(stat.) ± 0.64(syst.)]×10(-5) and B(η(')→π(+)π(-)π(0) π(0)) = [1.82 ± 0.35(stat.) ± 0.18(syst.)] × 10(-4), which are consistent with theoretical predictions based on a combination of chiral perturbation theory and vector-meson dominance.

Observation of a charged charmoniumlike structure in e+ e- → (D* D*)± π∓ at √s = 4.26 GeV.

We study the process e+ e- →(D* D*)± π∓ at a center-of-mass energy of 4.26 GeV using a 827 pb(-1) data sample obtained with the BESIII detector at the Beijing Electron Positron Collider. Based on a partial reconstruction technique, the Born cross section is measured to be (137±9±15) pb. We observe a structure near the (D* D*)± threshold in the π∓ recoil mass spectrum, which we denote as the Zc±(4025). The measured mass and width of the structure are (4026.3±2.6±3.7) MeV/c2 and (24.8±5.6±7.7) MeV, respectively. Its production ratio σ(e+ e- → Zc±(4025)π∓ → (D* D*)± π∓)/σ(e+ e- → (D* D*)± π∓) is determined to be 0.65±0.09±0.06. The first uncertainties are statistical and the second are systematic.

Observation of e+e- → γX(3872) at BESIII.

With data samples collected with the BESIII detector operating at the BEPCII storage ring at center-of-mass energies from 4.009 to 4.420 GeV, the process e+e-→ γX(3872) is observed for the first time with a statistical significance of 6.3σ. The measured mass of the X(3872) is (3871.9 ± 0.7s tat ± 0.2 syst) MeV/c(2), in agreement with previous measurements. Measurements of the product of the cross section σ[e+e- → γX(3872)] and the branching fraction B[X(3872)→π+π-J/ψ] at center-of-mass energies 4.009, 4.229, 4.260, and 4.360 GeV are reported. Our measurements are consistent with expectations for the radiative transition process Y(4260) → γX(3872).

Observation of a charged (DD*)± mass peak in e+ e- → πDD* at sqrt[s] = 4.26 GeV.

We report on a study of the process e+ e- → π± (DD*)∓ at sqrt[s] = 4.26 GeV using a 525 pb(-1) data sample collected with the BESIII detector at the BEPCII storage ring. A distinct charged structure is observed in the (DD*)∓ invariant mass distribution. When fitted to a mass-dependent-width Breit-Wigner line shape, the pole mass and width are determined to be Mpole = (3883.9±1.5(stat)±4.2(syst)) MeV/c2 and Γpole = (24.8±3.3(stat)±11.0(syst)) MeV. The mass and width of the structure, which we refer to as Zc(3885), are 2σ and 1σ, respectively, below those of the Zc(3900) → π± J/ψ peak observed by BESIII and Belle in π+ π- J/ψ final states produced at the same center-of-mass energy. The angular distribution of the πZc(3885) system favors a JP = 1+ quantum number assignment for the structure and disfavors 1- or 0-. The Born cross section times the DD* branching fraction of the Zc(3885) is measured to be σ(e+ e- → π± Zc(3885)∓)×B(Zc(3885)∓ → (DD*)∓) = (83.5±6.6(stat)±22.0(syst)) pb. Assuming the Zc(3885) → DD* signal reported here and the Zc(3900) → πJ/ψ signal are from the same source, the partial width ratio (Γ(Zc(3885) → DD*)/Γ(Zc(3900) → πJ/ψ)) = 6.2±1.1(stat)±2.7(syst) is determined.

Observation of a charged charmoniumlike structure in e+ e- → π+ π- J/ψ at sqrt[s] = 4.26 GeV.

We study the process ee+ e- → π+ π- J/ψ at a center-of-mass energy of 4.260 GeV using a 525 pb(-1) data sample collected with the BESIII detector operating at the Beijing Electron Positron Collider. The Born cross section is measured to be (62.9±1.9±3.7) pb, consistent with the production of the Y(4260). We observe a structure at around 3.9 GeV/c2 in the π(±)J/ψ mass spectrum, which we refer to as the Z(c)(3900). If interpreted as a new particle, it is unusual in that it carries an electric charge and couples to charmonium. A fit to the π(±)J/ψ invariant mass spectrum, neglecting interference, results in a mass of (3899.0±3.6±4.9) MeV/c2 and a width of (46±10±20) MeV. Its production ratio is measured to be R = (σ(e+ e- → π(±)Z(c)(3900)(∓) → π+ π- J/ψ)/σ(e+ e- → π+ π- J/ψ)) = (21.5±3.3±7.5)%. In all measurements the first errors are statistical and the second are systematic.

Observation of two new N* resonances in the decay ψ(3686)→ppπ0.

Based on 106×10(6)ψ(3686) events collected with the BESIII detector at the BEPCII facility, a partial wave analysis of ψ(3686)→ppπ0 is performed. The branching fraction of this channel has been determined to be B(ψ(3686)→ppπ0)=(1.65±0.03±0.15)×10(-4). In this decay, 7 N* intermediate resonances are observed. Among these, two new resonances, N(2300) and N(2570) are significant, one 1/2+ resonance with a mass of 2300(-30-0)(+40+109) MeV/c2 and width of 340(-30-58)(+30+110) MeV/c2, and one 5/2- resonance with a mass of 2570(-10-10)(+19+34) MeV/c2 and width of 250(-24-21)(+14+69) MeV/c2. For the remaining 5 N* intermediate resonances [N(1440), N(1520), N(1535), N(1650) and N(1720)], the analysis yields mass and width values that are consistent with those from established resonances.

Observation of a charged charmoniumlike structure Zc(4020) and search for the Zc(3900) in e+e-→π+π-hc.

We study e+e-→π+π-hc at center-of-mass energies from 3.90 to 4.42 GeV by using data samples collected with the BESIII detector operating at the Beijing Electron Positron Collider. The Born cross sections are measured at 13 energies and are found to be of the same order of magnitude as those of e+e-→π+π-J/ψ but with a different line shape. In the π±hc mass spectrum, a distinct structure, referred to as Zc(4020), is observed at 4.02 GeV/c2. The Zc(4020) carries an electric charge and couples to charmonium. A fit to the π±hc invariant mass spectrum, neglecting possible interferences, results in a mass of (4022.9±0.8±2.7) MeV/c2 and a width of (7.9±2.7±2.6) MeV for the Zc(4020), where the first errors are statistical and the second systematic. The difference between the parameters of this structure and the Zc(4025) observed in the D*D[over ¯]* final state is within 1.5σ, but whether they are the same state needs further investigation. No significant Zc(3900) signal is observed, and upper limits on the Zc(3900) production cross sections in π±hc at center-of-mass energies of 4.23 and 4.26 GeV are set.

Evidence for the direct two-photon transition from ψ(3686) to J/ψ.

The two-photon transition ψ(3686)→γγJ/ψ is studied in a sample of 1.06×10(8) ψ(3686) decays collected by the BESIII detector. The branching fraction is measured to be (3.1±0.6(stat)(-1.0)(+0.8)(syst))×10(-4) using J/ψ→e(+)e(-) and J/ψ→µ(+)µ(-) decays, and its upper limit is estimated to be 4.5×10(-4) at the 90% confidence level. This work represents the first measurement of a two-photon transition among charmonium states. The orientation of the ψ(3686) decay plane and the J/ψ polarization in this decay are also studied. In addition, the product branching fractions of sequential E1 transitions ψ(3686)→γχ(cJ) and χ(cJ)→γJ/ψ(J=0,1,2) are reported.

Measurements of the mass and width of the η(c) using the decay ψ(3686)→γη(c).

The mass and width of the lowest-lying S-wave spin singlet charmonium state, the η(c), are measured using a data sample of 1.06×10(8) ψ(3686) decays collected with the BESIII detector at the BEPCII storage ring. We use a model that incorporates full interference between the signal reaction, ψ(3686)→γη(c), and a nonresonant radiative background to describe the line shape of the η(c) successfully. We measure the η(c) mass to be 2984.3±0.6±0.6 MeV/c(2) and the total width to be 32.0±1.2±1.0 MeV, where the first errors are statistical and the second are systematic.

First observation of the M1 transition ψ(3686)→γη(c)(2S).

Using a sample of 106×10(6) ψ(3686) events collected with the BESIII detector at the BEPCII storage ring, we have made the first measurement of the M1 transition between the radially excited charmonium S-wave spin-triplet and the radially excited S-wave spin-singlet states: ψ(3686)→γη(c)(2S). Analyses of the processes ψ(3686)→γη(c)(2S) with η(c)(2S)→K(S)(0)K(±)π(∓) and K(+)K(-)π(0) give an η(c)(2S) signal with a statistical significance of greater than 10 standard deviations under a wide range of assumptions about the signal and background properties. The data are used to obtain measurements of the η(c)(2S) mass (M(η(c)(2S))=3637.6±2.9(stat)±1.6(syst) MeV/c(2)), width (Γ(η(c)(2S))=16.9±6.4(stat)±4.8(syst) MeV), and the product branching-fraction (B(ψ(3686)→γη(c)(2S))×B(η(c)(2S)→KKπ)=(1.30±0.20(stat)±0.30(syst))×10(-5)). Combining our result with a BABAR measurement of B(η(c)(2S)→KKπ), we find the branching fraction of the M1 transition to be B(ψ(3686)→γη(c)(2S))=(6.8±1.1(stat)±4.5(syst))×10(-4).

First observation of η(1405) decays into f(0)(980)π0.

The decays J/ψ → γ π+ π- π0 and J/ψ → γ π0 π0 π0 are analyzed using a sample of 225×10(6) J/ψ events collected with the BESIII detector. The decay of η(1405) → f(0)(980)π0 with a large isospin violation is observed for the first time. The width of the f(0)(980) observed in the dipion mass spectra is anomalously narrower than the world average. Decay rates for three-pion decays of the η' are also measured precisely.

Spin-parity analysis of pp¯ mass threshold structure in J/ψ and ψ(3686) radiative decays.

A partial wave analysis of the pp¯ mass-threshold enhancement in the reaction J/ψ→γpp¯ is used to determine its J(PC) quantum numbers to be 0(-+), its peak mass to be below threshold at M=1832(-5)(+19)(stat)(-17)(+18)(syst)±19(model) MeV/c(2), and its total width to be Γ<76 MeV/c(2) at the 90% C.L. The product of branching ratios is measured to be BR[J/ψ→γX(pp¯)]BR[X(pp¯)→pp¯]=[9.0(-1.1)(+0.4)(stat)(-5.0)(+1.5)(syst)±2.3(model)]×10(-5). A similar analysis performed on ψ(3686)→γpp¯ decays shows, for the first time, the presence of a corresponding enhancement with a production rate relative to that for J/ψ decays of R=[5.08(-0.45)(+0.71)(stat)(-3.58)(+0.67)(syst)±0.12(model)]%.

ηπ+ π- resonant structure around 1.8 GeV/c(2) and η(1405) in J/ψ → ωηπ+ π-.

We present results of a study of the decay J/ψ → ωηπ+ π- using a sample of (225.2 ± 2.8) × 10(6) J/ψ events collected by the BESIII detector, and report the observation of a new process J/ψ → ωX(1870) with a statistical significance of 7.2σ, in which X(1870) decays to a(0)(±)(980)π±. Fitting to ηπ+ π- mass spectrum yields a mass M = 1877.3 ± 6.3(stat)(-7.4)(+3.4)(syst) MeV/c(2), a width Γ = 57 ± 12(stat)(-4)(+19)(syst) MeV/c(2), and a product branching fraction B(J/ψ → ωX) × B(X→a(0)(±)(980)π±) × B(a(0) (±)(980) → ηπ±) = [1.50 ± 0.26(stat)(-0.36)(+0.72) (syst)] × 10(-4). Signals for J/ψ → ωf(1)(1285) and J/ψ → ω η(1405) are also clearly observed and measured.