Serum YKL-40 and Serum Krebs von den Lungen-6 as Potential Predictive Biomarkers for Rheumatoid Arthritis-Associated Interstitial Lung Disease.

BACKGROUND: Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis (RA) and is associated with a poor prognosis. However, the role of blood biomarkers in RA-associated interstitial lung disease (RA-ILD) is ill-defined. We aim to evaluate the role of YKL-40 and Krebs von den Lungen-6 (KL-6) in the diagnosis and severity evaluation of RA-ILD. METHODS: 45 RA-non-ILD patients and 38 RA-ILD patients were included. The clinical data and the levels of YKL-40 and KL-6 were measured and collected for all patients. The risk factors for RA-ILD were analyzed and their correlation with relevant indicators and predictive value for RA-ILD was explored. RESULTS: The levels of YKL-40 and KL-6 in RA-ILD patients were higher than RA-non-ILD patients (p < .001). Both YKL-40 and KL-6 were correlated with the incidence of RA-ILD. The predictive power of combined KL-6 and YKL-40 for the presence of ILD was 0.789, with a sensitivity and specificity at 73.7% and 73.3%, respectively. In RA-ILD patients, both YKL-40 and KL-6 were positively correlated with the Scleroderma Lung Study (SLS) I score and negatively correlated with pulmonary function. CONCLUSIONS: KL-6 and YKL-40 might be a useful biomarker in the diagnosis and severity evaluation of RA-ILD.

Changes of serum IgG glycosylation patterns in rheumatoid arthritis.

BACKGROUND: RA is a common chronic and systemic autoimmune disease, and the diagnosis is based significantly on autoantibody detection. This study aims to investigate the glycosylation profile of serum IgG in RA patients using high-throughput lectin microarray technology. METHOD: Lectin microarray containing 56 lectins was applied to detect and analyze the expression profile of serum IgG glycosylation in 214 RA patients, 150 disease controls (DC), and 100 healthy controls (HC). Significant differential glycan profiles between the groups of RA and DC/HC as well as RA subgroups were explored and verified by lectin blot technique. The prediction models were created to evaluate the feasibility of those candidate biomarkers. RESULTS: As a comprehensive analysis of lectin microarray and lectin blot, results showed that compare with HC or DC groups, serum IgG from RA patients had a higher affinity to the SBA lectin (recognizing glycan GalNAc). For RA subgroups, RA-seropositive group had higher affinities to the lectins of MNA-M (recognizing glycan mannose) and AAL (recognizing glycan fucose), and RA-ILD group had higher affinities to the lectins of ConA (recognizing glycan mannose) and MNA-M while a lower affinity to the PHA-E (recognizing glycan Galß4GlcNAc) lectin. The predicted models indicated corresponding feasibility of those biomarkers. CONCLUSION: Lectin microarray is an effective and reliable technique for analyzing multiple lectin-glycan interactions. RA, RA-seropositive, and RA-ILD patients exhibit distinct glycan profiles, respectively. Altered levels of glycosylation may be related to the pathogenesis of the disease, which could provide a direction for new biomarkers identification.

Randomized Pilot Study to Compare DCB-Based versus DST-Based Strategies for the Treatment of True or Complex Coronary Bifurcation Lesions.

Background: Dual stenting technique (DST) is still mandatory for some true bifurcation lesions (BLs), but drug-coated balloon (DCB) alone may offer a new optional treatment with the potential benefits of fewer implants. However, procedural safety presents a concern when using DCB-only to treat true BLs. This study sought to explore the safety and efficacy of the DCB-only strategy for the treatment of true BLs. Methods: Sixty patients with TBLs were randomly assigned to be treated by a DCB-based strategy or DST-based strategy. All patients received angiographic follow-up scheduled after one-year and staged clinical follow-up. The primary endpoint was the one-year late lumen loss (LLL) and cumulative major cardiac adverse events (MACEs) composed of cardiac death (CD), target vessel myocardial infarction (TVMI), target lesion thrombosis (TVT), or target vessel/lesion revascularization (TLR/TVR). The secondary endpoint was the one-year minimal lumen diameter (MLD), diameter stenosis percentage (DSP) or binary restenosis (BRS), and each MACE component. Results: The baseline clinical and lesioncharacteristics were comparable with similar proportions (20.0% vs. 23.3%, p = 1.000) of the complex BLs between the two groups. At the one-year follow-up, LLL was significantly lower in the DCB-based group (main-vessel: 0.05 ± 0.24 mm vs. 0.25 ± 0.35 mm, p = 0.013; side-branch: -0.02 ± 0.19 mm vs. 0.11 ± 0.15 mm, p = 0.005). MLD, DSP and TLR/TVR were comparable between the groups. The one-year cumulative MACE, all driven by TLR/TVR (6.7% vs. 13.3%, p = 0.667), was low and similar without CD, TVMI or TVT in both groups. Conclusions: Compared to the DST strategy, the DCB- based strategy may be safe and effective in treatment of the selected true BLs. Clinical Trial Registration: Clinical registration number is ChiCTR1900024914.

Tau acetylates and stabilizes ß-catenin thereby promoting cell survival.

Overexpressing Tau counteracts apoptosis and increases dephosphorylated ß-catenin levels, but the underlying mechanisms are elusive. Here, we show that Tau can directly and robustly acetylate ß-catenin at K49 in a concentration-, time-, and pH-dependent manner. ß-catenin K49 acetylation inhibits its phosphorylation and its ubiquitination-associated proteolysis, thus increasing ß-catenin protein levels. K49 acetylation further promotes nuclear translocation and the transcriptional activity of ß-catenin, and increases the expression of survival-promoting genes (bcl2 and survivin), counteracting apoptosis. Mutation of Tau's acetyltransferase domain or co-expressing non-acetylatable ß-catenin-K49R prevents increased ß-catenin signaling and abolishes the anti-apoptotic function of Tau. Our data reveal that Tau preserves ß-catenin by acetylating K49, and upregulated ß-catenin/survival signaling in turn mediates the anti-apoptotic effect of Tau.

Polydatin alleviates DSS- and TNBS-induced colitis by suppressing Th17 cell differentiation via directly inhibiting STAT3.

Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disease, often presenting with abdominal pain, diarrhea, bloody stool, anorexia, and body loss. It is difficult to cure completely and a promising treatment is urgently needed. Natural compounds can offer promising chemical agents for treatment of diseases. Polydatin is a natural ingredient extracted from the dried rhizome of Polygonum cuspidatum, which has anti-inflammatory, anti-tumor, and dementia protection activities. The purpose of this study was to evaluate the therapeutic effect of polydatin on IBD and explore its possible mechanism. We found that polydatin could effectively suppress the differentiation of Th17 cells in vitro, but had no effect on the differentiation of Treg cells. Polydatin significantly alleviated colitis induced by dextran sulfate sodium (DSS) and 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) in mice, and dramatically decreased the proportion of Th17 cells in spleen and mesenteric lymph nodes. Mechanism investigations revealed that polydatin specifically inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation by directly binding to STAT3, leading to Th17 cell reduction and thereby alleviating colitis. These findings provide novel insights into the anti-colitis effect of polydatin, which may be a promising drug candidate for the treatment of IBD.

Comparison of standard versus modified stenting technique for treatment of tapered coronary artery lesions.

Tapered coronary artery lesions (TCALs) are often seen clinically, optimal stenting of TCALs remains challengeable. This study sought to compare clinical outcomes between the modified single stenting (MSS) and conventional overlapped stenting (COS) in treatment of TCALs. 150 patients were treated with MSS (MSS group), another 150 patients were matched with propensity score matching from 5055 patients treated with COS (COS group). Quantitative coronary angiography was performed to measure minimal lumen diameter (MLD), late lumen loss (LLL). The primary endpoint was immediate angiographic success, one-year cumulative major cardiac adverse events (MACEs) composing cardiac death, target vessel myocardial infarction (TVMI), target lesion/vessel revascularization (TLR/TVR) or stent thrombosis (ST). Post-procedural in-stent MLD (2.96 ± 0.34 versus 3.08 ± 0.33, P = 0.004) was smaller and diameter stenosis (11.7 ± 4.0% versus 9.0 ± 4.8%, P = 0.003) was higher in MSS group than COS group. At 1-year follow-up, in-stent MLD (2.76 ± 0.38 mm versus 2.65 ± 0.60 mm, P = 0.003) was reduced, LLL (0.20 ± 0.26 mm versus 0.42 ± 0.48 mm, P = 0.001), diameter stenosis (24.02 ± 20.94% versus 19.68 ± 11.75%, P = 0.028) and binary restenosis (18.7% versus 10.0%, P = 0.047) were increased in COS group. Angiographic success (96.7% versus 98.0%, P = 0.723) was similar between MSS group and COS group. At 1-year, the cumulative MACEs (12.0% versus 22.7%, P = 0.022) and TLR/TVR (10.0% versus 18.7%, P = 0.047) were reduced in MSS group as compared to COS group, there was no difference in cardiac death, TVMI and ST between the groups. Compared to conventional overlapped stenting, modified single stenting for TCALs is associated with similar angiographic success, fewer one-year cumulative MACEs and less treatment cost.

Tau accumulation triggers STAT1-dependent memory deficits by suppressing NMDA receptor expression.

Intracellular tau accumulation forming neurofibrillary tangles is hallmark pathology of Alzheimer's disease (AD), but how tau accumulation induces synapse impairment is elusive. By overexpressing human full-length wild-type tau (termed hTau) to mimic tau abnormality as seen in the brain of sporadic AD patients, we find that hTau accumulation activates JAK2 to phosphorylate STAT1 (signal transducer and activator of transcription 1) at Tyr701 leading to STAT1 dimerization, nuclear translocation, and its activation. STAT1 activation suppresses expression of N-methyl-D-aspartate receptors (NMDARs) through direct binding to the specific GAS element of GluN1, GluN2A, and GluN2B promoters, while knockdown of STAT1 by AAV-Cre in STAT1flox/flox mice or expressing dominant negative Y701F-STAT1 efficiently rescues hTau-induced suppression of NMDAR expression with amelioration of synaptic functions and memory performance. These findings indicate that hTau accumulation impairs synaptic plasticity through JAK2/STAT1-induced suppression of NMDAR expression, revealing a novel mechanism for hTau-associated synapse and memory deficits.

Predictive Value of Peripheral Blood Neutrophil-To-Lymphocyte Ratio and Platelet-To-Lymphocyte Ratio on Patient Survival with Peritoneal Dialysis.

BACKGROUND: This study is to explore the predictive value of peripheral blood neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) on the prognosis of patients with peritoneal dialysis (PD). METHODS: A total of 378 patients who underwent PD from July 2004 to November 2019 were selected as the research subjects. According to whether death occurred during the follow-up period, they were divided into death group (86 cases) and survival group (292 cases). The differences in clinical indicators between the two groups were compared, and the multivariate Cox regression model and receiver operating characteristic curve (ROC) were used to analyze and summarize the factors affecting the prognosis of PD patients. RESULTS: Compared with the survival group, there were significant differences in age, lymphocytes, NLR, PLR, and combined cerebrovascular disease between the death group and the survival group (p < 0.05). Multivariate Cox regression analysis showed that advanced age (HR = 1.055, 95% CI: 1.038 - 1.072), increased NLR (HR = 1.136, 95% CI: 1.067 - 1.210), and increased PLR (HR = 1.184, 95% CI: 1.018 - 3.026) were risk factors for all-cause death in PD patients. The results showed that the area under the ROC curve (AUC) of NLR and PLR for predicting all-cause death of PD patients were 0.698 and 0.659, respectively, the sensitivity was 69.77%, and the specificity was 66.78% and 58.56%, respectively. The optimal critical values were NLR ≥ 3.71 and PLR ≥ 149.28. Taking the best cutoff value of the ROC curve as the threshold, it showed that the cumulative survival rate of patients with NLR ≥ 3.71 was significantly lower than that of patients with NLR < 3.71 (Log rank 2 = 37.551, p = 0.000). It also showed that the cumulative survival rate of patients with PLR ≥ 149.28 was lower than that of patients with PLR < 149.28 (Log rank 2 =23.686, p = 0.000). CONCLUSIONS: NLR and PLR have a good predictive effect on the prognosis of PD patients.

BACE1 SUMOylation increases its stability and escalates the protease activity in Alzheimer's disease.

Amyloid beta (Aß) is a major pathological marker in Alzheimer's disease (AD), which is principally regulated by the rate-limiting ß-secretase (i.e., BACE1) cleavage of amyloid precursor protein (APP). However, how BACE1 activity is posttranslationally regulated remains incompletely understood. Here, we show that BACE1 is predominantly SUMOylated at K501 residue, which escalates its protease activity and stability and subsequently increases Aß production, leading to cognitive defect seen in the AD mouse model. Compared with a non-SUMOylated K501R mutant, injection of wild-type BACE1 significantly increases Aß production and triggers cognitive dysfunction. Furthermore, overexpression of wild-type BACE1, but not non-SUMOylated K501R mutant, facilitates senile plaque formation and aggravates the cognitive deficit seen in the APP/PS1 AD mouse model. Together, our data strongly suggest that K501 SUMOylation on BACE1 plays a critical role in mediating its stability and enzymatic activity.

Effect of transient scrotal hyperthermia on human sperm: an iTRAQ-based proteomic analysis.

BACKGROUND: Through this prospective study, we aimed to explore the change of molecular modification after the transient scrotal hyperthermia on human sperm. METHODS: Ten healthy subjects selected with strict screening criteria underwent testicular warming in a 43 °C water bath for 30 min a day for 10 consecutive days. Semen samples were collected 2 weeks before the first heat treatment and 6 weeks after the first heat treatment. Proteins from the samples were labeled with isobaric tags for relative and absolute quantitation and analyzed by two-dimensional liquid chromatography-tandem mass spectrometry. RESULTS: In contrast to the control, of the 3446 proteins identified, 61 proteins were deregulated: 28 were up-regulated and 33 were down-regulated. Approximately 95% of the differentially expressed proteins were found to participate in spermatogenesis, fertilization, or other aspects of reproduction. In particular, the expression of sperm motility and energy metabolism-related proteins AKAP4, SPESP1, ODF1, ODF2, GAPDHS, and ACTRT2, validated by western blotting of the proteins obtained from human and mouse samples, tended to be reduced under scrotal hyperthermia. CONCLUSIONS: The results indicated that the proteins AKAP4, ODF1, ODF2, GAPDHS, SPESP1, and ACTRT2, play an important role in the heat-induced reversible reduction in sperm concentration and motility and have the potential to be the biomarkers and clinical targets for scrotal heat treatment induced male infertility.

Perilipin2 inhibits diabetic nephropathy-induced podocyte apoptosis by activating the PPARγ signaling pathway.

Podocyte apoptosis plays a pivotal role in the pathogenesis of diabetic nephropathy (DN). The main purpose of this study was to investigate the effects of perilipin2 on high glucose (HG)-induced podocyte apoptosis and associated mechanisms. Differentially expressed genes (DEGs) in BTBR ob/ob mice vs. nondiabetic mice kidneys were obtained from GSE106841 dataset and picked out using the 'limma' package. The protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) and was visualized by Cytoscape. Perilipin2 was a hub gene using the cytoHubba plug-in from Cytoscape. Gene ontology (GO) analysis revealed that the 126 overlapping DEGs were mainly enriched in 'oxidation reduction' [biological process, (BP)], metal ion binding' [molecular function, (MF)] and 'extracellular region' [cellular component, (CC)]. KEGG pathway analysis revealed that perilipin2 was mainly involved in 'PPAR signaling pathway'. DN inhibited perilipin2 expression and PPARγ expression, as by both in vitro and in vivo studies. In vitro experiments demonstrated that perilipin2 inhibition could not only reduced PPARγ expression in podocytes, it could also promote the apoptosis, and inhibit the viability in HG treated podocytes using western blot, CCK8 and flow cytometry assays. Perilipin2 overexpression reversed the effects of HG on inhibiting podocalyxin, nephrin, precursor (pro)-caspase-3/-9 and PPARγ protein expression and increasing cleaved caspase-3/-9 protein expression. Furthermore, the functions of perilipin2 overexpression reversing HG-induced podocyte apoptosis were inhibited by PPARγ inhibitor. In conclusion, the functions of DN-induced podocyte apoptosis were inhibited by activation of the PPARγ signaling pathway caused by perilipin2 overexpression.

The effect of Yang Yan Qing E Wan on senescent phenotypes and the expression of ß-catenin and p16INK4a in human skin fibroblasts.

This aim of this study was to observe the effect of Yang Yan Qing E Wan (YYQEW) on senescent phenotypes and the expression of ß-catenin and p16INK4a in the hydrogen peroxide (H2O2)-induced premature senescence of normal human skin fibroblasts (NHSFs). Primary normal human skin fibroblasts were randomly divided into a normal group, a blank group, a model group, and a YYQEW group. The cells of the model group and the YYQEW group were exposed to 150 µmol/L H2O2 for 2 h. The morphological changes of the cells were analyzed by microscopy and by kits used to estimate the activities of the senescence-associated ß-galactosidase (SA-ß-gal), reactive oxygen species (ROS), and superoxide dismutase (SOD). The outcomes revealed that dyeing rate proportion of SA-ß-gal was 2.78% ± 0.22% in the normal group, 2.83% ± 0.29% in the blank group, 37.58% ± 2.56% in the model group, and 28.39% ± 0.93% in the YYQEW group. The number of SA-ß-gal positive cells was thus significantly higher in the model group than in the normal or blank group. There were also fewer SA-ß-gal positive cells in the YYQEW group compared with the model group. The expression of ROS and p16INK4a in the model group increased significantly compared with that in the normal or blank groups, while the expression of ROS and p16INK4a in the YYQEW group decreased significantly compared with that in the model group. The expression of SOD and ß-catenin in the model group decreased significantly compared with that in the normal or blank group, and the expression of SOD and ß-catenin in the YYQEW group increased significantly compared with that in the model group. Overall, it was found that YYQEW was able to delay the senescence of NHSFs induced by H2O2 treatment by alleviating oxidative stress and regulating a number of senescence-related molecules, such as ß-catenin and p16INK4a.

[Preparation of Rhus chinensis total phenolic acid pellets by extrusion-spheronisation method].

Extrusion-spheronisation method was used to prepare Rhus chinensis total phenolic acid pellets. The formula and preparation of R. chinensis total phenolic acid pellets were optimized. The formulas( drug loading capacity,diluent,wetting agent and anti-sticking agent) were determined by the single factor test with yield,appearance and performance as the indexes. The preparation was optimized by Box-Behnken design and response surface method,with the rate of extrusion,rate of spheronization and time of spheronization as the independent variables and the overall desirability value of yield,friability and roundness as the dependent variables. The optimal formula of pellets was as follows: drug loading capacity 28. 7%,MCC-lactose 9 ∶1,silicon dioxide as anti-sticking agent,and 60% ethanol as wetting agent. The optimal preparation was determined as follows: the rate of extrusion was 43 r·min-1,the rate of spheronization was 1 800 r·min-1,and the time of spheronization was 4 min. The absolute deviation between predicted value and estimated value under the conditions was less than 5. 0%,with a high degree of model fit. The preparation parameters obtained were accurate,reliable and reproducible. Under scanning electron microscopy( SEM),R. chinensis total phenolic acid pellets were uniform in diameter,round and smooth. The optimal formulation and process are stable and feasible for preparing R. chinensis total phenolic acid pellets.

[Determination of seven ingredients of different grades Alismatis Rhizoma by QAMS method].

The present study is to establish a quantitative analysis of multi-components by single marker(QAMS) for determining contents of seven compositions in Alismatis Rhizoma, alismoxide, alisol C 23-acetate, alisol A, alismol, alisol B, alisol B 23-acetate and 11-deoxy-alisol B. Six relative correction factors(RCFs) of alismoxide, alisol C 23-acetate, alisol A, alismol, alisol B and 11-deoxy-alisol B were established in the UPLC method with alisol B 23-acetate as the internal standard, which was to calculate the mass fraction of each. The mass fraction of seven effective constituents in Alismatis Rhizoma was calculated by the external standard method(ESM) at the same time. Compared with the content results determined by the ESM and QAMS, the feasibility and accuracy of QAMS method were verified. Within the linear range, the RCFs of alismoxide, alisol C 23-acetate, alisol A, alismol, alisol B, 11-deoxy-alisol B were 0.946, 4.183, 0.915, 1.039, 0.923 and 1.244, respectively, with good repeatability in different experimental conditions. There was no significant difference between the QAMS method and ESM method. Then, QAMS method was applied to determination of the different degree Alismatis Rhizoma from different areas. As a result, the concentrations of 7 components have differences in different areas, but no significant differences in different grades. The QAMS method is feasible and accurate for the determination of the seven chemical compositions, and which can be used for quality control of Alismatis Rhizoma.

Study on the cephalopelvic relationship with cephalic presentation in nulliparous full-term Chinese pregnant women by MRI with three-dimensional reconstruction.

PURPOSE: To analyze the relationship between fetal head size and maternal pelvis size using magnetic resonance imaging (MRI) with a 3-D reconstruction technique. METHODS: A total of 301 nulliparous full-term Chinese pregnant women with cephalic presentation were enrolled and received MRI examinations before labor onset. Data were collected and imported into Mimics software to reconstruct the maternal pelvis and fetus. RESULTS: Of 301 pregnant women, 212 underwent vaginal delivery and 32 received cesarean section. The body mass index (BMI) was significantly different between the vaginal delivery group and the suspected cephalopelvic disproportion (CPD) group; the larger the BMI, the higher was the risk of CPD. The transverse diameter of the pelvic inlet and the posterior sagittal diameter of the midpelvis were significantly larger in the vaginal delivery group, compared with the suspected CPD group. Fetal weight > 3.5 kg could be used as a diagnostic indicator for CPD. CONCLUSIONS: BMI is a risk factor for CPD, and fetal weight < 3.5 kg is an important diagnostic indicator for natural delivery in Chinese pregnant women.

[Quality evaluation of Gualou Guizhi decoction based on chemical compositions and biological effects].

The paper was aimed to establish a quality evaluation model for Gualou Guizhi decoction based on the chemical compositions and biological effects. Ultra high performance liquid chromatograph-mass spectrometer was used to analyze and determine 24 kinds of chemical compositions in Gualou Guizhi decoction, and then, biological activity effect was quantitatively assessed in a zebrafish neuronal injury model which was induced by mycophenolate mofetil (MMF). As a result, the established method for quality evaluation of Gualou Guizhi decoction based on the chemical compositions and biological effects is feasible, stable and reliable, which can provide reference for quality control of compound Chinese medicines.

N,N-dimethylsphingosine attenuates myocardial ischemia-reperfusion injury by recruiting regulatory T cells through PI3K/Akt pathway in mice.

N,N-dimethylsphingosine (DMS) has been documented to be in vitro protective against myocardial ischemia-reperfusion injury (IRI) and can recruit CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), which may participate in the cardioprotection. We hypothesized that when in vivo applied after a myocardial ischemia, DMS may be cardioprotective by recruiting Tregs. Myocardial IRI was induced in C57BL/6 mice by occluding the left main coronary arteries followed by relaxation, and DMS (0.43 mg/kg) was intravenously injected 5 min after the onset of ischemia. We found that in wild-type (WT) mice, compared with the ischemia-reperfusion group, DMS reduced the infarct size (47.1 ± 8.9 vs. 33.1 ± 3.4 %, p < 0.01), and neutrophil infiltration at 24 h reperfusion (R) evaluated by TTC and immunohistochemical staining, respectively, and increased the aggregation of Tregs [(6 ± 1)/mm(2) vs. (30 ± 4)/mm(2), p < 0.01], peaking at 1 h R by immunofluorescence staining, with reduced gene expression of inflammatory factors at 4 h R in the reperfused myocardium by real-time PCR. This protection was abolished by phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor or Tregs-depleting antibody. Relative to WT mice, the cardioprotection conferred by T cell- and B cell- deficient Rag2 knockout (KO) mice was not strengthened by DMS or by DMS and the adoptive transfer of Tregs from WT mice, but was abolished by DMS and WT non-Tregs and was recaptured by the cotransfer with WT Tregs but not with Akt1(+/-) mice-derived Tregs. In conclusion, applied at an early stage of ischemia, DMS may be in vivo protective against myocardial IRI by recruiting Tregs via PI3K/Akt pathway.

The impact of rheumatoid arthritis on work capacity in Chinese patients: a cross-sectional study.

OBJECTIVE: To evaluate the impact of RA on work capacity and identify factors related to work capacity impairment in patients with RA. METHODS: A cross-sectional multicentre study was performed in 21 tertiary care hospitals across China. A consecutive sample of 846 patients with RA was recruited, of which 589 patients of working age at disease onset constituted the study population. Information on the socio-demographic, clinical, working and financial conditions of the patients was collected. Logistic regression analyses were used to identify factors associated with work capacity impairment. RESULTS: The rate of work capacity impairment was 48.0% in RA patients with a mean disease duration of 60 months (interquartile range 14-134 months), including 11.7% leaving the labour force early, 33.6% working reduced hours and 2.7% changing job. Multivariable logistic regression analysis showed that reduced working hours was significantly related to current smoking [odds ratio (OR) 2.07 (95% CI 1.08, 3.97)], no insurance [OR 1.94 (95% CI 1.20, 3.12)], in manual labour [OR 2.66 (95% CI 1.68, 4.20)] and higher HAQ score [OR 2.22 (95% CI 1.36, 3.60)]. There was an association of current smoking [OR 3.75 (95% CI 1.54, 9.15)], in manual labour [OR 2.33 (95% CI 1.17, 4.64)], longer disease duration [OR 1.01 (95% CI 1.00, 1.01)] and lower BMI [OR 0.90 (95% CI 0.82, 0.99)] with leaving the labour force early. CONCLUSION: There is a substantial impact of RA on the work capacity of patients in China. Social-demographic, disease- and work-related factors are all associated with work capacity impairment.

Targeted deletion of regulatory T cells attenuates the protective effects of myocardial ischemic preconditioning in rats.

BACKGROUND: Myocardial ischemia-reperfusion injury (IRI) is associated with activation of the innate immune system and the resultant inflammatory response. Myocardial ischemic preconditioning (IPC) is the most powerful endogenous protective mechanism against myocardial IRI, probably via the role of anti-inflammation. Regulatory T cells (Tregs), which are characterized by the expression of the forkhead/winged-helix transcription factor FoxP3, play an important role in the negative modulation of immune responses. We tested the hypothesis that Tregs may contribute to the protective effect of myocardial IPC through anti-inflammatory mechanisms. METHODS AND RESULTS: The left anterior descending coronary arteries of rats were occluded for a 30-min ischemia, followed by a 48-h reperfusion. Myocardial IPC was induced by 4 cycles of 5-min ischemia and 5-min reperfusion. Ischemia was achieved by ligation of the left anterior descending coronary artery (LAD), and reperfusion was initiated by releasing the ligature. Rats were injected with a Treg cell-depleting antibody or normal rat immunoglobulin (IgG), after IPC. The accumulation of Tregs was observed at indexed time points following IPC. The protein expression of FoxP3 significantly increased in the myocardium after IPC, and peaked at day-2. Treatment of preconditioned rats with the Treg cell-depleting antibody demonstrated less protein expression of FoxP3 (p < 0.001), more infiltration of inflammatory cells in the myocardium (p < 0.01), and larger myocardial infarct size (p < 0.001), compared with the IgG injection group. CONCLUSION: Cardioprotection by IPC is associated with Tregs.