LncRNA lnc-SPRR2G-2 contributes to keratinocyte hyperproliferation and inflammation in psoriasis by activating the STAT3 pathway and downregulating KHSRP.

Psoriasis is a chronic inflammatory disease characterized by increased keratinocyte proliferation and local inflammation. Long noncoding RNAs (lncRNAs) play important regulatory roles in many immune-mediated diseases, including psoriasis. In this study, we aimed to investigate the role and mechanism of lnc-SPRR2G-2 (SPRR2G) in M5-treated psoriatic keratinocytes. Fluorescence in situ hybridization and quantitative real-time polymerase chain reaction (qRT-PCR) showed that lnc-SPRR2G-2 was significantly upregulated in psoriasis tissues and psoriatic keratinocytes. In psoriatic keratinocytes, functional and molecular experiment analyses demonstrated that SPRR2G regulated proliferation, cell cycle and apoptosis, and induced the expression of S100 calcium binding protein A7 (S100A7), interleukin (IL)-1ß, IL-8 and C-X-C motif chemokine ligand 10 (CXCL10). The function of SPRR2G in psoriasis is related to the STAT3 signaling pathway and can be inhibited by a STAT3 inhibitor. Moreover, KH-type splicing regulatory protein (KHSRP) was proved to be regulated by lnc-SPRR2G-2 and to control the mRNA decay of psoriasis-related cytokines (p < 0.05). In summary, we reported the functions of lnc-SPRR2G-2 and KHSRP in psoriasis. Our findings provide new insights for the further exploration of the pathogenesis and treatment of psoriasis.

Transcriptional patterns of human retinal pigment epithelial cells under protracted high glucose.

BACKGROUND: The retinal pigment epithelium (RPE) is essential for retinal homeostasis. Comprehensively exploring the transcriptional patterns of diabetic human RPE promotes the understanding of diabetic retinopathy (DR). METHODS AND RESULTS: A total of 4125 differentially expressed genes (DEGs) were screened out from the human primary RPE cells subjected to prolonged high glucose (HG). The subsequent bioinformatics analysis is divided into 3 steps. In Step 1, 21 genes were revealed by intersecting the enriched genes from the KEGG, WIKI, and Reactome databases. In Step 2, WGCNA was applied and intersected with the DEGs. Further intersection based on the enrichments with the GO biological processes, GO cellular components, and GO molecular functions databases screened out 12 candidate genes. In Step 3, 13 genes were found to be simultaneously up-regulated in the DEGs and a GEO dataset involving human diabetic retinal tissues. VEGFA and ERN1 were the 2 starred genes finally screened out by overlapping the 3 Steps. CONCLUSION: In this study, multiple genes were identified as crucial in the pathological process of RPE under protracted HG, providing potential candidates for future researches on DR. The current study highlights the importance of RPE in DR pathogenesis.

Peripapillary hyperreflective ovoid mass-like structures with cystoid macular edema: a case report.

BACKGROUND: Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are newly characterized lesions wedged around the optic discs, which used to be misdiagnosed. Better understanding and identifying PHOMS are important for monitoring the condition of optic nerve. CASE PRESENTATION: A young female presented to the ophthalmic clinic with blurred vision of both eyes. Protrusions resembling "C-shaped donut" were found circling the optic discs bilaterally. These lesions were homogenous hyperreflective on OCT, while they were also hypoautofluorescent and hypoechogenic. Meanwhile, cystoid macular edema (CME) was also identified in both eyes. The patient was then diagnosed as PHOMS with CME. A short-term glucocorticoids therapy was prescribed systemically. The logMAR best-corrected visual acuity (BCVA) of both eyes reached 0.0 in 4 months with recovery of CME, while the PHOMS remained. CONCLUSIONS: There is currently no report on PHOMS with CME. More attentions should be paid to PHOMS, for they are potential biomarkers for axoplasmic stasis involved in different diseases of the optic nerve.

Skeleton-Based Fall Detection with Multiple Inertial Sensors Using Spatial-Temporal Graph Convolutional Networks.

The application of wearable devices for fall detection has been the focus of much research over the past few years. One of the most common problems in established fall detection systems is the large number of false positives in the recognition schemes. In this paper, to make full use of the dependence between human joints and improve the accuracy and reliability of fall detection, a fall-recognition method based on the skeleton and spatial-temporal graph convolutional networks (ST-GCN) was proposed, using the human motion data of body joints acquired by inertial measurement units (IMUs). Firstly, the motion data of five inertial sensors were extracted from the UP-Fall dataset and a human skeleton model for fall detection was established through the natural connection relationship of body joints; after that, the ST-GCN-based fall-detection model was established to extract the motion features of human falls and the activities of daily living (ADLs) at the spatial and temporal scales for fall detection; then, the influence of two hyperparameters and window size on the algorithm performance was discussed; finally, the recognition results of ST-GCN were also compared with those of MLP, CNN, RNN, LSTM, TCN, TST, and MiniRocket. The experimental results showed that the ST-GCN fall-detection model outperformed the other seven algorithms in terms of accuracy, precision, recall, and F1-score. This study provides a new method for IMU-based fall detection, which has the reference significance for improving the accuracy and robustness of fall detection.

Par3 regulates the asymmetric division of basal stem cells in psoriasis via the Par3/mInsc/LGN signaling axis.

OBJECTIVE: This research aimed to investigate the mechanism in psoriasis with the involvement of Par3-containing exosomes from macrophages by regulating the asymmetric division of basal stem cells. METHODS: BrdU labeling and double immunofluorescence assays were conducted to detect the proportion of asymmetric division in psoriasis mice. Western blot assay was conducted to examine the expression of Par3/mInsc/LGN signaling pathway-related proteins in psoriasis mice. Next, the asymmetric division of keratinocytes in normal mice treated with macrophages and their secreted exosomes were determined, together with the related protein detection. After establishing a macrophage-specific Par3 knockout mouse model, the asymmetric division of isolated keratinocytes and the related proteins were measured. An epidermal-specific mInsc, LGN, or NuMA knockout mouse model was induced, followed by the determination of the asymmetric division of isolated keratinocytes. RESULTS: The asymmetric division of basal stem cells was increased, and the expression of Par3/mInsc/LGN signaling pathway-related proteins was elevated in psoriasis. Par3-containing macrophage-derived exosomes enhanced asymmetric division of basal stem cells and expression of Par3/mInsc/LGN signaling pathway-related proteins in mice. However, mice with Par3 loss presented opposite trends. There was a decreased asymmetric division of basal stem cells in epidermal-specific mInsc, LGN, and NUMA knockout mice. CONCLUSION: Our study suggests that macrophage-derived exosomes-shuttled Par3 are absorbed by the basal stem cells and regulate the asymmetric division of cells to produce a large number of transit-amplifying cells, thus causing psoriasis-related symptoms in conjunction with various other factors.

CircEIF5 contributes to hyperproliferation and inflammation of keratinocytes in psoriasis via p-NFκB and p-STAT3 signalling pathway.

Psoriasis is a chronic, immune-mediated skin disease accompanied by hyperproliferation and inflammation of keratinocytes. Circular RNAs (circRNAs) as new players regulating the development of psoriasis have been reported in recent years. However, its mechanism has not yet been fully revealed. In this study, we identified that hsa_circ_0033469 (circEIF5) was highly expressed in psoriasis tissues compared with the normal skin. We investigated the functional roles of circEIF5 in proliferation and inflammatory of HaCat cells under M5-stimulated inflammatory condition. By using a approach of knockdown and overexpression of circEIF5, we showed that circEIF5 could promote proliferation by facilitating the G1/S transition and increase secretion of chemokines in HaCat cells. These moderating effects of circEIF5 were associated with the activating of the NF-κB and STAT3 signalling pathways. Moreover, NF-κB and STAT3 inhibition abrogated circEIF5-induced promotion of cell proliferation and chemokine secretion. These results indicated that through NF-κB and STAT3 signalling pathways, circEIF5 regulated the proliferation and chemokine secretion of HaCat cells and contributed to the pathogenesis of psoriasis, which might become a potent target for psoriasis treatment.

Immunoadsorption Improves Remission Rates of Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Severe Kidney Involvement.

INTRODUCTION: The role of plasma exchange in treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with severe kidney involvement is controversial. It is urgent to find effective treatments to improve prognosis of AAV patients. In this retrospective study, the outcomes of immunoadsorption (IA) onto protein A in AAV patients with severe kidney involvement were evaluated. METHODS: Clinical data of 60 patients with AAV and severe kidney involvement were analyzed. Patients received cyclophosphamide or rituximab for remission induction, among which 16 were additionally treated with IA. Remission, end-stage kidney disease (ESKD), death, and relapse were compared. RESULTS: Of 60 patients, 56 patients (93.3%) were positive for myeloperoxidase (MPO)-ANCA. At diagnosis, the estimated glomerular filtration rate and Birmingham Vasculitis Activity Score (BVAS) was 13.0 (7.7, 18.7) mL/min/1.73 m2 and 11.1 ± 3.4, respectively. After 3-17 days (mean 10.4 days) of induction treatment, the disease activity decreased more obviously in the IA group (p = 0.022) than the control group. IA showed superior over standard regimen in clearance of MPO-ANCA within 3-31 days (median 11 days) after treatment (78.4% vs. 9.3%, p = 0.005). After a median follow-up of 20.2 months, remission was achieved more quickly (p = 0.035) and higher (hazard ratio (HR) = 2.3, 95% confidence interval (CI): 1.1∼7.2, p = 0.033) in the IA group than the control group. IA therapy showed an advantage in reducing death (HR = 0.2, 95% CI: 0.1∼0.9, p = 0.032). There was no difference in developing into ESKD in both groups (HR = 0.7, 95% CI: 0.3∼2.0, p = 0.504). Multivariate Cox regression analysis indicated that early-stage remission was an independent predictor for ESKD (HR = 0.03, 95% CI: 0.003∼0.25, p = 0.001) and death (HR = 0.07, 95% CI: 0.01∼0.51, p = 0.009). CONCLUSION: IA treatment induces quicker and higher remission and lower mortality in AAV patients with severe kidney involvement. The early remission independently predicts the outcomes for these patients.

Effects of sleep habits on acute myocardial infarction risk and severity of coronary artery disease in Chinese population.

BACKGROUND: Growing evidence indicates that poor sleep harms health. Early to bed and early to rise is considered as a healthy lifestyle in Chinese population. The current study aimed to examine the effects of sleep habits on acute myocardial infarction (AMI) risk and severity of coronary artery disease (CAD) in Chinese population from two centers. METHODS: A total of 873 patients including 314 AMI cases and 559 controls were recruited from the inpatient cardiology department of the Affiliated Jiangning Hospital and the First Affiliated Hospital of Nanjing Medical University. 559 controls included 395 CAD cases and 164 non-CAD cases. We used a 17-item sleep factors questionnaire (SFQ) to evaluate sleep habits comprehensively by face-to-face interview. The severity of CAD was assessed by Gensini score in AMI and CAD groups. The effects of sleep factors on AMI risk and Gensini score were examined by unconditional logistic regression. RESULTS: After mutually adjustment for other sleep factors and demographic characteristics, the timing of sleep (24:00 and after) and morning waking (after 7:00) and sleep duration (< 6 h) were associated with increased risk of AMI (OR = 4.005, P < 0.001, OR = 2.544, P = 0.011 and OR = 2.968, P < 0.001, respectively). Lower level of light exposure at night was correlated with reduced risk of AMI (OR = 0.243, P = 0.009). In subgroup analysis by age, both late sleep timing and short sleep duration were associated with increased risk of AMI regardless of age. In subjects with age ≤ 65 years, daytime napping was related to reduced risk of AMI (OR = 0.645, P = 0.046). In subjects with age > 65 years, the frequency of night-time waking (3 times) was associated with increased risk of AMI (OR = 3.467, P = 0.035). Short sleep duration was correlated with increased risk of high Gensini score (OR = 2.374, P < 0.001). CONCLUSION: Sleep insufficiency is an important risk factor both for AMI risk and CAD severity. Late sleeping is also associated with increased risk of AMI. In young and middle-aged people, regular naps may have a protective effect.

The lncRNA H19/miR-766-3p/S1PR3 Axis Contributes to the Hyperproliferation of Keratinocytes and Skin Inflammation in Psoriasis via the AKT/mTOR Pathway.

BACKGROUND: The pathogenesis of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are well studied in psoriasis. However, little is known about how specific lncRNAs and miRNAs affect the mechanism of psoriasis development and which pathways are involved. OBJECTIVES: To explore the role of the lncRNA H19/miR-766-3p/S1PR3 axis in psoriasis. METHODS: miRNA and lncRNA microarrays were performed using IL-22-induced HaCaT cells and psoriatic lesions, respectively. Fluorescence in situ hybridization and quantitative reverse-transcriptase polymerase chain reaction were used to detect the expression of miR-766-3p and lncRNA H19. Luciferase reporter assays were used to identify miR-766-3p/lncRNA H19 and miR-766-3p/S1PR3 combinations. CCK-8 and ELISA were performed to evaluate the proliferation of keratinocytes and the secretion of pro-inflammatory cytokines. Western blot analysis was used to detect the expression of S1PR3 and its downstream effector proteins. RESULTS: MiR-766-3p was upregulated in both HaCaT cells treated with the psoriasis-related cytokine pool (IL-17A, IL-22, IL-1 alpha, oncostatin M, and TNF-alpha) and tissues. Overexpression of miR-766-3p promoted keratinocyte proliferation and IL-17A and IL-22 secretion. LncRNA H19 and S1PR3 were demonstrably combined with miR-766-3p by luciferase reporter assay. lncRNA H19 repressed proliferation and inflammation, which were reduced by the miR-766-3p. AKT/mTOR pathway effected proliferation and inflammation by the lncRNA H19/miR-766-3p/S1PR3 axis. CONCLUSIONS: We established that downregulation of lncRNA H19 promoted the proliferation of keratinocytes and skin inflammation by up-regulating miR-766-3p expression levels and inhibiting activation of S1PR3 through the AKT/mTOR pathway in psoriasis.

Damage Orientation and Depth Effect on the Guided Wave Propagation Behavior in 30CrMo Steel Curved Plates.

s: In this paper, the guided wave propagation behavior in damaged 30CrMo steel curved plates was investigated experimentally and numerically. The effects of the notch orientation, depth in the curved plate, as well as its radius, on the wave propagation characteristics were mainly analyzed by the amplitude distribution curves and the directivity diagrams of A0/S0 (zero-th order of the symmetric/antisymmetric Lamb wave) modes. An ellipse-based algorithm was compiled to locate the notches in the curved plates. Results show that the normalized S0 wave amplitude in the circumferential orientation was the largest, and it increases as notch depth increases in the axial orientation. The A0 wave amplitude in axial orientation was the largest, while it decreases with the increasing of notch depth in the other orientations. The normalized A0 wave amplitude in axial orientation increases with the increasing of radius. With the increasing of radius, the other normalized A0/S0 amplitudes linearly decreased for the other paths. The ellipse-based algorithm has high notch localization accuracy, and the notch localization error increase from 0.005% to 1.47% with the notch depth decreasing from 5 mm to 1 mm in the curved plates. For the curved plates with different radius, the maximum notch localization error is 1.20%. These satisfactory results demonstrate the effectiveness of the developed algorithm in locating damages in the researched structure.

Up-regulated lncRNA-MSX2P1 promotes the growth of IL-22-stimulated keratinocytes by inhibiting miR-6731-5p and activating S100A7.

Competitive endogenous RNAs (ceRNAs) regulate RNA transcripts by competing for shared miRNAs and play critical roles in disease development. Psoriasis is a long-lasting, recurring chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes. The keratinocyte response is triggered by the activation of inflammatory cytokines, like interleukin-22 (IL-22). We used lncRNA array analysis to detect differentially expressed lncRNAs in skin (HaCaT) cells treated with or without IL-22. We used hematoxylin and eosin (H&E) staining to determine the pathological changes in skin cells and immunohistochemistry to evaluate the expression of S100A7. We used qRT-PCR and Western blotting to detect the expression levels of MSX2P1 and S100A7. We down-regulated the expression of MSX2P1 by infecting with lentiviral-vector shRNA. We measured cell proliferation, cell cycle status, and apoptosis by the CCK-8 assay, flow cytometry, and Annexin Ⅴ-FITC/PI staining, respectively. In addition, we used the luciferase reporter gene assay to determine the relationships between MSX2P1 or miR-6731-5p and S100A7, respectively. LncRNA array analysis revealed that 103 lncRNAs were up-regulated and 51 were down-regulated. Furthermore, qRT-PCR showed that the mRNAs levels of MSX2P1 was significantly altered in HaCaT cells treated with IL-22, compared with control cells; and MSX2P1 was mainly in the cytoplasm. Based on the IL-22-stimulated lncRNA-associated ceRNA network, we selected MSX2P1-miR-6731-5p-S100A7 for further study. H&E staining exhibited characteristic features specific to psoriatic lesions. Immunohistochemistry demonstrated significantly increased expression levels of S100A7 in psoriatic lesions, compared with normal skin tissue. We observed a positive correlation between lncRNA-MSX2P1 expression and S100A7 expression. In addition, miR-6731-5p suppressed proliferation, accelerated apoptosis in IL-22-stimulated keratinocytes, and decreased the expressions of S100A7, IL-12ß, IL-23, HLA-C, CCHCR1, TNF-α, and NF-κB proteins. Our data demonstrated that MSX2P1 facilitate the progression and growth of IL-22-stimulated keratinocytes by inhibiting miR-6731-5p and activating S100A7. We speculate that the biological network of MSX2P1-miR-6731-5p-S100A7 is a potential novel therapeutic target for the future treatment of psoriasis.

Circular RNA Expression Profile and Analysis of Their Potential Function in Psoriasis.

BACKGROUND/AIMS: Circular RNAs (circRNAs) are evolutionary conserved circular non-coding RNAs that play a role in several diseases by sequestering (sponging) microRNAs (miRNAs). However, their role in psoriasis remains unclear. In the present study, we investigated the expression of circRNAs and analyzed their potential functions in psoriasis. METHODS: The SBC human ceRNA array V1.0 was used to analyze circRNA expression in psoriatic lesions and normal healthy skin tissues. Functional analyses were performed using Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Putative miRNA response elements (MREs) were identified using miRNA target prediction software. Six upregulated circRNAs were verified by quantitative real-time reverse transcription polymerase chain reaction in psoriatic lesions and healthy skin tissues. RESULTS: A total of 4956 circRNAs (3016 upregulated and 1940 downregulated; fold change ≥2 and p< 0.05) were identified as differentially expressed in psoriasis. Furthermore, 4405 MREs were identified among the differentially expressed circRNAs. hsa_circ_0061012 was upregulated in psoriatic lesions compared with normal healthy skin tissues. The top five MREs of hsa_circ_0061012 were hsa-miR-7157-5p, hsa-miR-4769-3p, hsa-miR-6817-5p, hsa-miR-4310, and hsa-miR-6882-3p. GO analysis was carried out to investigate the biological functions enriched among the upregulated targets of five miRNAs in psoriasis. The GO analysis identified that most of top 30 of GO enrichment are related to psoriasis. CONCLUSION: hsa_circ_0061012 might be a candidate biomarker for psoriasis. The results provide a new perspective for a better understanding of ceRNA-mediated gene regulation in psoriasis, and provide a novel theoretical basis for further studies on the function of circRNA in psoriasis.

A study of the association of rs12040273 with susceptibility and severity of coronary artery disease in a Chinese Han population.

BACKGROUND: The single nucleotide polymorphism (SNP) rs12040273, a variant of UDP-N-acetylgalactosamine, polypeptide GalNAc-transferase 2, has recently been reported to be significantly associated with development of carotid artery intima-media thickness (IMT) in a Chinese population based on a genome-wide association study. Because IMT is a potent marker of coronary artery disease (CAD), the aim of this study was to evaluate the relation of rs12040273 to susceptibility and severity of CAD in a Chinese Han population. METHODS: We performed a hospital-based case-control study. Three hundred and thirty-one individuals (199 CAD patients and 112 non-CAD controls) undergoing coronary angiography were consecutively enrolled in the study. The Gensini score results were used to assess the severity of CAD. The method of polymerase chain reaction-ligase detection reaction (PCR-LDR) was used to distinguish different genotypes at rs12040273. RESULTS: The distribution of genotypes at rs12040273 was comparable between CAD patients and non-CAD controls (P > 0.05). The frequencies of the genotypes were also not significantly associated with the risk of CAD and its severity assessed by the Gensini score method, with the OR of 1.38 (95% CI = 0.80-2.40, P = 0.24) and 1.14 (95% CI = 0.69-1.86, P = 0.60) respectively. However, stratified analysis showed that the serum HDL-C levels of subjects with the CC genotype were significantly higher than those with CT/TT genotypes in non-CAD controls (P = 0.002). CONCLUSION: Our results suggest that the rs12040273 variants might not be associated with the susceptibility of CAD or its severity in a Chinese Han population. Moreover, the CC genotype could be associated with elevated serum HDL-C levels.

Predictive value of plasma copeptin level for the risk and mortality of heart failure: a meta-analysis.

Epidemiologic studies are inconsistent regarding the association between plasma copeptin level and heart failure (HF). The aim of this study was to perform a meta-analysis to determine whether high level of copeptin is correlated with incidence of HF and mortality in patients with HF. We searched PUBMED and EMBASE databases for studies conducted from 1966 through May 2016 to identify studies reporting hazard ratio (HR) estimates with 95% confidence intervals (CIs) for the association between plasma copeptin level and HF. A random-effects model was used to combine study-specific risk estimates. A total of 13 studies were included in the meta-analysis, with five studies on the incidence of HF and eight studies on the mortality of patients with HF. For incidence of HF, the summary HR indicated a borderline positive association of high plasma copeptin level with HF risk (HR, 1.60; 95% CI, 0.90-2.85). Furthermore, an increase of 1 standard deviation in log copeptin level was associated with a 17% increase in the risk of incident HF (HR, 1.17; 95% CI, 1.02-1.33). For all-cause mortality of patients with HF, we also found a significant association between elevated plasma copeptin level and increased mortality of HF (HR, 1.76; 95% CI, 1.33-2.33). Our dose-response analysis indicated that an increment in copeptin level of 1 pmol/l was associated with a 3% increase in all-cause mortality (HR, 1.03; 95% CI, 1.01-1.05). In conclusion, our results suggest that elevated plasma copeptin level is associated with an increased risk of HF and all-cause mortality in patients with HF.

Association in a Chinese population of a genetic variation in the early B-cell factor 1 gene with coronary artery disease.

BACKGROUND: Early B-cell factor 1 (EBF1) is a transcription factor expressed primarily during early B cell development. Previous studies have shown EBF1 regulates blood glucose and lipid metabolism in mice with diabetes and central adiposity. Recently, a genetic variation (rs36071027) located in an EBF1 gene intron was associated with carotid artery intima-media thickness. However, whether this polymorphism is actually linked with coronary artery disease (CAD) and its severity remains unclear. METHODS: This study includes 293 CAD cases and 262 controls without CAD. All participants were devided into two groups based on their coronary angiography results. A polymerase chain reaction-ligase detection reaction was used to identify genotypes at rs36071027, and CAD patients were further divided into subgroups with one-, two-, or three-vessel stenosis reflective of CAD severity. RESULTS: The frequency of the rs36071027 TT genotype was significantly higher in CAD cases versus controls (4.8% vs. 1.5%, 95% CI: 1.13-10.81 P = 0.029). Subjects with a variant genotype T allele had an increased risk of CAD compared to C allele carriers (additive model: 95% CI: 1.13-2.23, P = 0.008). After adjustment for cardiovascular risk factors, analysis of the additive and dominant models involving rs36071027 also revealed that T allele carriers had a significantly higher risk for CAD than C allele carriers (additive model: OR 1.56, 95% CI 1.10-2.22, P = 0.013; dominant model: OR 1.60, 95% CI 1.07-2.41, P = 0.023). Furthermore, both diabetes and the CT + TT rs36071027 genotype were significantly associated with three-vessel stenosis. CONCLUSION: Our results in a Chinese population suggest that the TT genotype and T alleles in rs36071027 in the EBF1 gene are associated with an increased risk of CAD and its severity.

Inhibition of EMMPRIN and MMP-9 Expression by Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor in PMA-Induced Macrophages.

BACKGROUND/AIMS: It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer) and MMPs (matrix metalloproteinases) by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG) has a variety of pharmacological properties and exerts cardiovascular protective effects. Recently, the 67-kD laminin receptor (67LR) has been identified as a cell surface receptor of EGCG. The aim of the present study was to evaluate the effects of EGCG on the expression of EMMPRIN and MMP-9 in PMA-induced macrophages, and the potential mechanisms underlying its effects. METHODS: Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Protein expression and MMP-9 activity were assayed by Western blot and Gelatin zymography, respectively. Real-time PCR was used to examine EMMPRIN and MMP-9 mRNA expression. RESULTS: We showed that EGCG (10-50µmol/L) significantly inhibited the expression of EMMPRIN and MMP-9 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) in PMA-induced macrophages. Downregulation of EMMPRIN by gene silencing hindered PMA-induced MMP-9 secretion and expression, indicating an important role of EMMPRIN in the inhibition of MMP-9 by EGCG. Moreover, 67LR was involved in EGCG-mediated suppression of EMMPRIN and MMP-9 expression. Anti-67LR antibody treatment led to abrogation of the inhibitory action of EGCG on the expression of EMMPRIN and MMP-9 and activation of ERK1/2, p38, and JNK. CONCLUSION: Our results indicate that EGCG restrains EMMPRIN and MMP-9 expression via 67LR in PMA-induced macrophages, which also suggests that EGCG may be a possible therapeutic agent for stabilizing atherosclerotic plaque.

Association of rs10811656 on 9P21.3 with the risk of coronary artery disease in a Chinese population.

BACKGROUND: Genome-wide association studies have reported that the 9p21.3 locus confers risk for coronary artery disease (CAD). However, it is not known whether rs10811656 is linked with CAD in a Chinese population. Thus, the purpose of this study was to investigate the potential association between rs10811656 and the risk of CAD in a Chinese population. METHODS: We conducted a hospital-based, case-control study with 251 CAD patients and 304 controls to examine the potential association of rs10811656 with CAD. RESULTS: The frequencies of the TT genotypes in CAD cases were significantly different from those in controls (adjusted OR: 1.96, 95 % CI: 1.09-3.505, P = 0.024). Compared to controls, rs10811656 was significantly associated with the stable angina pectoris (adjusted OR: 1.42, 95 % CI: 1.06-1.90, P = 0.017), but not with acute coronary syndrome. There was also a highly significant association of rs10811656 with double-vessel and triple-vessel disease when patients were divided into subgroups based on the number of diseased vessels (adjusted OR: 1.68 and 1.60, 95 % CI: 1.14-2.44 and 1.10-2.33, P = 0.009 and 0.02, respectively). CONCLUSION: Our results suggest that the rs10811656 locus might be associated with CAD in a Chinese Han population.

Symptom clustering in chronic gastritis based on spectral clustering.

OBJECTIVE: Apply spectral clustering to analyze the patterns of symptoms in patients with chronic gastritis (CG). METHODS: Based on 919 CG subjects, we applied mutual information feature selection to choose the positively correlated symptoms with each pattern. Then, we used the Shi and Malik spectral clustering algorithm to select the top 20 correlated symptoms. RESULTS: We ascertained the results of six patterns. There were three categories for the pattern of accumulation of damp heat in the spleen-stomach (0.00332). There were six categories for the pattern of dampness obstructing the spleen-stomach (0.02466). There were two categories for the pattern of spleen-stomach Qi deficiency (0.013 89). There were three categories for the pattern of spleen-stomach deficiency cold (0.009 15). There were five categories for the pattern of liver-Qi stagnation (0.01910). There were four categories for the pattern of stagnant heat in the liver-stomach (0.00585). CONCLUSION: Most of the spectral clustering results of the symptoms of CG patterns were in accordance with clinical experience and Traditional Chinese Medicine theory. Most categories suggested the nature and/or location of the disease.

[Analysis of false-positive hyoid fractures: 12 forensic identification cases].

OBJECTIVE: To study the causes of false-positive hyoid fractures and forensic identification. METHODS: Twelve cases of false-positive hyoid fractures were collected and analyzed. RESULTS: Improper dissection technique (4 cases) and congenital separation (8 cases) were the main reasons for false-positive hyoid fractures. CONCLUSION: True fractures can be differentiated from false-positive hyoid fractures. False-positive hyoid fracture caused by improper dissection technique can be identified through examination of peripheral muscle, soft tissue hemorrhage, and the characteristics of fracture end.

[Correlation between age and general morphology of transverse section of cartilago costalis].

OBJECTIVE: To study the correlation between age and general morphology of transverse section of cartilago costalis and its forensic significance. METHODS: Eighty-six corpses' cartilago costalis from the routine postmortem examination were collected and the morphological features of their transverse section were observed. RESULTS: With the increased age, there were regular changes in the color, structure, and material of the general morphology of transverse section of cartilago costalis. But the changes were not affected by gender. CONCLUSION: The good correlation between general morphology of transverse section of cartilago costalis and age can be used to estimate age of the deceased rapidly.