134 research outputs found
Inhibition of miR-665 alleviates neuropathic pain by targeting SOCS1
Purpose: To investigate the effect of miR-665 in neuropathic pain and the possible molecular mechanism involved.Methods: A neuropathic pain model was established using chronic constriction injury (CCI) methods in Sprague Dawley (SD) rats. Mechanical and thermal hyperalgesia were measured using paw withdrawal threshold (PWT) and paw withdrawal latency (PWL), respectively. The inflammation response was determined by assessing the production of inflammation factors. The target relationship of miR-665 and suppressor of cytokine signaling 1 (SOCS1) was verified by luciferase assay.Results: In the CCI rat model, PWT and PWL decreased following treatment with miR-665 (p < 0.01). MiR-665 was elevated in the spinal cord and microglia of CCI rats at different time points (p < 0.01). Down-regulation of miR-665 increased PWT and PWL and inhibited the production of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in CCI rats (p < 0.01). Luciferase assay results indicate that SOCS1 was the target of miR-665 (p < 0.01). SOCS1 decreased in CCI rats (p < 0.01) after treatment with miR-665. MiR-665 negatively regulated the expression of SOCS1 (p < 0.01). Down-regulation of SOCS1 reversed the alleviating effect of decreased miR-665 on pain sensitivity and inflammationresponse (p < 0.01).Conclusion: Down-regulation of miR-665 alleviates neuropathic pain by targeting SOCS1, and hence making miR-665 a promising therapeutic target for neuropathic pain.
Keywords: MiR-665, SOCS1, Neuropathic pain, CCI, Spinal cor
Network-Based Gene Expression Biomarkers for Cold and Heat Patterns of Rheumatoid Arthritis in Traditional Chinese Medicine
In Traditional Chinese Medicine (TCM), patients with Rheumatoid Arthritis (RA) can be classified into two main patterns: cold-pattern and heat-pattern. This paper identified the network-based gene expression biomarkers for both cold- and heat-patterns of RA. Gene expression profilings of CD4+ T cells from cold-pattern RA patients, heat-pattern RA patients, and healthy volunteers were obtained using microarray. The differentially expressed genes and related networks were explored using DAVID, GeneSpring software, and the protein-protein interactions (PPI) method. EIF4A2, CCNT1, and IL7R, which were related to the up-regulation of cell proliferation and the Jak-STAT cascade, were significant gene biomarkers of the TCM cold pattern of RA. PRKAA1, HSPA8, and LSM6, which were related to fatty acid metabolism and the I-κB kinase/NF-κB cascade, were significant biomarkers of the TCM heat-pattern of RA. The network-based gene expression biomarkers for the TCM cold- and heat-patterns may be helpful for the further stratification of RA patients when deciding on interventions or clinical trials
Development and external validation of a prognostic multivariable model on admission for hospitalized patients with COVID-19
Summary Background COVID-19 pandemic has developed rapidly and the ability to stratify the most vulnerable patients is vital. However, routinely used severity scoring systems are often low on diagnosis, even in non-survivors. Therefore, clinical prediction models for mortality are urgently required. Methods We developed and internally validated a multivariable logistic regression model to predict inpatient mortality in COVID-19 positive patients using data collected retrospectively from Tongji Hospital, Wuhan (299 patients). External validation was conducted using a retrospective cohort from Jinyintan Hospital, Wuhan (145 patients). Nine variables commonly measured in these acute settings were considered for model development, including age, biomarkers and comorbidities. Backwards stepwise selection and bootstrap resampling were used for model development and internal validation. We assessed discrimination via the C statistic, and calibration using calibration-in-the-large, calibration slopes and plots. Findings The final model included age, lymphocyte count, lactate dehydrogenase and SpO 2 as independent predictors of mortality. Discrimination of the model was excellent in both internal (c=0·89) and external (c=0·98) validation. Internal calibration was excellent (calibration slope=1). External validation showed some over-prediction of risk in low-risk individuals and under-prediction of risk in high-risk individuals prior to recalibration. Recalibration of the intercept and slope led to excellent performance of the model in independent data. Interpretation COVID-19 is a new disease and behaves differently from common critical illnesses. This study provides a new prediction model to identify patients with lethal COVID-19. Its practical reliance on commonly available parameters should improve usage of limited healthcare resources and patient survival rate. Funding This study was supported by following funding: Key Research and Development Plan of Jiangsu Province (BE2018743 and BE2019749), National Institute for Health Research (NIHR) (PDF-2018-11-ST2-006), British Heart Foundation (BHF) (PG/16/65/32313) and Liverpool University Hospitals NHS Foundation Trust in UK. Research in context Evidence before this study Since the outbreak of COVID-19, there has been a pressing need for development of a prognostic tool that is easy for clinicians to use. Recently, a Lancet publication showed that in a cohort of 191 patients with COVID-19, age, SOFA score and D-dimer measurements were associated with mortality. No other publication involving prognostic factors or models has been identified to date. Added value of this study In our cohorts of 444 patients from two hospitals, SOFA scores were low in the majority of patients on admission. The relevance of D-dimer could not be verified, as it is not included in routine laboratory tests. In this study, we have established a multivariable clinical prediction model using a development cohort of 299 patients from one hospital. After backwards selection, four variables, including age, lymphocyte count, lactate dehydrogenase and SpO 2 remained in the model to predict mortality. This has been validated internally and externally with a cohort of 145 patients from a different hospital. Discrimination of the model was excellent in both internal (c=0·89) and external (c=0·98) validation. Calibration plots showed excellent agreement between predicted and observed probabilities of mortality after recalibration of the model to account for underlying differences in the risk profile of the datasets. This demonstrated that the model is able to make reliable predictions in patients from different hospitals. In addition, these variables agree with pathological mechanisms and the model is easy to use in all types of clinical settings. Implication of all the available evidence After further external validation in different countries the model will enable better risk stratification and more targeted management of patients with COVID-19. With the nomogram, this model that is based on readily available parameters can help clinicians to stratify COVID-19 patients on diagnosis to use limited healthcare resources effectively and improve patient outcome
Precise Measurements of Branching Fractions for Meson Decays to Two Pseudoscalar Mesons
We measure the branching fractions for seven two-body decays to
pseudo-scalar mesons, by analyzing data collected at
GeV with the BESIII detector at the BEPCII collider. The branching fractions
are determined to be ,
,
,
,
,
,
,
where the first uncertainties are statistical, the second are systematic, and
the third are from external input branching fraction of the normalization mode
. Precision of our measurements is significantly improved
compared with that of the current world average values
Observation of the Singly Cabibbo-Suppressed Decay
The singly Cabibbo-suppressed decay is observed for the first time with a statistical
significance of by using 4.5 fb of collision data
collected at center-of-mass energies between 4.600 and 4.699 GeV with the
BESIII detector at BEPCII. The absolute branching fraction of
is measured to be in a model-independent approach. This is
the first observation of a Cabibbo-suppressed decay involving
in the final state. The ratio of branching fractions between
and the Cabibbo-favored decay
is calculated to be , where with the
Cabibbo mixing angle. This ratio significantly deviates from and
provides important information for the understanding of nonfactorization
contributions in decays.Comment: 8 pages, 2 figure
Updated measurements of the M1 transition with
Based on a data sample of events
collected with the BESIII detector at the BEPCII collider, the M1 transition
with is
studied, where is or
. The mass and width of the are
measured to be MeV/
and MeV, respectively. The
product branching fraction is determined to be . Using , we obtain the branching fraction of the
radiative transition to be , where the third uncertainty is due to the quoted
Measurement of the cross sections from 2.000 to 3.080 GeV
Based on collision data collected at center-of-mass energies
from 2.000 to 3.080 GeV by the BESIII detector at the BEPCII collider, a
partial wave analysis is performed for the process . The results allow the Born cross sections of the process
, as well as its subprocesses
and to be
measured. The Born cross sections for are consistent with previous measurements by BaBar and SND,
but with substantially improved precision. The Born cross section lineshape of
the process is consistent with a vector
meson state around 2.2 GeV with a statistical significance of 3.2. A
Breit-Wigner fit determines its mass as
and its width as
, where the first uncertainties are
statistical and the second ones are systematic, respectively
Investigating the rule and CP violation through the measurement of decay asymmetry parameters in decays
Using events collected with the BESIII
detector, numerous and decay asymmetry parameters are
simultaneously determined from the process and its
charge-conjugate channel. The precisions of for
and for compared to world
averages are improved by factors of 4 and 1.7, respectively. The ratio of decay
asymmetry parameters of to that of ,
, is determined
to be , where the first and the second
uncertainties are statistical and systematic, respectively. The ratio is
smaller than unity, which is predicted by the rule, with a
statistical significance of more than . We test for CP violation in
and in with the best
precision to date.Comment: 8 pages, 2 figures, 1 tabl
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