[Correlation between dyslipidemia and rheumatoid arthritis associated interstitial lung disease].

OBJECTIVE: To study the correlation between dyslipidemia and rheumatoid arthritis associa-ted interstitial lung disease (RA-ILD) by retrospective analysis of the clinical data. METHODS: The clinical data of patients with rheumatoid arthritis (RA), who were hospitalized in the Department of Rheumatism and Immunology of Peking University Shenzhen Hospital from January 2015 to July 2020 and fulfilled the criteria of the 2010 Rheumatoid Arthritis Classification Criteria established by American College of Rheumatology/European League Against Rheumatism collaborative initiative, were collected and analyzed. RESULTS: There were 737 RA patients included, of whom 282(38.26%)were with interstitial lung disease (ILD). The median time from the onset of the first RA-related clinical symptoms to the onset of ILD was 13 years (95%CI 11.33-14.67). By multivariate Logistic regression analysis, we found that low-density lipoprotein cholesterol (LDL-C) was an independent risk factor for RA-ILD (OR 1.452, 95%CI 1.099-1.918, P=0.009), whereas high-density lipoprotein cholesterol (HDL-C) was a protective factor for RA-ILD (OR 0.056, 95%CI 0.025-0.125, P < 0.001). The RA patients with high LDL-C or low HDL-C had higher incidence of ILD than that of the RA patients with normal LDL-C or HDL-C(57.45% vs. 36.96%, P < 0.001; 47.33% vs. 33.81%, P < 0.001, respectively). The median time of ILD onset in the RA patients with low HDL-C was shorter than that of the RA patients with normal HDL-C [10.0(95%CI 9.33-10.67)years vs.17.0 (95%CI 14.58-19.42) years, P < 0.001]. HDL-C level was negatively correlated with disease activity. Among the RA-ILD patients, the patients with low HDL-C had higher percentage of usual interstitial pneumonia (UIP) then that of the patients with normal HDL-C (60.00% vs. 53.29%, P=0.002). The RA-ILD patients with high LDL-C had higher incidence rate of decrease in forced vital capacity (FVC) than that of the RA-ILD patients with normal LDL-C (50.00% vs. 21.52%, P=0.015). The RA-ILD patients with low HDL-C had higher incidence rate of decrease in FVC (26.92% vs. 16.18%, P=0.003) and carbon monoxide diffusion (80.76% vs. 50.00%, P=0.010) than that of RA-ILD patients with normal HDL-C. CONCLUSION: LDL-C was possibly a potential independent risk factor for RA-ILD. HDL-C was possibly a potential protective factor for RA-ILD. HDL-C level was negatively correlated with disease activity of RA. The median time of ILD onset in the RA patients with low HDL-C was significantly shorter than that of the RA patients with normal HDL-C.

[Clinical features of severe acute respiratory syndrome coronavirus 2 Omicron variant infection in children: an analysis of 201 cases]. / 201ä¾‹å„¿ç«¥æ–°åž‹å† çŠ¶ç— æ¯’Omicronå˜å¼‚æ ªæ„ŸæŸ“çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. METHODS: A retrospective analysis was performed on the medical data of 201 children with coronavirus disease 2019 (COVID-19) who were hospitalized and diagnosed with SARS-CoV-2 Omicron variant infection in Quanzhou First Hospital from March 14 to April 7, 2022. Among the 201 children, there were 34 children with asymptomatic infection and 167 with symptomatic infection. The two groups were compared in terms of clinical features, results of experimental examinations, and outcome. RESULTS: Of all the 201 children, 161 (80.1%) had a history of exposure to COVID-19 patients and 132 (65.7%) had a history of COVID-19 vaccination. Among the 167 children with symptomatic infections, 151 had mild COVID-19 and 16 had common COVID-19, with no severe infection or death. Among the 101 children who underwent chest CT examination, 16 had ground glass changes and 20 had nodular or linear opacities. The mean time to nucleic acid clearance was (14±4) days for the 201 children with Omicron variant infection, and the symptomatic infection group had a significantly longer time than the asymptomatic infection group [(15±4) days vs (11±4) days, P<0.05]. The group vaccinated with one or two doses of COVID-19 vaccine had a significantly higher positive rate of IgG than the group without vaccination (P<0.05). The proportions of children with increased blood lymphocyte count in the symptomatic infection group was significantly lower than that in the asymptomatic infection group (P<0.05). Compared with the asymptomatic infection group, the symptomatic infection group had significantly higher proportions of children with increased interleukin-6, increased fibrinogen, and increased D-dimer (P<0.05). CONCLUSIONS: Most of the children with Omicron variant infection have clinical symptoms, which are generally mild. The children with symptomatic infection are often accompanied by decreased or normal blood lymphocyte count and increased levels of interleukin-6, fibrinogen, and D-dimer, with a relatively long time to nucleic acid clearance. Some of them had ground glass changes on chest CT.

Effects of extracellular ATP on local and systemic responses of bean (Phaseolus vulgaris L) leaves to wounding.

Wounding increased the extracellular Adenosine 5'-triphosphate (eATP) level of kidney bean leaves. Treatment with wounding or exogenous ATP increased the hydrogen peroxide (H2O2) content, activities of catalase and polyphenol oxidase, and malondialdehyde content in both the treated and systemic leaves. Pre-treatment with ATP-degrading enzyme, apyrase, to the wounded leaves reduced the wound-induced local and systemic increases in H2O2 content, activities of catalase and polyphenol oxidase, and malondialdehyde content. Application of dimethylthiourea (DMTU) and diphenylene iodonium (DPI) to the wounded and ATP-treated leaves, respectively, reduced the wound- and ATP-induced local and systemic increases in H2O2 content, activities of catalase and polyphenol oxidase, and malondialdehyde content. Moreover, the wound- and ATP-induced systemic increases of these physiological parameters were suppressed when DMTU or DPI applied to leaf petiole of the wounded and ATP-treated leaves. These results suggest that eATP at wounded sites could mediate the wound-induced local and systemic responses by H2O2-dependent signal transduction.

[Characteristics of Organic Matter Composition and Oxidation Potential in Road Dust in Winter in Xi'an].

Roads are the main places where urban people are exposed to atmospheric particulate matter from outdoor activities, and certain oxidatively active substances contained in road particulate matter are important components that induce the generation of reactive oxygen species (ROS), which in turn endanger human health. Here, we explored the characteristics of organic matter composition in water-soluble (WSM) and methanol-soluble fractions (MSM) of road dust in Xi'an and its oxidation potential (OP). Additionally, we investigated the organic fractions and their distribution based on parallel factor analysis (PARAFAC) and analyzed the correlation between organic matter types and OP. The results showed that the water-insoluble fraction of road dust in Xi'an contained more chromophoric organic matter with an average total concentration of (4.71±1.27)×104 R.U., which was 12 times higher than that of WSM[(3.96±1.10)×103 R.U.], of which low-oxidizing humic-like substances (HULIS) were the main organic matter (34.8%-43.7% of the total organic matter). The results of cluster analysis showed that the important sources of organic matter in road dust in Xi'an were fuel combustion and industrial production. The mean value of dust oxidative toxicity was (0.34±0.08) pmol·(min·µg)-1, with the water-insoluble fraction providing 70% of the total oxidative toxicity of dust particles, which was 2.4 times higher than the water-soluble fraction. The main precursors of oxidative toxicity of dust particles were metal elements, and special types of organic substances were also one of the important oxidative toxicity precursors, among which chromophore organic matter was the main cause of OP production in the WSM fraction (r=0.35, P<0.01), and protein-like organic matter and highly oxidized HULIS in WSM may have been the main two types of organic substances for OP production. However, there was no significant correlation between organic matter concentration in MSM and water-insoluble OP (OPTotal-OPWSM) (r=-0.04, P>0.1), so the oxidative toxicity of the water-insoluble particulate matter fraction was mainly generated from non-organic matter.

[Expression of transforming growth factor beta 1 and conection tissue growth factor in ankylosing spondylitis].

OBJECTIVE: To investigate the expressions of transforming growth factor beta 1(TGF-ß1) /smad, connective tissue growth factor (CTGF), collagen I and collagen III in ankylosing spondylitis (AS). METHODS: Thirty patients with AS were included in the study. All the patients were performed with computed tomography-guided needle biopsy in sacroiiliac joint. Sera TGF-ß1 and CTGF were determined by enzyme-linked immunosorbent assay (ELISA). Immunohistologic studies were performed with the alkaline phosphatase-anti-alkaline phosphatase technique to assess the expressions of TGF-ß1, p-smad3, smad7, CTGF, collagen I and collagen III in sacroiiliac joint tissue samples. RESULTS: In the AS patients, neither serum TGF-ß1 level nor serum CTGF level was found significantly different from that of the controls [(6.7±2.1)mg/L vs.(5.4±5.8)mg/L, P<0.05, (0.83±0.46)µg/L vs.(1.07±0.79 )µg/L, P<0.05]. In contrast to the healthy controls, TGF-ß1 and CTGF were found upexpressed in cytoplasm of inflammatory cells in pannus and bone marrow in sacroiliac tissue samples of patients with AS [(104.5±66.2) /HP vs. (24.4±9.3) /HP, (57.94±42.40) /HP vs. (2.67±2.52) /HP]. Meantime, p-smad3 was found expressed in the nuclear, while smad7 was detected to be downexpressed. Additionally, collagen I and collagen III were found upexpressed in bone, cartilage and ligament tissue. CONCLUSION: TGF-ß1, CTGF, collagen I and collagen III were upexpressed in sarcoiliac joints of AS patients. TGF-ß1/CTGF may play an important role in articular cartilage fibrosis and ossification of AS by smad signal pathyway.

Evaluation of metabolic risk marker in obesity-related glomerulopathy.

OBJECTIVE: Insulin resistance is a common metabolic abnormality, which increases the risk of renal events in obesity. The present study is aimed to examine the relation between metabolic factors and obesity-related glomerulopathy (ORG), and then compare the risk markers of insulin resistance for clinical prediction. METHODS: A total of 112 cases with proven renal ORG and 135 age- and gender-matched lean controls were included. The degree of proteinuria, endogenous creatinine clearance rate, body mass index, amylin, fasting glucose, insulin, lipid and lipoprotein concentrations were measured during the steady state. RESULTS: The patients with ORG were clinically characterized by increased body mass index and proteinuria, with higher levels of amylin, homeostasis model assessment of insulin resistance (HOMA-IR), insulin, glucose, and lipid proteins when compared with the lean controls. Multiple logistic regression analysis revealed that amylin and HOMA-IR were significantly associated with the prevalence of ORG. In patients with ORG, proteinuria level correlated with amylin, total cholesterol, fasting insulin, and HOMA-IR. Moreover, proteinuria correlated positively with HOMA-IR and amylin in a multiple regression analysis. In addition, the endogenous creatinine clearance rate did not correlate with any metabolic marker. CONCLUSION: This study suggested that screening for HOMA-IR might have predictive value for renal damage in obese patients. In addition to insulin resistance, amylin also showed positive effects on evaluation of such renal impairment.

Osteopontin improves sensitivity to tyrosine kinase inhibitor in lung adenocarcinoma in vitro by promoting epidermal growth factor receptor phosphorylation.

PURPOSE: Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) improve the prognosis of lung adenocarcinoma (LUAD). However, the factors affecting its clinical efficacy remain unclear. This study aimed to determine the correlation between Osteopontin (OPN) and EGFR, and explore the inhibitory effect of first-generation TKI gefitinib on LUAD cells. METHODS: The correlation between OPN and EGFR was determined through bioinformatics technology, and the clinical information as well as samples of related patients were collected to verify the relationship between them. Using three different NSCLC cell lines A549, H1299 and PC9, we studied the effects of OPN expression and EGFR phosphorylation on the first-generation TKI's efficacy in vitro. RESULTS: Our data revealed that OPN staining positively linked to a more advanced clinical stage. Compared with the control group, LUAD cells with elevated OPN levels are more sensitive to the growth inhibitory effect of TKI. Knocking down of OPN decreased the response of cells to gefitinib. Besides, OPN also upregulated the phosphorylation of EGFR, thereby affecting the effect of TKI. CONCLUSION: OPN enhanced the sensitivity of LUAD cells to gefitinib by promoting EGFR phosphorylation. OPN may be a potential target for evaluating TKI efficacy and a potential target for molecular therapy.

Prognostic Factors Analysis and Nomogram Construction of Dual Primary Lung Cancer: A Population Study.

As a special type of lung cancer, multiple primary lung cancer (MPLC) has unique biological characteristics, and its research remains limited. The aim of our research was to identify prognostic factors and construct a prognostic nomogram of dual primary lung cancer (DPLC). A population cohort study of patients with DPLC was conducted using the extracted data from the Surveillance, Epidemiology, and End Results (SEER) database. Relevant survival variables were identified using the Cox proportional hazard model. Prognostic nomogram was performed and its predictive performance was validated via the modeling and validating cohort data. Additionally, propensity score matching (PSM) was also applied to evaluate whether surgery affected the OS of this study population. 5411 eligible DPLC patients were included in this study cohort, with 41.0% of 3-year OS rate and 27.7% of 5-year OS rate. Age, sex, race, grade, stage, lymph node (LN) metastasis, histological type, primary site, and surgery were considered to be prognostic factors of OS. The C-indexes of the established nomogram were 0.70 (95% CI (0.69, 0.71)) in the modeling group and 0.70 (95% CI (0.68, 0.72)) in the validation group, which showed an ideal model discrimination ability. AUC and calibration plots of 3- and 5-year OS also proved the good performance of the established nomogram. After 1 : 1 PSM, surgery can potentially reduce the risk of OS (HR = 0.63, 95% CI: 0.56-0.72) of DPLC. The prognostic nomogram with reliable performance was developed to predict 3- and 5-year OS rates, which could assist clinicians to make more reasonable survival prediction for DPLC patients. For patients without absolute surgical contraindications, surgery should be actively considered.

Effect of sustained intensive therapy with disease modifying anti-rheumatic drugs in rheumatoid arthritis: a 5-year real-world consecutive study.

BACKGROUND: Intensive therapy with disease modifying anti-rheumatic drugs (DMARDs) has been reported to improve the outcomes of rheumatoid arthritis (RA). However, real-world study on the effect of intensive therapy on RA sustained remission is still lacking. This study aimed to investigate the outcome of sustained intensive DMARD therapy (SUIT) for RA in a real-world 5-year consecutive cohort. METHODS: Based on a consecutive cohort of 610 out-patients with RA, remission of RA was assessed in 541 patients from 2012 to 2017, by dividing into SUIT, non-SUIT, and intermittent SUIT (Int-SUIT) groups. Changes in the disease activity scores were evaluated by 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), 28-joint disease activity score based on C-reactive protein (DAS28-CRP), and clinical deep remission criteria (CliDR). Cumulative remission rates between different groups were compared using Kaplan-Meier curves and predictive factors of sustained remission were identified by univariate and multivariate logistic regression analysis. RESULTS: The remission rates of the SUIT group decreased from 12.0% (65/541) to 5.6% (20/359) based on DAS28-ESR, from 14.0% (76/541) to 7.2% (26/359) based on DAS28-CRP, and from 8.5% (46/541) to 3.1% (11/359) based on CliDR, respectively, with a gradually decreasing trend during the 5 years. The SUIT regimen led to a significantly higher cumulative remission rate than non-SUIT regimen based on DAS28-ESR (39.7% vs. 19.5%, P = 0.001), DAS28-CRP (42.0% vs. 19.6%, P = 0.001), and CliDR (24.5% vs. 8.7%, P = 0.001). The cumulative remission rates of patients treated with SUIT regimen were significantly higher than those treated with Int-SUIT regimen based on DAS28-ESR (39.7% vs. 25.7%, P = 0.043) and CliDR (24.5% vs. 14.2%, P = 0.047), but there was no significant difference between the two groups based on DAS28-CRP (42.0% vs. 27.4%, P = 0.066). Multivariate logistic regression analysis showed that the use of SUIT regimen was an independent favorable predictor according to different remission definitions (for DAS28-ESR: odds ratio [OR], 2.215, 95% confidence interval [CI]: 1.271-3.861, P = 0.005; for DAS28-CRP: OR, 1.520, 95% CI: 1.345-1.783, P = 0.002; for CliDR: OR, 1.525, 95% CI: 1.314-1.875, P = 0.013). CONCLUSION: Sustained intensive treatment of RA is an optimal strategy in daily practice and will lead to an increased remission rate.

Clinical Practice Guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the Treatment of Rheumatoid Arthritis.

Tripterygium wilfordii Hook F (TwHF) is one of the most commonly used and effective traditional Chinese herbal medicines against rheumatoid arthritis (RA). Both Tripterygium Glycoside Tablets (TGT) and Tripterygium wilfordii Tablets (TWT) are the representative TwHF-based agents enrolled into the 2019 edition of Medicine Catalog for National Basic Medical Insurance, Injury Insurance, and Maternity Insurance. However, individual differences in TGT/TWT response across patients usually exist in the process of treating RA, implying that the clinical application of the two agents may not be standardized leading to the ineffective treatment and the risk of side effects. Growing evidence show that the bioactive constituents of TwHF may often have toxicity, the package insert of TGT and TWT may not be described in detail, and the therapeutic windows of the two agents are narrow. Thus, it is an urgent task to develop a standardized clinical practice guideline for TGT and TWT in the treatment of RA. In the current study, a group of clinical experts of traditional Chinese medicine and Western medicine in the research field of rheumatism diseases, pharmacists, and methodologists of evidence-based medicine were invited to select the clinical questions, to determine the levels of the evidence and the strength of the recommendations, and to develop the recommendations and good practice points. The guideline is formed based on the combination of clinical research evidence and expert experience (evidence-based, consensus, supplemented by experience). The clinical problems which are supported by clinical evidence may form recommendations, and the clinical problems without clinical evidence may form experts' suggestions. Both recommendations and experts' suggestions in this guideline summarized the clinical indications, usage, dosage, combined medication, and safety of TGT and TWT against RA systematically and comprehensively, which may offer a professional guidance in the context of the clinical application of the two TwHF-based agents.

Obesity-related glomerulopathy in China: a case series of 90 patients.

BACKGROUND: The epidemic of obesity has been paralleled by an increase in the incidence of chronic kidney disease. However, epidemiological data for obesity-related glomerulopathy (ORG) from developing countries, including China, are very limited. STUDY DESIGN: Case series. ORG defined as body mass index (BMI) of 28.0 kg/m(2) or greater; urinary protein excretion of 0.4 g/24 h or greater, and glomerulomegaly (glomerular volume > 3.27 x 10(6) microm(3)) with or without focal segmental glomerulosclerosis (FSGS). SETTING & PARTICIPANTS: 10,093 renal biopsy samples from patients obtained from February 2002 to November 2006 at the Research Institute of Nephrology, Nanjing University School of Medicine, China. PREDICTOR: Obesity defined as a BMI of 28.0 kg/m(2) or greater. Subjects were divided into 3 groups: mild-obesity group with BMI of 28.0 to less than 30 kg/m(2), moderate-obesity group with BMI of 30 to less than 35 kg/m(2), and severe-obesity group with BMI of 35 kg/m(2) or greater. OUTCOMES & MEASUREMENTS: Clinicoepidemiological and histopathologic characteristics of patients with ORG at the time of biopsy were described separately. RESULTS: ORG was observed in 90 biopsy specimens (0.89%); frequency increased from 0.62% to 1.0% during the last 5 years (P = 0.02). Mean age was 37.5 +/- 9.3 (SD) years, 67% were men, mean BMI was 31.2 +/- 3.3 kg/m(2), waist circumference was 103 cm (range, 89.4 to 124 cm) in men and 96.5 cm (range, 88.5 to 113 cm) in women, waist-hip ratio was 0.95 +/- 0.07, and 100% had visceral obesity. Of the total, 49%, 37%, and 14% had mild, moderate, and severe obesity, respectively. Mean urinary protein excretion of subjects was 1.48 +/- 1.2 g/24 h; 51%, 39%, and 10% had proteinuria with protein of 0.4 to 1.0, 1.0 to 3.5, and greater than 3.5 g/d, respectively. Mean measured creatinine clearance (Ccr) was 109 +/- 32.2 mL/min/1.73 m(2), with 42%, 36%, and 22% with a Ccr greater than 120, 90 to 120, and less than 90 mL/min/1.73 m(2), respectively. Glucose dysmetabolism, insulin resistance, dyslipidemia, and hypertension were observed in 77%, 88%, 76%, and 63% of patients, respectively. FSGS was observed in 70%. Mean foot-process width was 534 +/- 176 nm. Foot-process fusion was seen in 36% of patients. Greater BMI was associated with greater proteinuria (P < 0.02), greater Ccr (P < 0.03), and greater foot-process width (P < 0.04). LIMITATIONS: Inability to compute prevalence or incidence from case series. BMI was calculated at time of renal biopsy. CONCLUSIONS: Most patients with ORG had mild obesity, visceral obesity, minor proteinuria, preserved Ccr, and FSGS.

Loss of Smad7 Promotes Inflammation in Rheumatoid Arthritis.

Objective: Smad7 is an inhibitory Smad and plays a protective role in many inflammatory diseases. However, the roles of Smad7 in rheumatoid arthritis (RA) remain unexplored, which were investigated in this study. Methods: The activation of TGF-ß/Smad signaling was examined in synovial tissues of patients with RA. The functional roles and mechanisms of Smad7 in RA were determined in a mouse model of collagen-induced arthritis (CIA) in Smad7 wild-type (WT) and knockout (KO) CD-1 mice, a strain resistant to autoimmune arthritis induction. Results: TGF-ß/Smad3 signaling was markedly activated in synovial tissues of patients with RA, which was associated with the loss of Smad7, and enhanced Th17 and Th1 immune response. The potential roles of Smad7 in RA were further investigated in a mouse model of CIA in Smad7 WT/KO CD-1 mice. As expected, Smad7-WT CD-1 mice did not develop CIA. Surprisingly, CD-1 mice with Smad7 deficiency developed severe arthritis including severe joint swelling, synovial hyperplasia, cartilage damage, massive infiltration of CD3+ T cells and F4/80+ macrophages, and upregulation of proinflammatory cytokines IL-1ß, TNFα, and MCP-1. Further studies revealed that enhanced arthritis in Smad7 KO CD-1 mice was associated with increased Th1, Th2 and, importantly, Th17 over the Treg immune response with overactive TGF-ß/Smad3 and proinflammatory IL-6 signaling in the joint tissues. Conclusions: Smad7 deficiency increases the susceptibility to autoimmune arthritis in CD-1 mice. Enhanced TGF-ß/Smad3-IL-6 signaling and Th17 immune response may be a mechanism through which disrupted Smad7 causes autoimmune arthritis in CD-1 mice.

Podocyte lesions in patients with obesity-related glomerulopathy.

BACKGROUND: Obesity-related glomerulopathy is an important complication of obesity that shares some pathophysiological factors relevant to renal damage with diabetic nephropathy. It was recognized that podocyte lesions lead to proteinuria and glomerulosclerosis in patients with some proteinuric glomerular diseases, especially diabetic nephropathy. However, podocyte changes in patients with obesity-related glomerulopathy and the underlying mechanisms are unclear. METHODS: Glomerular volume, podocyte number, and foot-process width were evaluated in 46 patients with biopsy-proven obesity-related glomerulopathy. Renal tissue from 10 kidney donors served as controls. RESULTS: Glomerular volume was enlarged markedly in patients with obesity-related glomerulopathy (P < 0.001), with a corresponding decrease in podocyte density (P < 0.001) compared with controls. Foot-process width on the peripheral glomerular basement membrane was increased significantly, whereas mesangial volume fraction did not differ between patients with obesity-related glomerulopathy and controls. Degree of proteinuria was associated strongly with decreased podocyte density (P = 0.001), increased foot-process width (P = 0.001), and decreased podocyte number (P = 0.002). In addition, the endogenous creatinine clearance rate correlated with decreased podocyte number (P = 0.008). Interestingly, podocyte number and density correlated significantly with abnormalities in fasting glucose (P < 0.001) and insulin levels (P < 0.001) and Homeostasis Model Assessment of Insulin Resistance (P < 0.001). CONCLUSION: Decreased podocyte density and number were observed in patients with obesity-related glomerulopathy, and changes in podocytes correlated with degree of proteinuria and renal function impairment in these patients. In addition to the enlargement in glomerular volume with consequential mechanical stretch, metabolic disorders also may contribute to the development of podocyte lesions in patients with obesity-related glomerulopathy.

[Recognition and study of susceptible gene to ankylosing spondylitis].

To study the potential correlations between variances of TNFalpha gene and onset of ankylosing spondylitis in Chinese population, We scanned and analyzed the promoters of TNFalpha genes in 75 AS patients from south of China and found -850 T mutation allele frequency rather high (39.3%).By case-control study, the distribution of TT genotype is significantly higher in AS patients than that in normal subjects (10.7% VS 2.1%,P=0.003); Mutation T allele has a remarkable difference between AS group and normal control (72.2% vs 21.4%,P=2.729 x 10(-9)). The difference in distribution of TX genotype and non -TX genotype is also significant statistically between different genders(male: P=3.42 x 10(-9);female: P=0.001). The result suggests that this variation has a strong association with AS in males and females. No similar reports about the association between AS and the T mutation allele have been acquired. Therefore, our hypothesis can be supported by our results on the whole and the -850 C-->T mutation allele in the region on promoter of TNFalpha gene is likely one of susceptible genes to AS.

Association of OPG gene polymorphism with susceptibility to rheumatoid arthrits in Chinese Han.

AIM: To investigate the association of osteoproterin (OPG) gene polymorphisms 163A/G (rs3102735), 245T/G (rs3134069) with susceptibility to rheumatoid arthritis (RA) in Chinese Han population. OBJECTIVE: To study the correlation between the disease of rheumatoid arthritis (RA) in Chinese Han group and the association of osteoproterin (OPG) gene polymorphisms 163A/G(rs3102735) and 245T/G (rs3134069). Approaches: 205 RA patients and 171 healthy control subjects were participated into this study. Genotype analysis was conducted by polymerase chain reaction-based restriction fragment length polymorphism and was subsequently confirmed by DNA sequencing. Odd ration (OR) and 95% confidence intervals (95% CI) were calculated for the risk of genotype and allele. CONSEQUENCES: OPG gene polymorphisms 163A/G, 245T/G conformed to the Hardy-Weinberg equilibrium. The statistical differences in genotype of AA, AG, GG at 163A/G locus were founded in RA and controls. The G allele was associated with an increased risk of RA, with OR 1.219 (95% CI: 1.066-2.339). According to the observation, there are no significant differences between the RA and control groups with respect to genotype and allele frequencies of OPG gene 245T/G (χ(2)=0.734, 0.518, p>0.05). CONCLUSION: The OPG gene 163A/G SNP may be associated with the susceptibility of RA, G allele may be the risk factor for the development of RA.

Polyphenols in Regulation of Redox Signaling and Inflammation During Cardiovascular Diseases.

Cardiovascular diseases remain one of the major health problems worldwide. The worldwide research against cardiovascular diseases as well as genome wide association studies were successful in indentifying the loci associated with this prominent life-threatening disease but still a substantial amount of casualty remains unexplained. Over the last decade, the thorough understanding of molecular and biochemical mechanisms of cardiac disorders lead to the knowledge of various mechanisms of action of polyphenols to target inflammation during cardiac disorders. The present review article summarizes major mechanisms of polyphenols against cardiovascular diseases.

[Needle biopsy of spondyloarthropathy: pathological features and clinical significance].

OBJECTIVE: To study the pathological features of sacroiliitis, aiming at improving the early diagnosis of ankylosing spondylitis (AS). METHODS: CT guided needle biopsy of sacroiliac joint (SIJ) was performed in 96 cases of spondyloarthropathy (SpA) patients with 3 autopsy materials of non-SpA sacroiliac joints serving as control. Pathological features were studied by two independent observers. Clinical data were collected and analyzed. RESULTS: No pathological change was noticed in the control group. Among the 96 cases of SpA, pathological changes were found in 76 cases, including bone marrow inflammation, pannus formation, subchondral bony plate destruction, cartilage degeneration/erosion, synovitis, and enthesitis. The aforementioned first 4 findings were present in 45 cases of grade 0/I CT sacroiliitis. In the synovial specimens obtained, synovitis was seen in some cases of grade I and all of >/= grade II CT sacroiliitis,while no inflammatory change was noticed in all cases of grade 0 CT sacroiliitis. Frequency rate of cartilage erosion and ossification in grade 0/I CT sacroiliitis was the lowest in comparison with the other groups. Moreover, in cases of grade 0/I CT sacroiliitis, cartilage erosion only present at the bony plate side, while the joint cavity side was not affected. The inflammatory index was significantly lower in cases of grade IV CT sacroiliitis than that in the other groups. Enthesitis only presented in some cases of >/= grade II CT sacroiliitis. Among the 65 undifferentiated spondyloarthropathy patients, 45 were diagnosed as AS after SIJ pathological examination. The mean disease duration of these 45 cases was significantly shorter than that in cases of >/= grade II CT sacroiliitis. CONCLUSIONS: Inflammatory changes of SIJ did exist in cases of the < grade II CT sacroiliitis. Sacroiliitis probably initiated with bone marrow inflammation, followed by pannus formation, subchondral bony plate destruction, and cartilage degeneration/erosion, eventually leading to fibrosis, ossification and joint fusion. Synovitis and enthesitis were not the very early changes of sacroiliitis. Pathological examination was beneficial to the early diagnosis and differential diagnosis of ankylosing spondylitis.

Catalytic conversion of bio-oil to oxygen-containing fuels by simultaneous reactions with 1-butanol and 1-octene over solid acids: Model compound studies and reaction pathways.

Upgrading bio-oil by addition reactions across olefins represents a route to refine bio-oil to combustible and stable oxygen-containing fuels. Development and application of highly active strong solid acid catalysts with good hydrothermal stability has become a key determinant for success, because bio-oil's complexity includes large amounts of water. Temperatures of 120°C or more are needed for satisfactory kinetics. Batch upgrading of a model bio-oil (phenol/water/acetic acid/acetaldehyde/hydroxyacetone/d-glucose/2-hydroxymethylfuran) over five water-tolerant solid acid catalysts (Dowex50WX2, Amberlyst15, Amberlyst36, silica sulfuric acid (SSA) and Cs(2.5)H(0.5)PW(12)O(40) supported on K-10 clay (Cs(2.5)/K-10, 30wt.%)) with 1-octene/1-butanol were studied at 120°C/3h. SSA, , exhibited the highest water tolerance and activity. Upgrading using olefin/1-butanol is complex, involving many simultaneous competing esterification, etherification, olefin hydration, phenol alkylation, aldol condensation, sugar dehydration etc. reactions.

Challenge in pathologic diagnosis of Alport syndrome: evidence from correction of previous misdiagnosis.

BACKGROUND: Pathologic studies play an important role in evaluating patients with Alport syndrome besides genotyping. Difficulties still exist in diagnosing Alport syndrome (AS), and misdiagnosis is a not-so-rare event, even in adult patient evaluated with renal biopsy. METHODS: We used nested case-control study to investigate 52 patients previously misdiagnosed and 52 patients initially diagnosed in the China Alport Syndrome Treatments and Outcomes Registry e-system. RESULTS: We found mesangial proliferative glomerulonephritis (MsPGN, 26.9%) and focal and segmental glomerulosclerosis (FSGS, 19.2%) were the most common misdiagnosis. FSGS was the most frequent misdiagnosis in female X-linked AS (fXLAS) patients (34.8%), and MsPGN in male X-linked AS (mXLAS) patients (41.2%). Previous misdiagnosed mXLAS patients (13/17, 76.5%) and autosomal recessive AS (ARAS) patients (8/12, 66.7%) were corrected after a second renal biopsy. While misdiagnosed fXLAS patients (18/23, 78.3%) were corrected after a family member diagnosed (34.8%) or after rechecking electronic microscopy and/or collagen-IV alpha-chains immunofluresence study (COL-IF) (43.5%) during follow-up. With COL-IF as an additional criterion for AS diagnosis, we found that patients with less than 3 criteria reached have increased risk of misdiagnosis (3.29-fold for all misdiagnosed AS patients and 3.90-fold for fXLAS patients). CONCLUSION: We emphasize timely and careful study of electronic microscopy and COL-IF in pathologic evaluation of AS patients. With renal and/or skin COL-IF as additional criterion, 3 diagnosis criteria reached are the cutoff for diagnosing AS pathologically.