Altered serum cytokine expression profile in systemic sclerosis and its regulatory mechanisms / 北京大学学报(医学版)

OBJECTIVE@#To analyze the expression profile of serum cytokines in patients with systemic sclerosis (SSc) and explore its possible regulatory mechanisms.@*METHODS@#Serum and DNA of peripheral blood mononuclear cells were collected from 30 SSc patients and 80 normal controls (NCs). According to the presence or absence of interstitial lung disease (ILD) in SSc, the patients were divided into SSc with ILD group and SSc without ILD group. According to the degree of skin involvement, the patients were divided into diffuse systemic scleroderma (dcSSc) group and limited systemic scleroderma (lcSSc) group. According to the presence of anti-topoisomerase-1 antibody (anti-Scl-70 antibody) in the serum of patients with SSc, they were divided into SSc Scl-70 (+) group and SSc Scl-70 (-) group. 27 cytokines in serum were detected by Luminex MAGPIX detection system and Bio-Plex Pro Human Cytokine 27-plex Assay kit: interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12P70, IL-13, IL-15, IL-17, basic fiber growth factor (BASIC FGF), eotaxin, granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), interferon-gamma induced protein 10(IP-10), monocyte chemotactic protein 1(MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein 1β(MIP-1β), platelet-derived growth factor BB (PDGF-BB), regulated on activation in normal T-cell expressed and secreted (RANTES), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor(VEGF). Methylation sites were detected by Illumina 450K methylation chip.@*RESULTS@#Compared with NCs group, the expression of 12 cytokines (BASIC FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IL-1β, IL-1ra, IL-6, IP-10, MCP-1, TNF-α and RANTES) in the SSc group significantly increased (P<0.05), IL-5 was decreased expression in the SSc group (P<0.05), there was no significant difference in the expressions of the other 14 cytokines. Compared with lcSSc group, 9 cytokines (eotaxin, IL-5, MCP-1, IL-2, RANTES, IL17A, IL-8, MIP-1β and PDGF-BB) increased in dcSSc group, but there was no significant difference. Compared with SSc without ILD group, IL-15 increased in SSC with ILD group [18.2 (172.97) ng/L vs. 2.03(0.05) ng/L, P<0.05]. Compared with SSc Scl-70 (-) group, the expression of IP-10 decreased in SSc Scl-70 (+) group [1 030 (2 196.6) ng/L vs. 1 878 (2 964) ng/L, P<0.05]. The correlation analysis of serum cytokines with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) showed that IL-6 was positively correlated with ESR (r =0.04, P= 0.017), MCP-1 (r=0.49, P=0.043) and MIP-1β (r=0.41, P=0.007) positively correlated with CRP. By analyzing the changes of methylation sites of cytokines, it was found that cg17744604 in IL-10 TSS1500 region, cg06111286 in IL-12P70 TSS200 region, cg07935264 in IL-1β TSS200 region, cg01467417 in IL-1ra TSS1500 region, cg03989987 in IL-1ra 5'UTR region and cg21099624 in VEGF TSS200 region were all hypomethylated.@*CONCLUSION@#There were different cytokines expression profiles in the serum of SSc patients, and the altered cytokines were correlected with the degree of skin damage and pulmonary fibrosis. Many cytokines were regulated by methylation.

Clinical analyses of 66 cases of mid-trimester pregnancy termination in women with prior cesarean / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The rate of cesarean delivery has significantly increased in China in the last decade. Women with prior cesarean history tend to have a higher risk of uterine rupture during termination of the pregnancy in mid-trimester than those without such a history. The aim of our study was to evaluate the influences of the potential risk factors on uterine rupture in women with prior cesarean.</p><p><b>METHODS</b>We conducted this retrospective study of women with prior cesarean section, who underwent mid-trimester pregnancy termination between January 2006 and December 2013 in Peking Union Medical College Hospital. The protocol was oral administration of mifepristone and misoprostol for the patients with the gestational ages below 16 weeks or intra-amniotic injection of ethacridine lactate (EL) for those with at least 16 weeks of gestational ages. The thickness of the lower uterine segment (LUS) was measured before the termination of pregnancy. Logistic regression was used to study the risk factors of uterine rupture.</p><p><b>RESULTS</b>The total rate of successful abortion was 93.9% (62/66). Four patients failed in induction, and one of them received curettage, whereas the other three experienced uterine rupture (4.5%). The successful rates of abortion were 85.7% (30/35) for women treated with mifepristone-misoprostol and 86.1% (31/36) for those treated with EL. There was a significant difference in the mean LUS thickness between the uterine rupture group (3.0 ± 2.0 mm) and the nonrupture group (7.0 ± 3.0 mm) (P < 0.05). The LUS thickness of <3 mm was associated with uterine rupture during mid-trimester pregnancy termination in women with prior cesarean (odds ratio, 94.0; 95% confidence interval 4.2-2106.1) after adjusted maternal age, gestational age, interdelivery interval and prior cesarean section. Severe bleeding that required transfusion occurred in one case (1.5%).</p><p><b>CONCLUSIONS</b>Both the mifepristone-misoprostol and the EL regimens were effective and safe for the termination of mid-trimester pregnancy in women with prior cesarean. A thinner LUS is associated with a relatively high risk of uterine rupture.</p>

Pregnancy Outcomes of In Vitro Fertilization with or without Ovarian Hyperstimulation Syndrome: A Retrospective Cohort Study in Chinese Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The effect of ovarian hyperstimulation syndrome (OHSS) on pregnancy outcomes of in vitro fertilization (IVF) patients is still ambiguous. This study aimed to analyze pregnancy outcomes of IVF with or without OHSS in Chinese patients.</p><p><b>METHODS</b>A retrospective cohort study was undertaken to compare pregnancy outcomes between 190 women with OHSS and 197 women without OHSS. We examined the rates of clinical pregnancy, multiple pregnancies, miscarriage, live birth, preterm delivery, preterm birth before 34 weeks' gestation, cesarean delivery, low birth weight (LBW), and small-for-gestational age (SGA) between the two groups. Odds ratios (OR s) and 95% confidence intervals (CI s) of measure of clinical pregnancy were also analyzed.</p><p><b>RESULTS</b>The clinical pregnancy rate of OHSS patients was significantly higher than that of non-OHSS patients (91.8% vs. 43.5%, P < 0.001). After controlling for drug protocol and causes of infertility, the adjusted OR s of moderate OHSS and severe/critical OHSS for clinical pregnancy were 4.65 (95% CI, 1.86-11.61) and 5.83 (95% CI, 3.45-9.86), respectively. There were no significant differences in rates of multiple pregnancy (4.0% vs. 3.7%) and miscarriage (16.1% vs. 17.5%) between the two groups. With regard to ongoing clinical pregnancy, we also found no significant differences in the rates of live birth (82.1% vs. 78.8%), preterm delivery (20.9% vs. 17.5%), preterm birth before 34 weeks' gestation (8.6% vs. 7.9%), cesarean delivery (84.9% vs. 66.3%), LBW (30.2% vs. 23.5%), and SGA (21.9% vs. 17.6%) between the two groups.</p><p><b>CONCLUSION</b>OHSS, which occurs in the luteal phase or early pregnancy in IVF patients and represents abnormal transient hemodynamics, does not exert any obviously adverse effect on the subsequent pregnancy.</p>

Research advances on ubiquitin C-terminal hydrolase in oncogenesis and progression / 浙江大学学报·医学版

By regulating the ubiquitination and deubiquitination of key proteins, ubiquitin-proteasome system mediates a variety of cellular activities. Ubiquitin C-terminal hydrolase (UCH) is a deubiquitinating enzyme which can remove ubiquitin chains at the end of ubiquited proteins. The abnormal expression of UCH has been found in a variety of tumor tissues, indicating that it participates in the process of tumor development. Here we review the characteristics of UCH members and current understanding about the role of UCH in tumor development, and the potential target for cancer treatment.

Research progress on ubiquitin-specific protease in antiviral immunity / 浙江大学学报·医学版

Ubiquitin-specific protease(USP), which belongs to cysteine protease, is an important member of the deubiquitinating enzyme family(DUB). USP plays an important role in the immune response against viral infections, in which it can regulate the production of type I interferon through various ways to initiate or weaken the antiviral immune response. USP2b, USP3, USP18, USP25, UL36USP and HAUSP play a role of antivirus; while USP4, USP13, USP15 and USP17 negatively regulate antiviral immune response. In this article we review the recent progress on roles of USP family in antiviral immune response.

The relationship of long-term school milk consumption and their attention, cognitive ability among children / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the status of attention and cognitive ability among children who consumed school milk for relative long-term period.</p><p><b>METHODS</b>From July to August 2009, a cluster of 435 children aged 10-12 year-old (including 188 boys and 247 girls) were sampled in Changsha, Hunan Province and divided into two groups, which were long-term milk-consumption group (the children drank school milk four times per week and continued for over one year or one to three times per week and continued for over three years, 220 cases) and seldom milk-consumption group (the others, 215 cases). Children's growth and anemia status were evaluated, the mental work ability index (IMC) was evaluated by Alimov searching table and both the attention and memory function of children were evaluated by clinical memory scale.</p><p><b>RESULT</b>The average height, hemoglobin (Hb) concentration and anemia rate in long term milk-consumed group were (147.6 ± 8.1) cm, (40.1 ± 9.0) g/L and 7.1% (15/212), and the indexes of the seldom milk-consumed group were (145.9 ± 8.3) cm, (38.7 ± 10.0) g/L and 13.3% (27/203). There were significant statistical differences (t = 2.124, 2.621; χ(2) = 4.418, all P values < 0.05). The scores of the third IMC in the long term milk-consumed group (233.6 ± 44.1) were higher than the seldom milk-consumed group (222.8 ± 42.3), (t = 2.505, P < 0.05). The scores of picture free recall (14.7 ± 5.0) and memory quotient (86.7 ± 17.2) were higher than that in the seldom milk-consumed group (13.4 ± 4.8 and 82.7 ± 16.1 respectively) (t = 2.539, 2.433; all P values < 0.05).</p><p><b>CONCLUSION</b>Drinking milk for long-term can help increasing attention and memory of children.</p>