Diagnostic and prognostic value of combined detection of serum Lp-PLA2,NSE and S-100β in patients with carbon monoxide poisoning complicated with acute cerebral infarction / 国际检验医学杂志

Objective To explore the value of combined detection of lipoprotein-associated phospholipase A2(Lp-PLA2),neuron specific enolase(NSE)and S-100 calcium binding protein β(S-100β)in the diagnosis and prognosis evaluation of acute cerebral infarction(ACI)in patients with carbon monoxide poisoning(CMP).Methods A total of 102 patients with CMP complicated with ACI admitted to the hospital from Jan-uary 2020 to November 2021 were selected as the study group,meanwhile,102 patients with simple CMP were enrolled as the control group.Patients in the study group were followed up for 6 months after discharge,ac-cording to the follow-up results,they were grouped into good prognosis group(60 cases)and poor prognosis group(42 cases).The serum levels of Lp-PLA2,NSE and S-100β were detected by enzyme-linked immunosor-bent assay(ELISA).The receiver operating characteristic(ROC)curve was applied to analyze the value of the combination of serum Lp-PLA2,NSE and S-100β in the early diagnosis and prognosis evaluation of patients with CMP and ACI.Results Compared with the control group,the levels of Lp-PLA2,NSE and S-100β in the study group were obviously higher(P<0.05).The ROC curve analysis results showed that the area under the curve(AUC)of the combined detection of serum Lp-PLA2、NSE、S-100β for the diagnosis of CMP complicat-ed with ACI was greater than the AUC of single detection of each indicator(P<0.001).Compared with the good prognosis group,the levels of Lp-PLA2,NSE and S-100β in the poor prognosis group were obviously higher(P<0.05).The results of ROC curve analysis showed that the AUC of the combined detection of ser-um Lp-PLA2、NSE、S-100β for the prognosis of patients with CMP complicated with ACI was greater than the AUC of single detection of each indicator(P<0.05).Conclusion The expression of Lp-PLA2,NSE and S-100β in serum of patients with CMP complicated with ACI is high,and the combined detection of the three has certain value in the diagnosis and prognosis evaluation for patients with CMP complicated with ACI.

The predictive value of t-PA,CgA,LP-PLA2 for MACE after percutaneous coronary intervention / 国际检验医学杂志

Objective To investigate the predictive value of tissue plasminogen activator(t-PA),chro-mogranin A(CgA),and lipoprotein related phospholipase A2(LP-PLA2)in serum for major adverse cardio-vascular event(MACE)after percutaneous coronary intervention(PCI).Methods A total of 120 patients with coronary heart disease who underwent PCI in the hospital from August 2020 to August 2022 were en-rolled in the study.According to whether MACE occurred within 1 year after PCI,the patients were divided into MACE group(33 cases)and non-MACE group(87 cases).The levels of serum t-PA,CgA,LP-PLA2 and clinical data were compared between the MACE group and the non-MACE group.Multivariate Logistic regres-sion was used to analyze the risk factors of MACE after PCI.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of t-PA,CgA and LP-PLA2 alone or in combination for MACE after PCI.Results The proportion of patients with smoking history,NT-proBNP,CgA,LP-PLA2,and the propor-tion of patients with hypertension in the MACE group were higher than those in the non-MACE group(P＜0.05),while left ventricular ejection fraction(LVEF)and t-PA were lower than those in the non-MACE group(P＜0.05).There were no significant differences in age,gender composition,serum creatinine,triglyc-erides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),drinking history,NYHA cardiac function classification,combined diabetes,application of aspirin,and application of clopidogrel between the two groups(P＞0.05).Multivariate Logistic regression analysis showed that smoking history,increased NT-proBNP,hypertension,decreased LVEF,decreased t-PA,increased CgA and increased LP-PLA2 were risk factors for MACE after PCI(P＜0.05).ROC curve analysis showed that the areas under the curves(AUCs)of serum t-PA,CgA and LP-PLA2 alone or in combination for predicting MACE after PCI were 0.785(95％CI:0.693-0.877),0.678(95％CI:0.564-0.791),0.730(95％CI:0.636-0.824),0.888(95％CI:0.830-0.946),respectively.The efficacy of combined prediction was bet-ter than those of single detections(P＜0.05).Conclusion The lower the serum t-PA level is and the higher the CgA and LP-PLA2 levels are,the greater the risk of MACE after PCI is.The combination of the three in-dicators has higher value in predicting MACE after PCI.

Research progress on the role of lipoprotein-associated phospholipase A2 in acute coronary syndrome / 基础医学与临床

Lipoprotein-associated phospholipase A2(Lp-PLA2)is a protein composed of 441 amino acids,which can promote the aggregation of inflammatory cells to the inflammatory response site and the release of inflammatory factors.It can promote the synthesis of matrix metalloproteinases,increase the number of foam cells and extra cel-lular matrix in atherosclerotic plaque,attenuate plaque fiber cap and prone to rupture,thus promote the onset of acute coronary syndrome(ACS).Therefore,the determination and regulation of Lp-PLA2 levels in patients with ACS are clinically significant.

Relationship between serum indexes,pathogenetic condition and prognosis in patients with acute ischemic stroke / 天津医药

Objective To discuss the relationship between serum lipoprotein-associated phospholipase A2(Lp-PLA2),low-density lipoprotein(LDL),amyloid beta 1-42(Aβ1-42)and soluble intercellular adhesion molecule-1(sICAM-1)levels,the National Institutes of Health Stroke Scale(NIHSS)score and prognosis in patients with acute ischemic stroke(AIS).Methods A total of 106 patients with AIS who underwent intravenous thrombolysis(the thrombolysis group),30 AIS patients without thrombolysis(the non-thrombolysis group)and 95 healthy individuals(the control group)were included in the study.The thrombolysis group was divided into the recanalization group(n=41)and the non-recanalization group(n=65)according to whether the vein was recanalized after thrombolysis.Patients were divided into the mild group(n=45),the moderate group(n=36)and the severe group(n=25)based on the NIHSS score.They were divided into the good prognosis group(n=65)and the poor prognosis group(n=41)based on the modified Rankin Scale(mRS)score.Serum levels of four indexes in different groups were compared.Their relationship with the NIHSS score and the prognosis was analyzed.Results The vein recanalization rate in 106 patients with thrombolysis was 38.68%(41/106).Serum Lp-PLA2,LDL,Aβ1-42 and sICAM-1 levels were lower in the recanalization group than those in the non-canalization group(P＜0.05).Serum Lp-PLA2,LDL,Aβ1-42 and sICAM-1 levels increased successively in the control group,the thrombolysis group and the non-thrombolysis group(P＜0.05).The 4 serum indexes increased with the aggravation of disease condition,and were positively correlated with NIHSS score(P＜0.05).High serum levels of Lp-PLA2,LDL,Aβ1-42 and sICAM-1 were risk factors for poor prognosis of patients with thrombolysis(P＜0.05).The area under the curve(AUC)and specificity of the combination of 4 serum indexes for predicting poor prognosis of patients with thrombolysis were higher than those of prediction with single index(P＜0.05).Conclusion The expression levels of serum Lp-PLA2,LDL,Aβ1-42 and sICAM-1 in patients with AIS are high.They can be used as important reference indexes for disease condition monitoring and prognosis evaluation.

Research Advance of Chinese Medicine in Treating Atherosclerosis: Focus on Lipoprotein-Associated Phospholipase A2 / 中国结合医学杂志

As a serious cardiovascular disease, atherosclerosis (AS) causes chronic inflammation and oxidative stress in the body and poses a threat to human health. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 (PLA2) family, and its elevated levels have been shown to contribute to AS. Lp-PLA2 is closely related to a variety of lipoproteins, and its role in promoting inflammatory responses and oxidative stress in AS is mainly achieved by hydrolyzing oxidized phosphatidylcholine (oxPC) to produce lysophosphatidylcholine (lysoPC). Moreover, macrophage apoptosis within plaque is promoted by localized Lp-PLA2 which also promotes plaque instability. This paper reviews those researches of Chinese medicine in treating AS via reducing Lp-PLA2 levels to guide future experimental studies and clinical applications related to AS.

Evaluation of 256 slice spiral CTA of coronary and serum indicators on the severity of coronary artery stenosis of patients with coronary heart disease / 中国医学装备

Objective:To explore the evaluation of 256 slice spiral computed tomography angiography(CTA)of coronary,serum lipoprotein associated phospholipase A2(Lp-PLA2)and angiopoietin like protein 3(ANGPTL3)on the severity of coronary artery stenosis of patients with coronary heart disease.Methods:A total of 102 patients with coronary heart disease who were diagnosed and treated at Hebei Chest Hospital from July 2022 to March 2023 were selected as the study subjects.According to the Gensini score about the severity of coronary artery stenosis,they were divided into mild stenosis group(0 score≤Gensini score≤20 scores),moderate stenosis group(20 scores<Gensini score≤60 scores)and severe stenosis group(Gensini score>60 scores),with 34 cases in each group.The minimum lumen diameter(MLD),percentage of area of stenosis(%AS),percentage of diameter of stenosis(%DS),minimum lumen area(MLA),Lp-PLA2 and ANGPTL3 among three groups were compared.The diagnostic efficiency of the severity of coronary artery stenosis was predicted according to receiver operating characteristic(ROC)curve.Results:The MLA and MLD values in severe stenosis group were significantly lower than those in moderate and mild stenosis groups,while%AS and%DS were significantly higher than those in moderate and mild stenosis groups(t=6.905,4.083,5.871,6.976,3.387,2.198,2.668,3.505,P<0.05),respectively.The Lp-PLA2 and ANGPTL3 values in severe stenosis group were significantly higher than those in moderate and mild stenosis groups(t=4.164,8.220,2.575,3.050,P<0.05),respectively.ROC curve analysis showed that the area under curve(AUC)values of MLA,MLD,%AS,%DS,CCTA comprehensive parameter,LpPLA2 and ANGPTL3 were respectively were 0.838,0.690,0.742,0.801,0.904,0.808 and 0.807 in predicting the severity of coronary artery stenosis.The sensitivities of them were respectively 91.20%,91.20%,64.70%,94.10%,97.10%,70.60%and 88.20%.The specificities of them were respectively 76.50%,57.40%,75.00%,50.00%,70.60%,97.10%and 70.60%.The AUC value of CCTA comprehensive parameter was respectively higher than that of LpPLA2 and ANGPTL3,but the difference was not statistically significant(P>0.05).Conclusion:256 slice spiral CCTA,serum Lp-PLA2 and ANGPTL3 have a certain efficiency in assessing the severity of coronary artery stenosis of coronary heart disease,and 256 slice spiral CCTA has higher predictive efficiency.

Effect of Jiawei Jianshen prescription on patients with spleen-kidney deficiency of idiopathic membranous nephropathy and its influence on PLA2R / 中国现代医生

@#Objective To observe the effect of Jiawei Jianshen prescription on idiopathic membranous nephropathy(IMN)with spleen-kidney deficiency and its influence on phospholipase A2 receptor(PLA2R)titer.Methods A total of 60 patients with IMN who were hospitalized or outpatients in Liuzhou Traditional Chinese Medical Hospital from January 2021 to July 2022 were selected and divided into control group and treatment group by simple random sampling method,with 30 cases in each group.The control group was given basic treatment alone,and the treatment group was given Jiawei Jianshen prescription + basic treatment.Blood urea nitrogen(BUN),serum creatinine(SCr),serum albumin(ALB),24h urinary protein quantitative and PLA2R titer were compared between two groups before and after treatment.The therapeutic effect of two groups was evaluated.Results The total effective rate of treatment group was significantly higher than that of control group(χ2=60.000,P<0.001).After treatment,the scores of edema,abdominal distension,fatigue,soreness and weakness of waist and knees in treatment group were significantly lower than those in control group(P<0.05).24h urinary protein and PLA2R titer in treatment group were significantly lower than those in control group,and ALB was significantly higher than that in control group(P<0.05).Conclusion Jiawei Jianshen prescription can significantly improve the clinical symptoms of IMN patients with spleen-kidney deficiency,increase serum ALB level,reduce 24h urinary protein quantity and PLA2R titer.

Aggressive treatment may be needed for idiopathic membranous nephropathy with focal segmental glomerulosclerosis lesions

SUMMARY OBJECTIVE: The purpose of this study was to analyze the clinical, pathological, prognostic features and treatment response of the coexistence of focal segmental glomerulosclerosis lesions with idiopathic membranous nephropathy. METHODS: This is a two-center retrospective cohort study. Patients of idiopathic membranous nephropathy were enrolled and divided into two groups with or without focal segmental glomerulosclerosis lesions according to the renal biopsy. Laboratory data and pathological manifestation were compared. Renal phospholipase A2 receptor was detected by immunofluorescence. During the follow-up, the effects of different therapies and renal function were estimated. RESULTS: A total of 236 patients were finally enrolled in this study, of which 60 and 176 idiopathic membranous nephropathy patients were enrolled in the FSGS+ and FSGS- groups, respectively. The FSGS+ group showed a higher percentage of hypertension history (38.3 vs. 20.0%, p=0.004), with a significantly higher level of systolic pressure [137 (120, 160) mmHg vs. 130 (120, 140) mmHg, p=0.009]. Main laboratory findings, including serial albumin (20.4±7.8 g/L vs. 24.5±6.7 g/L, p<0.001), 24-h proteinuria [5.61 (3.10, 7.87) g/day vs. 3.82 (2.31, 5.79) g/day, p=0.002], serial creatinine [80.8 (65.8, 97.9) μmol/L vs. 72.0 (58.7, 84.9) μmol/L, p=0.003], and estimated glomerular filtration rate [86 (66, 101) mL/min/1.73 m2 vs. 95 (81, 108) mL/min/1.73 m2, p=0.007] showed significant differences between the two groups. Pathologically, patients with focal segmental glomerulosclerosis lesions appeared with a higher percentage of crescents, a more severe degree of interstitial fibrosis, and a higher level of membranous nephropathy stage. Renal phospholipase A2 receptor showed a relatively lower positive rate of only 75.0% in the FSGS+ group in comparison with the positive rate of 90.3% in the FSGS- group (p=0.031). The prognosis was generally similar between the two groups. Among patients who were given non-immunosuppression treatment, those with focal segmental glomerulosclerosis lesions took a relatively longer period of time to achieve complete remission (29.3±7.0 m vs. 15.4±8.9 m, p=0.025) and experienced a higher rate of renal function deterioration (37.5 vs. 5.4%, p=0.033) compared with the other ones. While among those receiving immunosuppression treatment, both groups received similar remission rates. CONCLUSION: Compared with FSGS- group, idiopathic membranous nephropathy with focal segmental glomerulosclerosis lesions represented more severe nephrotic syndrome and worse renal function. In view of the renal function decline during the follow-up, more aggressive treatment with the use of immunosuppressants should be considered for idiopathic membranous nephropathy patients with focal segmental glomerulosclerosis lesions.

Actividad antiinflamatoria in vitro de Plantago major L. y Piper aduncum L. sobre la fosfolipasa A2 del veneno de la serpiente Lachesis muta muta / In vitro anti-inflammatory activity of Plantago major L. and Piper aduncum L. on phospholipase A2 from the venom of snake Lachesis muta muta

Objetivo. Evaluar la actividad inhibitoria in vitro de los extractos de Plantago major «llantén» y Piper aduncum «matico» sobre Fosfolipasa A2 (PLA2) del veneno de la serpiente Lachesis muta muta. Materiales y métodos. Esta investigación fue de tipo explicativa con diseño experimental. Se recolectaron hojas de P. major y P. aduncum en la provincia de Huarochirí en Lima, Perú. Se prepararon extractos alcohólicos diluidos en agua destilada y se realizaron los ensayos fitoquímicos, la cuantificación de fenoles y flavonoides, la cromatografía de capa fina (CCF) en celulosa y la actividad enzimática con PLA2. Se analizó la capacidad de inhibir la PLA2 con los extractos en estudio y sus fracciones. Para el análisis estadístico se utilizó la prueba de Kruskal Wallis y comparaciones múltiples de Bonferroni. Resultados. Tanto en P. major como en P. aduncum se identificó cualitativamente la presencia de fenoles, flavonoides y taninos; además, P. aduncum presentó saponinas. La inhibición de la actividad de la PLA2 del veneno por el extracto total de P. major fue del 45,3%, y sus fracciones mostraron valores de inhibición: LLF-1 con 31,1%, LLF-2 con 66,3% y LLF-3 con 65,5%. En P. aduncum, los valores de inhibición para el extracto total fueron de 86,9%, y sus fracciones presentaron inhibiciones: MF-1 con 34,3%, MF-2 con 67,1% y MF-3 con 54,9%. El análisis estadístico demostró diferencias significativas en la inhibición de la PLA2 (p=0,009) por los extractos. Conclusión. Los ensayos realizados demostraron una asociación entre el efecto antiinflamatorio de los extractos y la inhibición de la PLA2.

Objective. To evaluate the in vitro inhibitory activity of Plantago major "llantén" and Piper aduncum "matico" extracts on phospholipase A2 (PLA2) from the venom of the snake Lachesis muta muta. Materials and methods. We carried out an explanatory study with experimental design. Leaves of P. major and P. aduncum were collected in the province of Huarochirí in Lima, Peru. Then, we prepared alcoholic extracts diluted in distilled water and conducted phytochemical assays, quantification of phenols and flavonoids, thin layer chromatography (TLC) on cellulose and enzymatic activity with PLA2. The ability to inhibit PLA2 with the extracts under study and their fractions was analyzed. The Kruskal Wallis test and Bonferroni multiple comparisons were used during statistical analysis. Results. Phenols, flavonoids and tannins were qualitatively identified in both P. major and P. aduncum; in addition, P. aduncum presented saponins. The inhibition of PLA2 activity of the venom by the total extract of P. major was 45.3%, and its fractions showed the following inhibition values: 31.1% for LLF-1, 66.3% for LLF-2 and 65.5% for LLF-3. The inhibition values for the total extract of P. aduncum were 86.9%, and its fractions showed the following inhibition rates: 34.3% for MF-1, 67.1% for MF-2 and 54.9% for MF-3. Statistical analysis showed significant differences in the inhibition of PLA2 (p=0.009) by the extracts. Conclusion. The tests demonstrated an association between the anti-inflammatory effect of the extracts and PLA2 inhibition.

Utility of serum anti-phospholipase A2 receptor antibody as a biomarker in membranous nephropathy: An experience from a tertiary care center of Eastern India

Background: Membranous nephropathy (MN) is a pattern of glomerular injury. Exact categorization into primary membranous nephropathy (PMN) or secondary membranous nephropathy (SMN) is essential for treatment. An endogenous podocyte antigen, M-type phospholipase A2 receptor (PLA2R) has been discovered to be involved in the pathogenesis of PMN. Aims and Objectives: In this article, we aimed to analyze renal tissue PLA2R and serum anti-PLA2R antibodies in MN cases and determined the diagnostic utility. Materials and Methods: The study was of prospective type carried out from March 2019 to August 2020. Analysis of cases of MN was performed with PLA2R paraffin immunoflourescence and serum anti-PLA2R antibody ELISA. Results: Overall sensitivity, specificity, PPV, and NPV of serum anti-PLA2R ELISA for PMN was 91.3%, 80%, 75%, and 93.3%, respectively, and of tissue PLA2R staining for PMN was 91.67%, 81.08%, 75.86%, and 93.75%, respectively. There was strong concordance between two methods. In the patients that were followed up, we found baseline serum anti-PLA2R antibody was less in complete remission group than that in non-remission group and the reduction in serum anti-PLA2R antibody was more in complete remission group than that in non-remission group. Conclusion: Routine light and immunofluorescence examination are incapable of giving exact categorical opinion regarding PMN and SMN. Serum anti-PLA2R antibody detection and renal tissue PLA2R analysis are sensitive and specific in detecting PMN. Baseline serum anti-PLA2R antibody and anti-PLA2R antibody quantification trends are related to prognosis of PMN. So they can be incorporated as additional biomarker.

Inhibición de enzimas fosfolipasas A2 de venenos totales de serpientes como estrategia en la búsqueda de nuevos fármacos / Enzyme phospholipase A2 inhibition from snake venoms as strategy to search for new drug

Introducción: Los fármacos antiinflamatorios no esteroideos (AINEs) son ampliamente utilizados para la terapia del dolor, a pesar de sus efectos secundarios que ocurren a nivel renal, estomacal y coagulatorio. Las fosfolipasas A2 (PLA2) presentes en los venenos de serpientes, abejas e incluso en el organismo humano, son responsables de varios procesos fisiológicos y patológicos. Las enzimas hidrolizan fosfolípidos de membrana liberando ácido araquidónico, un precursor de los eicosanoides pro-inflamatorios, los cuales originan mediadores de la inflamación. Objetivo: El propósito de este trabajo es revisar nuevas moléculas capaces de bloquear la escisión de los fosfolípidos de membrana por acción de las PLA2, evitando la formación de mediadores de inflamación. Metodología: Se realizó una revisión bibliográfica de estudios publicados desde 2011 a 2021, que reportan compuestos con actividad inhibitoria frente a PLA2. El potencial de los estudios de relación estructura actividad se discute como estrategia para encontrar compuestos activos ante PLA2. Resultados: Se revisaron 26 estudios que incluyen compuestos naturales y sintéticos y se recopilaron 93 moléculas con actividad inhibitoria, destacando su potencial como inhibidores de PLA2. Conclusiones: La actividad inhibitoria de los compuestos revisados podría estar asociada a los patrones de sustitución en el anillo bencénico de las moléculas. La evaluación de características moleculares relevantes en la inhibición de PLA2 puede guiar a la identificación de candidatos para síntesis de nuevos inhibidores enzimáticos.

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain therapy, despite its side effects in renal, stomach and coagulant systems. Phospholipases A2 (PLA2) enzymes, present in snakes and bees' venoms, and even in the human organism, are responsible for several physiological and pathological processes. These enzymes hydrolyze membrane phospholipids, releasing arachidonic acid, a precursor of pro-inflammatory eicosanoids, which give rise to inflammatory mediators. Objective: The aim of the present work is to review new molecules able to block the cleavage of membrane phospholipids by the action of phospholipases A2, preventing the formation of inflammatory mediators. Methodology: A bibliographic revision from literature published from 2011 to 2021 focused on PLA2 inhibitors was carried out. The potential of structure-activity relationship studies is discussed as a strategy to find active compounds against PLA2. Results: 26 studies including natural and synthetic compounds were reviewed and data from 93 molecules with inhibitory activity were collected, highlighting its potential as PLA2 inhibitors. Conclusion: The inhibitory activity of the reviewed compounds could be associated with the substitution patterns in the benzene ring of the molecules. The evaluation of molecular moieties with relevant capacity to inhibit PLA2 will lead to the identification of candidates for synthesis of new enzymes inhibitors.

Clinical Significance of Thrombospondin Type 1 Domain-Containing 7A and Neural Epidermal Growth Factor-Like 1 Protein in M-Type Phospholipase A2 Receptor-Negative Membranous Nephropathy / 中国医学科学院学报

Objective To investigate the clinical significance of thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) in phospholipase A2 receptor (PLA2R)-negative membranous nephropathy (MN). Methods A total of 116 PLA2R-negative MN patients treated in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from 2014 to 2021 were enrolled in this study.Immunohistochemistry was employed to detect THSD7A and NELL1 in the renal tissue.The pathological characteristics,treatment,and prognosis were compared between positive and negative groups. Results The 116 PLA2R-negative MN patients included 23 THSD7A-positive patients and 9 NELL1-positive patients.One patient was tested positive for both proteins.The THSD7A-positive group showed higher positive rate of IgG4 (P=0.010),more obvious glomerular basement membrane (GBM) thickening (P=0.034),and higher proportion of stage Ⅱ MN and lower proportion of stage I MN (P=0.002) than the THSD7A-negative group.The NELL1-positive group had lower positive rates of C1q and IgG2 (P=0.029,P=0.001),less obvious GBM thickening (P<0.001),more extensive inflammatory cell infiltration (P=0.033),lower proportion of deposits on multi-locations (P=0.001),and lower proportion of atypical MN (P=0.010) than the NELL1-negative group.One patient with THSD7A-positive MN was diagnosed with colon cancer,while none of the NELL1-positive patients had malignancy.Survival analysis suggested that THSD7A-positive MN had worse composite remission (either complete remission or partial remission) of nephrotic syndrome than the negative group (P=0.016),whereas NELL1-positive MN exhibited better composite remission of nephrotic syndrome than the negative group (P=0.015).The MN patients only positive for NELL1 showed better composite remission of nephrotic syndrome than the MN patients only positive for THSD7A (P<0.001). Conclusions THSD7A- and NELL1-positive MN is more likely to be primary MN,and there is no significant malignancy indication.However,it might have a predictive value for the prognosis of MN.

Correlation between smoking and serum lipoprotein-associated phospholipase A2 level in overweight and obese men / 中南大学学报(医学版)

OBJECTIVES@#Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a vaso-specific inflammatory marker that exacerbates atherosclerotic through inflammatory responses. It can be used to predict the occurrence of adverse cardiovascular events and to assess the residual risk of cardiovascular diseases. This study aims to investigate the correlation between smoking and serum Lp-PLA2 levels in overweight and obese men, and to provide evidence for preventing the cardiovascular diseases.@*METHODS@#Male subjects, who participated in health examination at the Health Management Center, Third Xiangya Hospital, Central South University from May 1, 2020 to April 30, 2021, were selected. The smoking status and other information were collected by the Self-test Scale of Physical Examination. According to the smoking status, they were divided into a never-smoking group, a current smoking group, a quit smoking group and a passive smoking group. According to the daily smoking amount, the current smoking subjects were divided into a <10 cigarettes group, a 10 to 20 cigarettes group, a 21 to 30 cigarettes group, and a >30 cigarettes group. According to the smoking years, the current smoking subjects were divided into a <5 years group, a 5 to 10 years group, a 11 to 20 years group, and a >20 years group.Serum Lp-PLA2 levels and other clinical indexes in different smoking groups were measured and compared, the correlation between smoking and serum Lp-PLA2 levels in overweight and obese men was analyzed by logistic regression analysis.@*RESULTS@#Serum Lp-PLA2 levels were significantly different between the never-smoking group and the current smoking group (P<0.05). Logistic regression analysis showed that, before adjusting other influencing factors and in terms of smoking status, the current smoking group (OR=1.81, 95% CI 1.27 to 2.58, P<0.01) and the quit smoking group (OR=2.09, 95% CI 1.12 to 3.90, P<0.05) were positively correlated with serum Lp-PLA2 levels compared with the never-smoking group, while the passive smoking group had no correlation with serum Lp-PLA2 levels (OR=1.27, 95% CI 0.59 to 2.73, P>0.05). In terms of daily smoking amount, the 10 to 20 cigarettes group (OR=2.09, 95% CI 1.40 to 3.12, P<0.001) and the 21 to 30 cigarettes group (OR=1.98, 95% CI 1.22 to 3.20, P<0.01) were positively correlated with serum Lp-PLA2 levels compared with the never-smoking group, while the <10 cigarettes group (OR=1.45, 95% CI 0.81 to 2.60, P>0.05) and the >30 cigarettes group (OR=1.17, 95% CI 0.60 to 2.28, P>0.05) had no correlation with serum Lp-PLA2 levels. In terms of smoking years, the 5 to 10 years group (OR=1.94, 95% CI 1.07 to 3.53, P<0.05), the 11 to 20 years group (OR=2.06, 95% CI 1.33 to 3.18, P<0.01), and the >20 years group (OR=1.66, 95% CI 1.11 to 2.47, P<0.05) were positively correlated with serum Lp-PLA2 levels compared with the never-smoking group, while the <5 years group had no correlation with serum Lp-PLA2 levels (OR=1.12, 95% CI 0.38 to 3.33, P>0.05). After adjusting for age and other indicators, the correlation between smoking years and serum Lp-PLA2 levels was the same as before adjustment among the above smoking groups, except that the correlation between the smoking 5 to 10 years group and serum Lp-PLA2 levels was not significant (OR=1.77, 95% CI 0.95 to 3.29, P>0.05).@*CONCLUSIONS@#Smoking is correlated with serum Lp-PLA2 levels in overweight and obese men.

Serum lipoprotein-associated phospholipase A2 level is positively correlated with the recurrence risk of acute ischemic cerebral infarction in hypertensive patients / 南方医科大学学报

OBJECTIVE@#To explore the relationship between serum lipoprotein-associated phospholipase A2 (Lp-PLA2) level and the risk of acute ischemic stroke (AIS) recurrence in hypertensive patients.@*METHODS@#This retrospective case-control study was conducted among 211 hypertensive patients with AIS treated in Foshan First People's Hospital, including 35 patients with recurrence of AIS during the 1-year follow-up as confirmed by head CT/MR. In the overall patients, 60 had grade 1 hypertension (including 5 recurrent cases), 76 had grade 2 hypertension (with 11 recurrent cases), and 75 had grade 3 hypertension (with 19 recurrent cases). Univariate analysis, multivariate logistic regression analysis, trend analysis, and smooth curve fitting analysis were performed to explore the correlation between serum Lp-PLA2 level within 24 h after admission and the risk of AIS recurrence. The predictive efficacy of serum Lp-PLA2 level for AIS recurrence in different hypertension grades was evaluated using ROC curve analysis.@*RESULTS@#Serum Lp-PLA2 level, age, NIHSS score at admission, mRS scores at 7 days, homocysteine level and smoking status differed significantly between patients with and without AIS recurrence (P < 0.05). After adjustment for confounding factors, multivariate regression analysis showed that the highest tertile of Lp-PLA2 level was associated with a 4.13-fold increase of AIS recurrence risk compared with the lowest tertile (OR=5.13, 95% CI: 1.35-19.40), and each 1 ng/mL increase of Lp-PLA2 level was associated with a 1% increase of AIS recurrence risk (OR= 1.01, 95% CI: 1.01-1.02). Serum Lp-PLA2 level was shown to positively correlate with AIS recurrence risk, and in patients with grade 3 hypertension, its areas under the ROC curve for predicting AIS recurrence was 0.869 with a specificity of 0.893 and a sensitivity of 0.737.@*CONCLUSION@#Serum Lp-PLA2 concentration is an independent risk factor and potentially an effective predictor for AIS recurrence in patients with grade 3 hypertension.

Neuroprotective effect and mechanism of cPLA2 inhibitor increases autophagic flux on spinal cord injury / 中国骨伤

OBJECTIVE@#To investigate the mechanism of cytosolic phospholipase A2(cPLA2) inhibitor to improve neurological function after spinal cord injury (SCI).@*METHODS@#Thirty-six 3 months old female SD rats, with body mass (280±20) g, were divided into three groups (n=12):sham group, SCI group, and SCI+ arachidonyl trifluoromethyl ketone(AACOCF3) group. Balloon compression SCI model was established in all three groups. In the sham model group, the spinal cord compression model was created after the balloon was placed without pressure treatment, and the remaining two groups were pressurized with the balloon for 48 h. After successful modeling, rats in the SCI+AACOCF3 group were injected intraperitoneally with AACOCF3, a specific inhibitor of cPLA2. The remaining two groups of rats were injected intraperitoneally with saline. The animals were sacrificed in batches on 7 and 14 days after modeling, respectively. And the damaged spinal cord tissues were sampled for pathomorphological observation, to detect the expression of cPLA2 and various autophagic fluxPrelated molecules and test the recovery of motor function.@*RESULTS@#Spinal cord histomorphometry examination showed that the spinal cord tissue in the sham group was structurally intact, with normal numbers and morphology of neurons and glial cells. In the SCI group, spinal cord tissue fractures with large and prominent spinal cord cavities were seen. In the SCI+AACOCF3 group, the spinal cord tissue was more intact than in the SCI group, with more fused spinal cord cavities, more surviving neurons, and less glial cell hyperplasia. Western blot showed that the sham group had the lowest protein expression of LC3-Ⅱ, Beclin 1, p62, and cPLA2 compared with the SCI and SCI+AACOCF3 groups (P<0.05) and the highest protein expression of LC3-Ⅰ (P<0.05). P62 and cPLA2 expression in the SCI group were higher than in the SCI+AACOCF3 group (P<0.05). Behavioral observations showed that the time corresponding to BBB exercise scores was significantly lower in both the SCI and SCI+AACOCF3 groups than in the sham group (P<0.05). Scores at 3, 7, and 14 days after pressurization were higher in the SCI+AACOCF3 group than in the SCI group (P<0.05).@*CONCLUSION@#cPLA2 inhibitors can reduce neuronal damage secondary to SCI, promote neurological recovery and improve motor function by improving lysosomal membrane permeability and regulating autophagic flux.

Lipoprotein-associated phospholipase A2 combined with D-dimer to fibrinogen ratio to construct a prognostic nomogram model for patients with acute myocardial infarction after percutaneous coronary intervention / 中国医师进修杂志

Objective:To construct acute ST-segment elevation myocardial infarction (STEMI) percutaneous coronary intervention (PCI) by using lipoprotein-associated phospholipase A2 (Lp-PLA2) and D-dimer to fibrinogen ratio (D/F) and other indicators postoperative patient prognosis nomogram model and evaluation of its predictive value.Methods:A total of 291 acute STEMI patients admitted to the BenQ Hospital Affiliated to Nanjing Medical University from January 2017 to January 2020 were retrospectively selected, including but not limited to Lp-PLA2 and D/F, were collected. Receiver operating characteristic (ROC) curve and multivariate Logistic regression were used to analyze the risk factors of death within 90 d after PCI in STEMI patients, and Kaplan-Meier survival curves were drawn to compare the survival of patients in different Lp-PLA2 and D/F groups. The R language software was used to build nomogram model and decision curve.Results:The AUCs of LpPLA2 and D/F for predicting the risk of death from cardiac causes at 90 s after PCI in patients with acute STEMI were 0.896 (95% CI 0.850 to 0.932) and 0.884 (95% CI 0.837 to 0.922), respectively. The values were 59.50 μg/L and 0.46 respectively ( P<0.05); the mortality rates of acute STEMI patients in LpPLA2>59.50 μg/L and D/F>0.46 groups after PCI were higher than those in LpPLA2≤59.50 μg/L group and D/F≤0.46 group ( P<0.05); age (>66 years), left ventricular ejection fraction (LVEF) (≤45%), LpPLA2 (>59.50 μg/L), D/F (>0.46), N-terminal brain natriuretic peptide precursor (>1.55 μg/L) and fasting blood glucose (>7.00 mmol/L) were the risk of death from cardiac causes at 90 d after PCI in patients with acute STEMI ( P<0.05); when the risk thresholds were >0.24, the nomogram model could provide significant additional net clinical benefit. Conclusions:Lp-PLA2 and D/F are closely related to the prognosis of patients with acute STEMI after PCI, and the nomogram model constructed in combination with other clinical indicators can effectively predict the risk of death within 90 d after PCI.

Three cases of obinutuzumab treatment for rituximab-resistant phospholipase A 2 receptor- associated membranous nephropathy / 中华肾脏病杂志

Rituximab is currently used as a first-line therapy for phospholipase A 2 receptor-associated membranous nephropathy due to its good efficacy and safety. Although the remission rate after rituximab treatment is more than 60%, nearly 40% patients still do not respond to treatment. We used obinutuzumab to treat 3 cases of rituximab resistant PLA 2R-associated membranous nephropathy. After the first dose of 1 000 mg with or without additional dose, the amount of anti-PLA 2R antibody and urinary protein decreased significantly and the adverse reactions were mild. The results show that obinutuzumab has a certain therapeutic effect on rituximab resistant PLA 2R-associated membranous nephropathy, but the time of follow-up observation is short and can only be used as individual cases, which needs to be confirmed by a large sample and high-quality prospective cohort study.

Predictive value of lipoprotein-associated phospholipase A2 combine with systemic immune-inflammation index for coronary heart disease risk in patients with type 2 diabetes mellitus / 中国医师进修杂志

Objective:To explore the predictive value of lipoprotein-associated phospholipase A2 (Lp-PLA2) combined with systemic immune-inflammation index (SII) for coronary heart disease risk in patients with type 2 diabetes mellitus.Methods:A prospective study was performed, 130 patients with type 2 diabetes mellitus from May 2018 to May 2021 in the People′s Hospital of Pengzhou were selected. All patients underwent coronary angiography examination, and 49 cases were complicated with coronary heart disease (coronary heart disease group), 81 cases were not complicated with coronary heart disease (non-coronary heart disease group). The clinical data were recorded; the white blood cell, monocyte, platelet, neutrophils, lymphocyte, hemoglobin, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose, C-reactive protein (CRP), glycated hemoglobin and Lp-PLA2 were detected; and the SII was calculated. Multivariate Logistic regression analysis was used to analyze the independent risk factors of coronary heart disease in patients with type 2 diabetes mellitus; the efficacy of Lp-PLA2 and SII in predicting the coronary heart disease in patients with type 2 diabetes mellitus was evaluated using the receiver operating characteristics (ROC) curve.Results:There were no statistical differences in white blood cell, hemoglobin, TC, TG, LDL-C, fasting blood glucose, glycated hemoglobin and CRP between two groups ( P>0.05); the monocyte, platelet, neutrophils, Lp-PLA2 and SII in coronary heart disease group were significantly higher than those in the non-coronary heart disease group: (0.55 ± 0.22) × 10 9/L vs. (0.40 ± 0.11) × 10 9/L, (227.84 ± 40.76) × 10 9/L vs. (205.81 ± 39.04) × 10 9/L, (6.78 ± 1.45) × 10 9/L vs. (6.30 ± 1.18) × 10 9/L, (240.67 ± 41.48) μg/L vs. (214.83 ± 36.35) μg/L and 1 245.76 ± 383.08 vs. 929.84 ± 260.27, the lymphocyte and HDL-C were significantly lower than those in the non-coronary heart disease group: (1.26 ± 0.17) × 10 9/L vs. (1.41 ± 0.19) × 10 9/L and (1.15 ± 0.14) mmol/L vs. (1.23 ± 0.21) mmol/L, and there were statistical differences ( P<0.01 or <0.05). Multivariate Logistic regression analysis result showed that monocyte, HDL-C, Lp-PLA2 and SII were the independent risk factors of coronary heart disease in patients with type 2 diabetes mellitus ( OR = 1.812, 1.013, 1.013 and 2.004; 95% CI 4.430 to 6.801, 0.992 to 1.013, 1.001 to 1.026 and 0.004 to 0.855; P<0.01 ore <0.05). ROC curve analysis result showed that the area under the curve of Lp-PLA2 combined with SII to predict the coronary heart disease in patients with type 2 diabetes mellitus was significantly larger than Lp-PLA2 and SII alone: 0.783 (95% CI 0.702 to 0.851) vs. 0.681 (95% CI 0.593 to 0.760) and 0.744 (95% CI 0.660 to 0.816), and there was statistical difference ( P<0.05). Conclusions:Lp-PLA2 and SII are independent risk factors for coronary heart disease in patients with type 2 diabetes mellitus, and their combined detection can improve the predictive value of coronary heart disease.

Assessment of the feasibility of using positive anti-M-type phospholipase A 2receptor antibody detection as a noninvasive diagnostic tool for idiopathic membranous nephropathy in elderly Chinese patients / 中华老年医学杂志

Objective:To evaluate the feasibility of using positive anti-M-type phospholipase A 2 receptor(PLA 2R)antibody detection as a surrogate for renal biopsy in the diagnosis of idiopathic membranous nephropathy(IMN)in elderly Chinese. Methods:From June 2021 to March 2022, clinicopathological data of ninety-six elderly patients(≥60 years old)with positive anti-PLA 2R antibody detection(ELISA≥14 RU/ml), complete renal pathology records, and the exclusion of secondary disease and diabetes mellitus were collected from the Department of Nephrology, The First Affiliated Hospital of Zhengzhou University.Patients were divided into high eGFR group(≥60 ml·min -1·1.73 m -2)and low eGFR group(<60 ml·min -1·1.73 m -2), and the data were analyzed retrospectively. Results:Of the 96 patients, 95(99.0%)had IMN(1 in stage Ⅰ, 59 in stage Ⅱ, 34 in stage Ⅲ, and 1 in stage Ⅳ), and 1(1.0%)had atypical membranous nephropathy(AMN).For the IMN patients, 81(85.3%)had high eGFR and most IMN patients(66.7%)were in stage Ⅱ, with 10(12.3%)showing additional pathological findings, including mild mesangial proliferative IgA nephropathy(2 cases)and subacute tubulointerstitial nephropathy(2 cases).There were 14 patients(14.7%)with low eGFR, and most of them(57.1%)had stage Ⅲ IMN, with 10(71.4%)showing additional pathological findings.This percentage was higher than that in the high eGFR group( χ2=21.642, P<0.05).The most common additional pathological findings were acute tubular injury(4 cases)and ischemic kidney injury(2 cases). Conclusions:Positive anti-PLA 2R antibody detection is highly predictive of IMN in elderly Chinese patients, but it often co-exists with other pathological entities.The advantages of renal biopsy in detecting other pathological conditions and the risks associated with the procedure should be evaluated.

Correlation between serum anti-phospholipase A2 receptor antibody combined with glomerular complement C3 deposition and clinicopathology and prognosis in patients with idiopathic membranous nephropathy / 中华肾脏病杂志

Objective:To investigate the correlation between serum anti-phospholipase A2 receptor antibody (SAb) combined with glomerular complement C3 (GC3) deposition and clinicopathologic features and prognosis in patients with idiopathic membranous nephropathy (IMN).Methods:It was a retrospective cohort study. The patients diagnosed with IMN in Affiliated Hospital of Qingdao University from July 1, 2019 to April 30, 2022 were enrolled, and the clinical and pathological data were collected and analyzed. The patients were divided into negative SAb and negative GC3 (SAb -/GC3 -) group, negative SAb and positive GC3 (SAb -/GC3 +) group, positive SAb and negative GC3 (SAb +/GC3 -) group and positive SAb and positive GC3 (SAb +/GC3 +) group according to the status of SAb titer and GC3 deposition. Clinical and pathological characteristics among the groups were compared. Kaplan-Meier survival curve was used to compare the cumulative renal remission rates of different groups. Cox regression analysis model was used to analyze the related factors of renal remission. Results:A total of 143 IMN patients aged (53.35±12.34) years old were included in the study, including 94 males (65.7%). There were 17 patients (11.9%) in the SAb -/GC3 - group, 30 patients (21.0%) in the SAb -/GC3 + group, 19 patients (13.3%) in the SAb +/GC3 - group, and 77 patients (53.8%) in the SAb +/GC3 + group. Compared with SAb -/GC3 - group, the level of serum albumin was lower in the SAb +/GC3 + group, and the level of 24 h urine protein, SAb titer, and the proportions of glomerular anti-phospholipase A2 receptor antigen and renal tubule atrophy were higher in the SAb +/GC3 + group (all P<0.05). After 26.0 (19.0, 36.0) months of follow-up, a total of 96 patients (67.1%) attained remission. The proportion of patients receiving immunosuppressive therapy in the SAb +/GC3 + group was higher than that in the SAb -/GC3 - group [93.5% (72/77) vs. 70.6% (12/17), fisher value=8.974, P=0.016] and the proportion of renal remission rate in the SAb +/GC3 + group was lower than that in the SAb -/GC3 - group [49.4% (38/77) vs. 100% (17/17), χ2=25.438, P<0.001]. Kaplan-Meier survival curve result showed that the cumulative renal remission rate in the SAb +/GC3 + group was significantly lower than that in the SAb -/GC3 - group (Log-rank χ2=31.538, P<0.01). Multivariate Cox regression analysis result showed that 24 h urine protein level ( HR=0.891, 95% CI 0.803-0.988, P=0.029), SAb titer ( HR=0.996, 95% CI 0.992-1.000, P=0.042) and SAb +/GC3 + (with SAb -/GC3 - group as reference, HR=0.414, 95% CI 0.204-0.827, P=0.013) were independent related factors for renal remission in patients with IMN. Conclusions:IMN patients with positive SAb and GC3 deposition have more severe clinical and pathological changes, lower renal cumulative remission rates, and are more likely to have poor prognosis. The combined assessment of SAb and GC3 deposition may be helpful for evaluating prognosis and guiding treatment in IMN patients.