1.Effect and mechanism of rosuvastatin on the expression of tissue factor in cultured human monocytemacrophages cell induced by oxidized low density lipoprotein
Haibin SONG ; Yu ZHANG ; Kunping GUAN ; Xiaoyu SHEN ; Feng ZHAO
Journal of Chinese Physician 2012;14(2):173-176
ObjectiveTo investigate the effects and mechanism of rosuvastatin on the expression of tissue factor in cultured human monocyte-macrophages cells which was induced by oxidized low density lipoprotein(ox-LDL).MethodsThe human monocyte-macrophages cells were divided into four groups:control group,ox-LDL group,Poly-inosine monophosphate (Poly Ⅰ) group,rosuvastatin group.The expression of LOX-1mRNA and TF mRNA was assayed by RT-PCR.The ELISA was performed to determine the protein concentration of TF.ResultsCompared with control group,the expression of LOX-1 mRNA and TF mRNA was increased in the ox-LDL group[ (3.25156±0.15772) vs (1±0) ; (2.522451±0.138967) vs (1±0) ],and it was in a concentration-dependent manner (P<0.01).Compared with the expression of LOX-1 mRNA in the Poly-inosine monophosphate group and rosuvastatin group,TF mRNA were decreased in the ox-LDL group[ (2.95139±0.157253) vs(3.25156±0.15772) ; (2.877343±0.156558) vs(3.25156±0.15772) ; (1.811956±0.169699) vs (2.522451±0.138967) ; (1.687701±0.174647) vs (2.522451±0.138967)],and it was in a concentration-dependent manner(P<0.05).Compared with control group,the expression of TF in the ox-LDL group was increased [(207.7233±1.154701) vs (184.8467±0.871799) ],and it was in a concentration-dependent manner (P<0.01).Compared with the Poly-inosine monophosphate group and rosuvastatin group [(197.8733±1.505003) vs (207.7233±1.154701) ;(202.9567±2.722744)vs(207.7233±1.154701) ],the expression of TF in the ox-LDL group were decreased,and it was in a concentration-dependent manner (P<0.05).ConclusionsLOX-1 may be responsible for the expression of TF in human monocyte-macrophages cells induced by ox-LDL.Rosuvastatin is able to down-regulate the expression of LOX-1mRNA in human monocyte-macrophages cells through oxLDL,and TF mRNA and TF expression can be reduced.
2.Effects of beraprost sodium on serum levels of soluble adhesion molecule-1 and C-reactive protein and urinary albumin excretion rate in patients with early diabetic nephropathy
Juan HUANG ; Shaoying ZHANG ; Xiaoyu DUAN ; Sisi GUAN
Clinical Medicine of China 2013;(5):512-514
Objective To observe the clinical efficacy of beraprost sodium on early stage of diabetic nephropathy(DN).Methods We measured serum levels of serum soluble intercelluhar adhesion molecule (sICAM)-1 in 27 cases with diabetes without nephropathy and 48 cases with early DN.Patients with early DN were randomly assigned into two treatment groups:the conventional treatment group and the beraprost sodium treatment group.Changes of sICAM-1 and C-reactive protein (CRP) levels and urinary albumin excretion rate (UAER) were measured in the two groups before and after treatment.Results The serum sICAM-1 levels in early DN patients was significantly higher than that of the diabetes without nephropathy group((1385 ± 171) g/ Lvs.(943 ± 167) g/L;t =1.034,P =0.002).There were no significant difference observed on levels of sICAM-1,CRP and UAER between the two treatment groups (P > 0.05).The level of sICAM-1 and CRP in the beraprost sodium treatment group was significantly lower than those before treatment (P < 0.05 or P < 0.01).The symptoms were significantly alleviated in both groups (P < 0.05 or P < 0.01),especially for the beraprost sodium treatment group(P < 0.05 or P < 0.01).Conclusion Patients with early DN have elevated serum sICAM-1 levels.Treatment of beraprost sodium has protective effect on early DN as it significantly decreases the serum levels of sICAM-1 and CRP in patients with early DN.
3.Sequence analysis of LEAFY homologous gene from Dendrobium moniliforme and application for identification of medicinal Dendrobium.
Wenrui XING ; Beiwei HOU ; Jingjiao GUAN ; Jing LUO ; Xiaoyu DING
Acta Pharmaceutica Sinica 2013;48(4):597-603
The LEAFY (LFY) homologous gene of Dendrobium moniliforme (L.) Sw. was cloned by new primers which were designed based on the conservative region of known sequences of orchid LEAFY gene. Partial LFY homologous gene was cloned by common PCR, then we got the complete LFY homologous gene Den LFY by Tail-PCR. The complete sequence of DenLFY gene was 3 575 bp which contained three exons and two introns. Using BLAST method, comparison analysis among the exon of LFY homologous gene indicted that the DenLFY gene had high identity with orchids LFY homologous, including the related fragment of PhalLFY (84%) in Phalaenopsis hybrid cultivar, LFY homologous gene in Oncidium (90%) and in other orchid (over 80%). Using MP analysis, Dendrobium is found to be the sister to Oncidium and Phalaenopsis. Homologous analysis demonstrated that the C-terminal amino acids were highly conserved. When the exons and introns were separately considered, exons and the sequence of amino acid were good markers for the function research of DenLFY gene. The second intron can be used in authentication research of Dendrobium based on the length polymorphism between Dendrobium moniliforme and Dendrobium officinale.
4.The effect of fasudil via Rho/ROCK signaling pathway on the inflammation and fibrosis in human mesangial cells in high glucose medium
Dongwei MA ; Qiuyue WANG ; Xiaoyu MA ; Jing LI ; Qinghua GUAN ; Yu FU
Chinese Journal of Internal Medicine 2011;50(7):580-584
Objective To study the effect of fasudil on inhibiting the Rho/ROCK signaling pathway under high glucose in human mesangial cells (HMCs) inflammation and fibrosis. Methods Synchronized HMCs were divided into following groups: (1) Normal glucose control group ( NG, 5. 5 mmol/L glucose) ;(2) High glucose group (HG, 30 mmol/L glucose) ; (3) Mannitol group (Man, 5.5 mmol/L glucose + 24. 5 mmol/L mannitol) ; (4) High glucose + fasudil group ( HG + F, the concentrations of fasudil were 25 ,50 and 100 μmol/L, respectively). Collect the supernatant and cells at 0, 12, 24, 36, 48 and 72 h respectively, and determine the concentration changes of the RhoA, ROCK- Ⅰ, connective tissue growth factor (CTGF)mRNA with real-time PCR method in the cells, then used the ELISA method to check the protein content of the fibronectin ( FN) , CTGF, TNFα in the supernatant. Results ( 1) RhoA, ROCK- Ⅰand CTGF mRNA of the HMCs cultured under the high glucose expressed significantly higher than those in the normal group, and there was certain time-dependence. Besides, there was no statistic significance by comparing Man and NG. (2) Under the high glucose situation, after the fasudil pretreatment with different concentrations and 24 h or 48 h culture with high glucose, RhoA, ROCK- Ⅰ , CTGF mRNA expression was significantly decreased in HG + F, compared with HG, and there was certain concentration-dependence. (3) High glucose increased the FN, CTGF, TNFα protein secretion of HMCs in a time-dependent manner, but normal glucose and mannitol had no such effect. (4) After the fasudil pretreatment with different concentrations and culture with high glucose for 12, 24, 36, 48, 72 h, the FN, CTGF, TNFα protein secretion was significantly reduced compared with HG. Conclusion Fasudil can reduce the secretion of downstream inflammatory factors and cytokines by inhibiting high glucose-activated HMCs Rho/ROCK signaling pathway, and reduce the inflammation and fibrosis of HMCs. This provides a new basis for the therapeutic target in the treatment of diabetic nephropathy.
5.Analysis of clinical pathology of the IgA nephropathy and purpura nephritis in children from the perspective of IgA vasculitis
Cuirong DUAN ; Huijie XIAO ; Xuhui ZHONG ; Fang WANG ; Na GUAN ; Xiaoyu LIU ; Jie DING
Journal of Clinical Pediatrics 2015;(6):511-514
Objectives To analysis clinical pathology of organ speciifc IgA vasculitis (IgA nephropathy) and systemic IgA vasculitis (allergic purpura) of purpura nephritis in children. Methods Clinical and pathological data of hospitalized pediatric patients of IgA nephropathy and purpura nephritis were retrospectively analyzed from June 1993 to November 2014. Results There were 405 patients of IgA nephropathy (256 males and 149 females). The ratio of male to female was 1.7:1. The average age was 10.2±2.8 years. The nephrotic syndrome (31.6%) was the most common clinical type, followed by hematuria and proteinuria (27.9%). There were 548 patients of purpura nephritis, 329 males and 219 females. The ratio of male to female was 1.5:1. The average age was 10.2±3.1 years. The hematuria and proteinuria (61.6%) was the most common clinical type, followed by nephrotic syndrome (21.4%). None of the IgA nephropathy progressed to systemic vasculitis (allergic purpura). Conclusions The causes, onset ages and clinical manifestations of IgA nephropathy and allergic purpura may be consistent or overlap, but none of IgA nephropathy (organ speciifcity IgA vasculitis) progressed to allergic purpura (systemic IgA vasculi-tis). IgA nephropathy might have more renal immune disorder mechanisms involved in its pathogenesis.
6.Heritability of cognitive functions in nuclear families with bipolar I disorder
Jianshan CHEN ; Ting ZHOU ; Lijie GUAN ; Xiaoyu HAO ; Xuan LI ; Liping CAO ; Chanjuan YANG
Chinese Journal of Nervous and Mental Diseases 2018;44(2):85-89
Objective To examine the heritability of neurocognitive functions in bipolar I disorder(BD-I)families and BD-associated cognitive endophenotypes. Methods Seventy-nine nuclear families consisting of euthymic BD-I probands and their healthy parents were recruited. Cognitive functions including attention, working memory, processing speed and executive function were evaluated by 7 classic neurocognitive tests, and the heritability of neuroconitive functions in these families was estimated using parent-offspring regression indexes of quantitative traits.Furthermore,the heritable cognitions were compared between 79 BD probands and 140 normal controls. Results After adjusted by age and education,mistake numbers of Trail Making Test A(TMT-A),total score and completed mission numbers of Tower of Hanoi (TOH) were significantly heritable (P<0.05). The comparison of these heritable cognitions between patients and normal controls showed that TOH total score and TOH completed mission numbers were significantly impaired in the patient group (P<0.05). Conclusion Processing speed and executive function are probably heritable in BD nuclear families. Executive function impairments may be disease-related which could be candidate endophenotypes for bipolar disorder.
7.Investigation and analysis of somatic symptom disorder and anxiety and depression in patients with myocardial bridge
Bingxu CHEN ; Yixuan LI ; Yuzhuo LIU ; Xiaoyu GUAN ; Meng JIANG ; Jialiang MAO
Chinese Journal of Behavioral Medicine and Brain Science 2020;29(2):130-135
Objective:To investigate and analyze the somatic symptom disorder, anxiety and depression in patients with myocardial bridge.Methods:A total of 276 patients with myocardial bridge diagnosed by coronary angiography (CAG) were enrolled in the department of cardiology of Renji hospital in Shanghai from June to December in 2016. There were 151 cases of simple myocardial bridge (no coronary stenosis or coronary artery stenosis <30%) and 125 cases of complex myocardial bridge (combined with coronary stenosis >30%). A total of 1067 patients with myocardial bridge without coronary angiography were collected at the same time. Self-rating somatic symptom scale (SSS), generalized anxiety disorder (GAD-7) and patient health questionnaire (PHQ -9) were given to these patients during hospitalization. At the same time, somatic symptoms disorder and anxiety and depression in the myocardial bridge group and non-myocardial bridge group were compared.Results:The prevalence of somatic symptom disorder in patients with myocardial bridge was higher than that in non-myocardial bridge patients (35.86% vs 28.30%, P<0.05). There was significant correlation between somatic symptom disorder and depression and anxiety, with correlation coefficients of 0.629 and 0.565, respectively. The prevalence of depression and anxiety in myocardial bridge patients was higher than that in non-myocardial bridge patients (depression: 23.91% vs 22.11%. P=0.467; anxiety: 17.02% vs 14.15%, P=0.22), but there was no statistical difference. For male patients or female patients, the prevalence of somatic symptom disorder, depression and anxiety in the simple myocardial bridge patients were higher than those in the complex myocardial bridge patients, but there was no statistical difference. The most common non-specific somatic symptoms disorder in patients with myocardial bridge were fatigue (64.5%), followed by sleep disorders (63.8%) and decreased attention (63.0%). Conclusion:The somatic symptom disorder in patients with myocardial bridge is significantly higher than that in non-myocardial bridge group. Especially for patients with myocardial bridge with non-specific somatic symptoms, early identification of somatic symptoms disorder of myocardial bridge patients will be beneficial to proper clinical invitation.
8.Predictors for muscle invasion of upper tract urothelial carcinoma
Xuhui GUAN ; Jingmin CUI ; Zhe ZHANG ; Xiaoyu LIU ; Baomin QIAO
Chinese Journal of Urology 2023;44(4):259-264
Objective:To explore the predictors of upper tract urothelial carcinoma (UTUC) invading muscle.Methods:The preoperative clinical data of 169 patients with UTUC who underwent radical nephroureterectomy (RNU) in the Department of Urology, Second Hospital of Tianjin Medical University from August 2019 to September 2021 were retrospectively collected. The average age of the patients was (67.7±8.3)years. There were 95 male cases (56.2%).15 cases (15.8%) were with diabetes, 46 cases (48.4%) with hypertension, 68 cases (71.6%) with hematuria, 44 cases (46.3%) with renal pelvis tumor, 74 cases (77.9%) with hydronephrosis and 8 cases (8.4%) with multifocality. There were 15 (20.3%), with diabetes, 40(54.1%) with hypertension, 58(78.4%)with hematuria, 32(43.2%) with renal pelvis tumor, 60(81.1%) with hydronephrosis and 2(2.7%) with multifocality among 74 female patients(43.8%), respectively. Patients’ body mass index (BMI) was (24.2±3.2) kg/m 2.The tumor diameter was (3.4±1.8) cm. The average count of neutrophil (NEU) was (4.2±1.7) ×10 9/L, with monocyte (MON) (0.4±0.2) ×10 9/L, platelet (PLT) (237.8±75.3) ×10 9/L and lymphocyte (LYM) (1.7±0.5) ×10 9/L. Neutrophil-to-lymphocyte ratio (NLR) was 2.7±1.4. Mmonocyte-to-lymphocyte ratio (MLR) was 0.3±0.1 and platelet-to-lymphocyte ratio (PLR) was 151.1±59.6. The concentrations of hemoglobin (Hb) and fibrinogen (FIB) were (127.1±18.3) g/L and(3.5±1.0) g/L. Univariate logistic regression analysis was performed on all preoperative data, and a nomogram was established to predict UTUC invading muscle by stepwise regression combined with multivariate logistic analysis. Concordance index (C-index) was used to evaluate the accuracy of the model, and Hosmer-Lemeshow test was used to check the fit. Using 1000 bootstrap resampling to validate the model and draw calibration plot. Receiver operating characteristics (ROC) curves were used to determine the most appropriate cut-off point of the model to predict tumor invasion and evaluate its sensitivity and specificity. Results:In this study, there were 169 cases. Postoperative pathological results showed that 18 cases (10.6%) were of low grade and 151 cases (89.4%) were of high grade. There were 2 patients (1.2%) with pT a stage, 44 patients (26.0%) with pT 1 stage, 37 patients (21.9%) with pT 2 stage, 81 patients (47.9%) with pT 3 stage and 5 patients (3.0%) with pT 4 stage. According to tumor stage, 46 patients were included into non-muscle invasive disease (NMID, pT a/T is/T 1) group and 123 patients were included into muscle invasive disease (MID, pT 2/T 3/T 4) group. Univariate analysis showed that hydronephrosis ( OR=2.919, 95% CI 1.332-6.387, P=0.007) was significantly correlated with MID. Tumor location in ureter ( OR=1.898, 95% CI 0.960-3.800, P=0.067), higher NLR value ( OR=1.313, 95% CI 0.9901.832, P=0.082) and FIB concentration ( OR=1.436, 95% CI 1.008-2.125, P=0.056) might have potential association with MID. Stepwise regression method was used to screen out PLT, FIB and hydronefrosis as the optimal combination for MID prediction. multivariate analysis suggested that PLT decreasing ( OR=0.727, 95% CI 0.548-0.955, P=0.023), FIB increasing ( OR=1.629, 95% CI 1.084-2.552, P=0.025) and hydronephrosis ( OR=2.500, 95% CI 1.111-5.601, P=0.026) were independent predictors of MID.The C-index of the model constructed by the three factors was 0.682, and the P-value of the goodness of fit was 0.778. The ROC curve showed that the optimal cut-off point for the prediction of high-risk MID by the nomogram was 0.627, achieving 39.1% specificity, 88.6% sensitivity and 0.682 area under the curve (AUC). Conclusions:Preoperative decrease of PLT, increase of FIB and hydronephrosis were independent factors for predicting UTUC invading muscle.
9.Clinical and genetic features of X-linked Alport syndrome in men positive for the collagen Ⅳ α5 chain in epidermal basement membrane.
Yanqin ZHANG ; Jie DING ; Fang WANG ; Hongwen ZHANG ; Huijie XIAO ; Yong YAO ; Xuhui ZHONG ; Na GUAN ; Xiaoyu LIU ; Lixia YU ; Jingcheng LIU ; Jiyun YANG
Chinese Journal of Pediatrics 2016;54(1):61-64
OBJECTIVETo analyze the clinical and genetic features of X-linked Alport syndrome (XLAS) in men positive for the collagen α5(Ⅳ) chain in epidermal basement membrane.
METHODThis was a retrospective study. Totally 725 families were diagnosed as Alport syndrome in Department of Pediatrics of Peking University First Hospital during January 1998 to December 2014, among them 450 patients were males with XLAS. Patients who met both of the following two criteria were included in this study. (1)Patients underwent α5(Ⅳ) chain staining in the epidermal basement membrane. (2)Mutations in COL4A5 gene were detected.Mann-Whitney test and χ(2) test were used.
RESULTTotally 140 males with XLAS were included in this study, 18 cases were α5 (Ⅳ)-positive and 122 cases were α5 (Ⅳ)-negative. The two groups of patients were compared, the median age at analysis was 11.0 vs. 7.2 years (Z = -1.839, P = 0.066), the 24-hour urine protein was 1.50 vs. 0.57 g/d (Z = -1.212, P = 0.226), the rate of hearing loss was 28% vs. 53% (χ(2) = 3.619, P = 0.067), the number of patients progressed to end stage renal disease (ESRD) was 4 vs. 12 (χ(2) =2.377, P = 0.128), the median age of ESRD was 31.0 vs. 16.6 years (Z = -2.554, P = 0.011), the rate of missense mutations in COL4A5 gene was 67% vs. 52% (χ(2) = 1.424, P = 0.313).
CONCLUSIONCompared the two groups of patients with positive and negative staining for the collagen Ⅳ α5 chain in epidermal basement membrane, there was no significant difference in the proteinuria level, the rate of hearing loss and genotype of COL4A5 gene. But the patients with positive staining progressed to ESRD significantly later than the patients with negative staining.
Basement Membrane ; pathology ; Child ; Collagen Type IV ; genetics ; DNA Mutational Analysis ; Deafness ; Humans ; Kidney Failure, Chronic ; Male ; Mutation, Missense ; Nephritis, Hereditary ; genetics ; pathology ; Proteinuria ; Retrospective Studies
10.Clinical characteristies of atypical hemolytie uremic syndrome associated with H factor antibody in children.
Na GUAN ; Xiaoyu LIU ; Yong YAO ; Jiyun YANG ; Fang WANG ; Huijie XIAO ; Jie DING ; Minghui ZHAO ; Feng YU ; Fengmei WANG
Chinese Journal of Pediatrics 2014;52(3):223-226
OBJECTIVETo investigate the clinical characteristics, renal pathology, treatment and prognosis of children with atypical hemolytic uremic syndrome associated with H factor antibody.
METHODFour children less than 18 yr of age admitted from Nov. 2010 to May 2011 in Peking University First Hospital were included. They all met the criteria for atypical hemolytic uremic syndrome and with positive serum anti factor H antibody. They aged from 5 to 11 yr. Data on clinical manifestations, renal pathology, treatment and prognosis were analyzed.
RESULTAll of the 4 cases had gastrointestinal symptoms such as vomiting, abdominal pain, or abdominal distension. None of them had diarrhea. Two children had hypertension. One child had episodes of convulsion. One child had history of atypical hemolytic uremic syndrome. All of them had low serum complement C3. Three of them had low serum factor H (38.0, 88.4, 209.4 mg/L). All of them had serum antibody to factor H (1: 7 068, 1: 1 110, 1: 174, and 1: 869). Three of them received renal biopsy, all of them showed thrombotic microangiopathy. All of them were treated with steroid combined with mycophenolate mofetil. Two children received plasma exchange. They were followed up for 8 to 29 months. The renal function became normal and proteinuria relieved in all of them. The serum factor H concentration increased to 405.8, 155.8 and 438.4 mg/L, respectively. The titer of anti factor H antibody decreased to 1: 119, 1: 170, 1: 123, and 1: 674, respectively.
CONCLUSIONGastrointestinal symptom is common in children with atypical hemolytic uremic syndrome associated with H factor antibody. Hypocomplementemia was observed in all of them. Steroid combined with mycophenolate mofetil seemed to be effective for them. The monitoring of serum factor H and antibody to factor H may help diagnosis and treatment.
Atypical Hemolytic Uremic Syndrome ; Autoantibodies ; blood ; immunology ; Child ; Child, Preschool ; Complement Factor H ; immunology ; Creatinine ; blood ; Female ; Hemolytic-Uremic Syndrome ; drug therapy ; immunology ; pathology ; Humans ; Kidney ; pathology ; physiopathology ; Kidney Function Tests ; Male ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; therapeutic use ; Plasma Exchange ; Prednisolone ; administration & dosage ; therapeutic use ; Prognosis ; Retrospective Studies