1.Clinical value of systemic vascular resistance index combined with procalcitonin in the early diagnosis of sepsis
Tingqiu WEI ; Shuwang WEI ; Hongkun HUANG ; Yuxiu WEI ; Lingling XIE ; Zhanhong TANG ; Jieyan LAN ; Zhangxu WEI
Chinese Critical Care Medicine 2016;28(10):921-926
Objective To assess the clinical value of systemic vascular resistance index (SVRI) combined with serum procalcitonin (PCT) and sequential organ failure assessment (SOFA) score in the early diagnosis of sepsis. Methods A retrospective study was conducted. The data of critical patients admitted to Department of Critical Care Medicine of the Third People's Hospital of Hechi from November 2013 to April 2016 were enrolled. The clinical data were recorded as follows: gender, age, infection site, SOFA score, serum PCT level (enzyme linked fluorescence analysis) within 1 hour after intensive care unit (ICU) admission, hemodynamics parameters, including mean arterial pressure (MAP), central venous pressure (CVP), cardiac index (CI), SVRI, global end diastolic volume index (GEDVI), extravascular lung water index (EVLWI), which were monitored by pulse indicator continuous cardiac output (PiCCO) after ICU admission. The patients were divided into sepsis and non-sepsis groups according to the diagnostic criteria of sepsis. Septic patients were divided into low SVRI group, normal SVRI group, and high SVRI group according to SVRI normal value (170-240 kPa·s·L-1·m-2), and the differences in parameters among the three groups were compared. The correlations between SVRI and various parameters were analyzed by using Pearson correlation analysis. The receiver operating characteristic curve (ROC) was plotted to evaluate the diagnostic efficiency of each parameter. Results Totally 103 critical patients were enrolled, 55 in sepsis group, and 48 in non-sepsis group. Compared with non-sepsis group, SVRI in septic group was significantly lowered (kPa·s·L-1·m-2: 146.56±45.17 vs. 188.04±56.27), and serum PCT was significantly increased (μg/L: 10.43±6.17比0.32±0.11) with statistically significant differences (both P < 0.05). In 55 sepsis patients, there were 21 in low SVRI group, 19 in normal SVRI group, and 15 in high SVRI group. There were no statistically significant differences in gender, age and infection site among the three groups, indicating that the baseline data among all groups was balanced with comparability. SOFA score, PCT, and CI in the low SVRI group were significantly higher than those of normal SVRI and high SVRI groups [SOFA: 10.57±2.89 vs. 5.73±2.28, 5.73±2.15, PCT (μg/L): 24.15±12.43 vs. 7.18±5.05, 7.39±4.38, CI (mL·s-1·m-2): 71.01±9.67 vs. 62.01±8.34, 62.51±8.67, all P < 0.05], but no significant difference was found between the normal SVRI group and high SVRI group. There was no statistically significant difference in MAP, CVP, EVLWI, and GEDVI among the three groups. It was shown by Pearson correlation analysis that SVRI was negatively correlated with PCT, SOFA score, and CI (r value was -0.622, -0.598, -0.398, all P = 0.000). It was shown by ROC curve that area under ROC curve (AUC) of PCT combined with SVRI for diagnosis of sepsis was higher than that of PCT or SVRI alone (0.943 vs. 0.911, 0.884). When the cut-off value of PCT was 3.79 μg/L, and cut-off value of SVRI was 156.81 kPa·s·L-1·m-2, the sensitivity and specificity were 94.6% and 92.3% respectively. Conclusions For sepsis patients, SVRI is related to PCT and SOFA score. Combined monitoring of PCT, SVRI, SOFA score can accurately reflect the severity of sepsis patients, guide diagnosis and treatment, and estimate prognosis. The efficacy of PCT combined with SVRI in the early diagnosis of sepsis is better than that of the two alone.
2.Overexpression of PTEN Inhibits Renal Epithelial-mesenchymal Trans-differentiation Induced by TGF-β1
Honglan WEI ; Rui ZENG ; Lin LIU ; Juan ZHANG ; Jun LUO ; Shuwang GE ; Gang XU
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2009;38(6):721-724
Objective To investigate the inhibitory effects of overexpression of PTEN on renal epithelial-mesenchymal trans-differentiation induced by TGF-β1,and the signaling transduction mechanism.Methods HKC cells were transfected with GFP-PTEN via lipofectAMINE2000.The efficiency of transfection was detected by fluorescence microscope.The expression of PTEN protein and mRNA in the translected cells was detected by Western blot and RT-PCR respectively.The experiment was divided into four groups:normal group,TGF-β1 stimulation group,GFP-PTEN+TGF-β1 group and empty vector+TGF-β1 group.The expression of E-cadherin,a-SMA,Akt and p-Akt was detected by Western blot.Results Most ceils transfected with GFP-PTEN expressed GFP.The expression of PTEN protein and mRNA was strongly increased when HKC cells were transfected with GFP-PTEN(all P<0.05).In both TGF-β1 stimulation group and empty vector+TGF-β1 group,the expression level of E-cadherin was lower(all P<0.05),while that of p-Akt and a-SMA was higher than in normal group(both P<0.05).The expression level of p-Akt and a-SMA in GFP-PTEN+TGF-β1 group was Iower(both P<0.05),while that of E-cadherin was higher than in TGF-β1 stimulation group and empty vector+TGF-β1 group(both P<0.05).The expression of Akt was similar in the four groups.Conclusion Overexpression of PTEN can inhibit renal epithelial-mesenehymal trans-differentiation induced by TGF-β1 through suppressing the activation of PI3K/Akt signal pathway.
3.Upregulated DJ-1 promotes renal tubular EMT by suppressing cytoplasmic PTEN expression and Akt activation.
Ying, YAO ; Honglan, WEI ; Lili, LIU ; Lin, LIU ; Shoujun, BAI ; Caixia, LI ; Yun, LUO ; Rui, ZENG ; Min, HAN ; Shuwang, GE ; Gang, XU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2011;31(4):469-75
Recently, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is suggested as a new agent in the fighting against fibrogenesis. In tumor, DJ-1 is identified as a negative regulator of PTEN. But the expression of DJ-1 and the regulation of PTEN in fibrosis are unclear. Renal fibrosis was induced in 5/6 subtotal nephrectomy rat model. Human proximal tubular epithelial cells (HKC) were treated with transforming growth factor-beta 1 (TGF-β1), or transfected with DJ-1 or PTEN. Confocal microscope was used to investigate the localization of DJ-1 and PTEN. The selective phosphoinositide-3 kinase (PI3K) inhibitor, LY294002, was administered to inhibit PI3K pathway. The DJ-1 and PTEN expression, markers of epithelial-mesenchymal transition (EMT) and Akt phosphorylation were measured by RT-PCR, Western blotting or immunocytochemistry. In vitro, after HKC cells were stimulated with 10 ng/mL TGF-β1 for 72 h, the expression of DJ-1 was increased, and that of PTEN was decreased. In vivo, the same results were identified in 5/6-nephrectomized rats. In normal HKC cells, most of DJ-1 protein localized in cytoplasm, and little in nucleus. TGF-β1 upregulated DJ-1 expression in both cytoplasma and nuclei. In contrary, TGF-β1 emptied cytoplasmic PTEN protein into nucleus. Overexpression of DJ-1 decreased the expression of PTEN, promoted the activation of Akt and the expression of vimentin, and also led to the loss of cytoplasmic PTEN. Contrarily, overexpression of PTEN protected HKC cells from TGF-β1-induced EMT. In conclusion, DJ-1 is upregulated in renal fibrosis and DJ-1 mediates EMT by suppressing cytoplasmic PTEN expression and Akt activation.
4.Synthesis of related substances of tebipenem pivoxil
Wei GUO ; Chunwen XIE ; Wensheng WANG ; Deqiang ZHENG ; Shuwang HE
Journal of China Pharmaceutical University 2018;49(3):286-290
To enhance the quality control of tebipenem pivoxil and establish its quality criteria,the synthetic route of tebipenem pivoxil was analyzed and five related substances (P1,P2,P6,P8 and P9)were synthesized and characterized by 1H NMR and MS.The purities of the related substances were over 95% via HPLC detec-tion.The target compounds can be used as the reference of the related substances in the quality control of tebi-penem pivoxil.The starting materials were cheap and easy to obtain;the reaction conditions were mild.
5.Upregulated DJ-1 Promotes Renal Tubular EMT by Suppressing Cytoplasmic PTEN Expression and Akt Activation
YAO YING ; WEI HONGLAN ; LIU LILI ; LIU LIN ; BAI SHOUJUN ; LI CAIXIA ; LUO YUN ; ZENG RUI ; HAN MIN ; GE SHUWANG ; XU GANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2011;31(4):469-475
Recently,phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is suggested as a new agent in the fighting against fibrogenesis.In tumor,DJ-1 is identified as a negative regulator of PTEN.But the expression of DJ-1 and the regulation of PTEN in fibrosis are unclear.Renal fibrosis was induced in 5/6 subtotal nephrectomy rat model.Human proximal tubular epithelial cells (HKC) were treated with transforming growth factor-beta 1 (TGF-β1),or transfected with DJ-1 or PTEN.Confocal microscope was used to investigate the localization of DJ-1 and PTEN.The selective phosphoinositide-3 kinase (PI3K) inhibitor,LY294002,was administered to inhibit PI3K pathway.The DJ-1 and PTEN expression,markers of epithelial-mesenchymal transition (EMT) and Akt phosphorylation were measured by RT-PCR,Western blotting or immunocytochemistry.In vitro,after HKC cells were stimulated with 10 ng/mL TGF-β1 for 72 h,the expression of DJ-1 was increased,and that of PTEN was decreased.In vivo,the same results were identified in 5/6-nephrectomized rats.In normal HKC cells,most of DJ-1 protein localized in cytoplasm,and little in nucleus.TGF-β1 upregulated DJ-1 expression in both cytoplasma and nuclei.In contrary,TGF-β1 emptied cytoplasmic PTEN protein into nucleus.Overexpression of D J-1 decreased the expression of PTEN,promoted the activation of Akt and the expression of vimentin,and also led to the loss of cytoplasmic PTEN.Contrarily,overexpression of PTEN protected HKC cells from TGF-β1-induced EMT.In conclusion,DJ-1 is upregulated in renal fibrosis and DJ-1 mediates EMT by suppressing cytoplasmic PTEN expression and Akt activation.
6.The significance of serum phospholipase A2 receptor antibody in remission of idiopathic membranous nephropathy
Xiaoxin CHU ; Xiu XU ; Xiaofeng HE ; Min HAN ; Jufang SHAO ; Yueqiang LI ; Wei DAI ; Gang XU ; Shuwang GE
Chinese Journal of Nephrology 2018;34(10):752-758
Objective To identify the significance of serum phospholipase A2 receptor antibody (PLA2R-Ab) in idiopathic membranous nephropathy (IMN) patients.Methods A total of 108 patients diagnosed as IMN by medical history,physical examination,laboratory examination and renal biopsy in Tongji Hospital affiliated to Tongji Medical College,Huazhong University of Science and Technology between Dec 1,2014 and Aug 31,2017 were enrolled,and all related data were recorded.According to the results of serum PLA2R-Ab test,patients were divided to positive group and negative group,and the data were compared with the independent sample t test and the chi-square test.Kaplan-Meier survival analysis was performed to compare remission rates between groups,and the Logrank method was used to evaluate the significance of differences.Univariate and multivariate Cox regression analysis were used to verify predicting factors for achieving remission.Results Overall,67.6%(73/108) patients had detectable serum PLA2R-Ab.Compared with patients in negative group,patients in positive group exhibited higher proportion of male patients (P=0.002),lower level of serum albumin (P < 0.001),higher level of cholesterol (P < 0.001),lower level of immunoglobulin G (P <0.001),higher level of proteinuria (P=0.003),a lower of chance of remission (P=0.049),longer time needed to achieve partial remission (P=0.001) and complete remission (P=0.002).The 1-and 2-year cumulative renal partial remission rates were 72.4%,86.1%,and the cumulative renal complete remission rates were 43.8%,54.0%,respectively.Patients in negative group had higher partial remission (x2=9.84,P=0.002) and complete remission (x2=15.50,P<0.001) than those in positive group.Multivariate Cox regression model indicated that serum positive PLA2R-Ab was a significant independent risk factor.Conclusions IMN patients with serum PLA2R-Ab show more severe condition and lower remission rates than those without serum PLA2R-Ab.Serum positive PLA2R-Ab is an independent remission-related predictor for IMN patients.
7.Role of Protein Kinase Cin Advanced Glycation End Products-induced Epithelial-Mesenchymal Transition in Renal Proximal Tubular Epithelial Cells
GE SHUWANG ; ZENG RUI ; LUO YUN ; LIU LIN ; WEI HONGLAN ; ZHANG JUAN ; ZHOU HUAN ; XU GANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2009;29(3):281-285
d by AGE-BSA may be mediated via the activation of PKC signal transduction pathway.
8.Risk factors for secondary infection in the treatment with anti-neutrophil cytoplasmic antibody-associated vasculitis
Jiao BAO ; Yichun CHENG ; Jufang SHAO ; Wei DAI ; Yueqiang LI ; Xiaofeng HE ; Min HAN ; Shuwang GE ; Gang XU
Chinese Journal of Nephrology 2019;35(5):351-358
Objective To investigate the clinical characteristics and risk factors of secondary infection in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV).Methods One hundred and eighteen patients newly diagnosed with AAV at the institute of nephrology,Tongji hospital affiliated to Huazhong university of science and technology,from 2012 to 2017,were analyzed retrospectively.Induction therapy included single corticosteroids,combination of corticosteroids with cyclophosphamide and combination of corticosteroids with other immunosuppressive agents.End point was defined as moderate to severe infection which was diagnosed by the clinical and radiological manifestation as well as microbiological evidences.The infection-related survival curve was drawn to reflect the time when the infection occurred.The clinical baseline variables in patients with and without infection were compared.Multivariate Logistic regression model was used to determine the independent predictors of infection.Receiver-operating characteristic curve (ROC) was plotted for evaluating the predictive value of lymphocyte on moderate to severe infection.Results During followup of median 3 months (1-30 months),88 infection episodes were found in 63 (53.4%) patients,of which 54 times (61.4%) occurred within 6 months after treatment,46 times (52.3%) happened within 3 months after treatment.The most common organ of infection was lung (62.5%),and the most common pathogen was bacteria (51.1%).Multivariate Logistic regression model showed that lung involvement (OR=4.44,95% CI 1.59-12.41),moderate reduction of lymphocyte in follow-up (OR=5.69,95% CI 2.05-15.85) and severe lymphocyte reduction (OR=36.28,95%CI 3.45-381.17) were independent risk factors of secondary infection in AAV patients (all P < 0.05).ROC curve showed that the area under the curve of lymphocyte as a predictor of severe infection was 0.767 (95% CI 0.64-0.89,P < 0.05).Based on lymphocyte less than 0.49× 109/L which was the cut-off value for predicting severe infection,the sensitivity and the specificity were 83.9% and 71.9%,respectively.Conclusions Lung involvement and moderate-severe lymphopenia during follow-up are independent risk factors of secondary infection in AAV patients.Hence,physician should pay more attention to those patients,and adjust treatment in time to avoid the occurrence of infection.
9.The evaluation of structural remodeling of the left atrium in elderly patients with non-valvular atrial fibrillation
Lei LI ; Ya BIAN ; Shuwang LIU ; Yuan ZHANG ; Renji WANG ; Haiyi YU ; Xinheng FENG ; Zhaoping LI ; Wei GAO ; Ming CUI
Chinese Journal of Geriatrics 2017;36(11):1167-1170
Objective To assess the difference in left atrial properties between elderly and younger control subjects and the role of left atrium remodeling in patients of different ages with atrial fibrillation.Methods A total of 194 patients with non-valvular atrial fibrillation were enrolled from September 2014 to June 2016.Based on age,patients were divided into an elderly group (≥60 years,n=129) and a younger group (<60 years,n=65).We evaluated remodeling parameters for the left atrium using an Ultrasound Cardiography (UCG) system in 125 elder subjects,together with 64 control subjects.All remodeling parameters were recorded,including left atrial diameter (LAD),left atrial square (LAS),left atrial pressure (LAP) and left ventricular end-diastolic dimension (LVEDD).Results The elderly group had more female patients and more patients with persistent atrial fibrillation.Meanwhile,scores of CHA2DS2Vsc and levels of N-terminal pro-brain natriuretic peptide (NT-ProBNP) were significantly increased in elderly patients (both P<0.05).Moreover,the elderly group was associated with increased values of LAD and LAS[(39.1±4.4)mm vs.(37.1±5.3)mm,P<0.01;and(23.3±4.5)cm2 vs.(21.4±4.8)cm2,P<0.01;respectively],compared with those in the control group.Spearman's correlation analysis showed that LAD,LAS and LAP were all markedly related to age (r=0.213,P<0.05;r=-0.175,P<0.05;r=0.170,P<0.05;respectively),persistent onset of atrial fibrillation (r=0.401,P<0.05;r=0.446,P<0.05;r=0.160,P<0.05;respectively),and impaired heart function,measured by left ventricular ejection fraction (r=-0.4371,P<0.05;r=-0.403,P<0.05;r=-0.364,P<0.05;respectively) and NT-ProBNP (r=0.485,P<0.01;r=0.483,P< 0.01;r =0.293,P< 0.01;respectively).Conclusions Left atrial remodeling properties measured by the UCG system in the elderly with non-valvular atrial fibrillation are more serious than those in mid-aged and young subjects.As a convenient and accurate assessment of remodeling parameters,the UCG system is an excellent option for measuring left atrial remodeling in the elderly population.
10.Different levels and clinical significance of growth differentiation factor-15 in patients with atrial fibrillation
Ying WEI ; Ming CUI ; Shuwang LIU ; Haiyi YU ; Wei GAO ; Lei LI
Journal of Peking University(Health Sciences) 2024;56(4):715-721
Objective:To measure the concentration of growth differentiation factor-15(GDF-15)in the serum of patients with atrial fibrillation(AF),to study the correlations between the levels of GDF-15 and different factors including basic clinical information,biochemical examinations,and atrial structure,and further to explore the association between GDF-15 and AF types and structural remodeling.Methods:AF patients who were admitted to the ward of the Department of Cardiology at Peking Universi-ty Third Hospital between October 2017 and October 2019 were prospectively enrolled.Patients admitted to the ward at the same time with sinus rhythm and no prior AF history were enrolled in the control group.Clinical information and blood samples of the patients were collected.Enzyme-linked immunosorbent as-say was used to measure the concentration of GDF-15.SPSS 23.0 was used for statistical analysis.Results:In the study,156 AF patients(64 persistent AF and 92 paroxysmal AF)and 38 patients of the control group were included.Serum GDF-15 levels in the AF group were significantly higher than in the control group[1 112(723,1 525)ng/L vs.697(499,825)ng/L,P<0.001].Serum GDF-15 levels in the persistent AF group were significantly higher than in the paroxysmal AF group[1 140(858,1 708)ng/L vs.1 090(662,1 374)ng/L,P=0.047].The area under the curve(AUC)of serum GDF-15 levels for prediction of AF was 0.736(95%CI:0.651-0.822,P<0.001).The cut-off value was 843.2 ng/L with a sensitivity of 68.2%and a specificity of 78.9%.The AUC of serum GDF-15 levels for prediction of persistent AF was 0.594(95%CI:0.504-0.684,P=0.047).The cut-off va-lue was 771.5 ng/L with a sensitivity of 82.8%and a specificity of 35.9%.Spearman rank correlation analysis showed that the serum GDF-15 levels were positively correlated with age(r=0.480,P<0.001),left atrial pressure(LAP,r=0.300,P<0.001),and also negatively correlated with left atrial appendage flow velocity(LAAV,r=-0.252,P=0.002).Multiple linear regression analysis showed that age and LAP affected the GDF-15 levels significantly(P<0.05).Logistic regression analysis sug-gested GDF-15(OR=1.002,95%CI:1.001-1.003,P=0.004)and left atrial diameter(LAD,OR=1.400,95%CI:1.214-1.616,P<0.001)were independent predictors of AF.Conclusion:Serum GDF-15 levels are higher in AF patients.Meanwhile,serum GDF-15 levels are higher in persistent AF patients than paroxysmal AF patients.GDF-15 is associated with AF and atrial structural remodeling.