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Abstract Introduction: Sticky platelet syndrome (SPS) is a prothrombotic condition characterized by increased platelet aggregation that causes arterial and venous thrombosis. Its diagnosis is reached by identifying increased aggregation using low concentrations of adenosine diphosphate and epinephrine in platelet aggregation tests. Objectives: To identify common mutations through exome sequencing in two patients from the same family diagnosed with SPS and, thus, contribute to the molecular study of this disease. Materials and methods: Descriptive study. In January 2018, exome sequencing was performed in a 10-year-old patient treated at Fundación HOMI (Bogotá D.C., Colombia), index case, and in one of his adult first-degree relatives, both with a history of thrombotic disease and diagnosed with SPS. Exome sequencing was performed at the Complexo Hospitalario Universitario de Santiago de Compostela (Spain) using the SureSelect Clinical Research Exome V2 software by Agilent. Results: Exome sequencing led to detect genetic variants in both cases when compared with the reference sequence. The following variant was identified in the two samples: a cytosine to thymine transition at position c.236 (NM_000174.4) of the glycoprotein (GP)Ib-IX-V complex platelet membrane receptor, which causes a heterozygous transition of the amino acid threonine to isoleucine (i.e., a transition from hydrophilic amino acid to a hydrophobic amino acid) at position p. 79 of the extracellular leucine-rich repeat domain of GPIba subunit of the (GP)Ib-IX complex, involving a conformational change of the main receptor of ligands IB alpha, which might result in platelet hyperaggregation and thrombosis. This variant has not been described in patients with SPS to date. Conclusion: The mutation identified in both samples could be related to SPS considering the importance of glycoprotein IX in platelet function.
Resumen Introducción. El síndrome de plaqueta pegajosa (SPP) es una condición protrombótica caracterizada por un incremento de la agregabilidad plaquetaria que causa trombosis arterial y venosa. Su diagnóstico se realiza al identificar el aumento de la agregabilidad utilizando bajas concentraciones de adenosín difosfato y epinefrina en pruebas de agregación plaquetaria. Objetivos. Identificar mutaciones comunes mediante secuenciación del exoma en dos pacientes de una misma familia con diagnóstico de SPP y, de esta forma, contribuir al estudio molecular de esta enfermedad. Materiales y métodos. Estudio descriptivo en el que se realizó secuenciación del exoma en un paciente de 10 años atendido en la Fundación HOMI (Bogotá, Colombia), caso índice, y en uno de sus familiares adultos en primer grado, ambos con antecedente de enfermedad trombótica y diagnosticados con SPP. La secuenciación del exoma se realizó en el Complexo Hospitalario Universitario de Santiago de Compostela (España) con el programa SureSelect Clinical Research Exome V2 de Agilent. Resultados. En la secuenciación del exoma se detectaron variantes genéticas en ambos casos en comparación con la secuencia de referencia. En las muestras de ambos pacientes se identificó una variante heterocigota consistente en una transición de citosina a timina en la posición c.236 (NM_000174.4) que provoca el cambio del aminoácido treonina por isoleucina en la posición p.79 del dominio extracelular repetitivo rico en leucina (subunidad GPIba del complejo de la glicoproteína Ib-IX-V) y que podría provocar el cambio conformacional del receptor principal del ligando Ib alfa, así como hiperagregación plaquetaria y trombosis. Esta variante no ha sido descrita previamente en pacientes con SPP. Conclusión. La mutación identificada en las muestras estudiadas podría estar relacionada con el SPP considerando la importancia de la glicoproteína IX en las funciones plaquetarias.
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Objective:To investigate the predictive value of serum C-type lectin-like receptor 2 (CLEC-2) combined with insulin resistance in the outcome of patients with acute ischemic stroke (AIS) after intravenous thrombolysis.Methods:Patients with AIS received alteplase intravenous thrombolytic therapy in the Department of Neurology, the Second Affiliated Hospital of Nantong University from October 2019 to March 2021 were enrolled retrospectively. According to the modified Rankin Scale score at 90 d after onset, they were divided into good outcome group (0-2) and poor outcome group (>2). Homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate insulin resistance. Person correlation analysis was used to determine the correlation between CLEC-2 and HOMA-IR. Multivariate logistic regression analysis was used to determine the correlation between serum CELC-2, HOMA-IR and the outcome after intravenous thrombolysis. Receiver operating characteristic (ROC) curve was used to determine the predictive value of serum CLEC-2 combined with HOMA-IR for poor outcome after intravenous thrombolysis. Results:A total of 100 patients were enrolled (56 males, 56.0%; aged 70.6±10.86 years, range 49-83 years). The baseline National Institutes of Health Stroke Scale (NIHSS) score was 10.00±6.36. Senenty-four patients (74.0%) had a good outcome and 26 (26.0%) had a poor outcome. Person correlation analysis showed that there was a significant positive correlation between serum CLEC-2 and HOMA-IR ( r=0.523; P<0.001). Multivariate logistic regression analysis showed that after adjusting for confounding factors (C-reactive protein, baseline NIHSS score, onset-to-needle time), the highest quartile of serum CLEC-2 (compared with the lowest quartile: odds ratio [ OR] 4.836, 95% confidence interval [ CI] 1.105-21.169; P=0.036) and the highest quartile of HOMA-IR (compared with the quartile 1-3: OR 15, 95% CI 2.647-30.722; P=0.002) were the independent risk factors for the poor outcome in patients with AIS after intravenous thrombolysis. ROC curve analysis showed that the area under the curve for serum CLEC-2 combined with HOMA-IR to predict poor outcome was 0.785 (95% CI 0.688-0.883; P<0.001), the optimal cut-off value was 0.72, and the sensitivity and specificity were 76.0% and 95.0%, respectively. Conclusion:CLEC-2 combined with insulin resistance has a certain predictive value for the poor outcome of patients with AIS after intravenous thrombolysis.
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Acute pancreatitis (AP) is an exocrine inflammatory disease of the pancreas, the pathophysiological mechanism of AP remains unclear. Autophagy is an important pathway of metabolic degradation in cells, and autophagy impairment is closely associated with the development and progression of many diseases. Recent studies have found that the process of autophagy is abnormal in AP, with impaired fusion of autophagosome and lysosome and a significant reduction in the degradation function of autolysosome. Abnormal activation of pancreatic enzymes and inflammatory response is the key event in the initiation of AP, and abnormal autophagy is closely associated with these two events. The study of the upstream and downstream mechanisms of autophagy dysfunction in AP may help to find new molecular targets and strategies for the treatment of AP.
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Objective To investigate the relationship between the changes of plasma thromboxane B2 (TXB2),6-keto-prostaglandin 1 α (6k-PGF1 α) and positive platelet α-granule membrane glycoprotein (CD62P) in patients with acute cerebral infarction.Methods 160 patients with acute cerebral infarction (case group) and 80 healthy subjects were enrolled in our hospital from August 2016 to August 2018.The plasma levels of 6k-PGF1α,CD62P and TXB2 were measured and analyzed.Subgroup analysis was performed on patients with cerebral infarction with different trial of org 10172 in acute stroke treatment (TOAST) classification,National Institute of Health Stroke Scale (NIHSS) score,and prognosis outcome.Results The plasma levels of 6k-PGF1α,CD62P and TXB2 in the case group were significantly higher than those in the control group (P ＜ 0.05).The plasma levels of 6k-PGF1 α,CD62P and TXB2 in mild,moderate and severe groups were gradually increased (P ＜ 0.05).The plasma levels of 6k-PGF1 α,CD62P and TXB2 in patients with small infarction,mid-infarction and large infarction were also gradually increased,with statistically significant difference (P ＜ 0.05);plasma 6k-PGF1 α,CD62P,TXB2 levels in patients with good prognosis were significantly lower than those in poor prognosis group (P ＜ 0.05).Conclusions The levels of plasma TXB2,6k-PGF1α and CD62P in patients with acute cerebral infarction are elevated,and are closely related to the patient's condition and prognosis.
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Objective To investigate the expression and clinical significance of serum neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and serum cystain C (CysC) in patients with renal tumor. Methods A total of 120 patients with renal tumor diagnosed in International Hospital of Zhejiang University from January 2016 and March 2016 was selected as the research object, and 60 patient medical volunteers were selected as control. The levels of NGAL and KIM-1 were determined by enzyme-linked immunosorbent assay ( ELISA) method, and the levels of serum CysC were determined by electrochemical luminescence method. The levels of NGAL, KIM-1, and CysC were compared, and their relevance was analyzed. Results The levels of NGAL, KIM-1, and CysC in research object were signifi-cantly higher than the control group; the levels of NGAL, KIM-1, and CysC in malignant tumor patients were significantly higher than the benign tumor;the levels of NGAL, KIM-1, and CysC in one level of ser-um tumor were lower than the two levels, three levels, and four levels of tumor patients. With the more Furhman grading, the levels of NGAL, KIM-1, and CysC were higher, the differences were statistically sig-nificant (P<0. 05). The levels of serum NGAL, KIM-1, and CysC were significantly related to renal dam-age degree. The levels of serum NGAL were significantly positively related to KIM-1 and CysC ( r= 0. 812 and 0. 765 ) . The levels of serum KIM-1 expression were significantly positively related to CysC ( r =0. 832) (P<0. 05). Multiple regression analysis showed that the levels of serum NGAL, KIM-1, and CysC were significantly related to patients with renal tumor Furhman classification ( P<0. 05 ) . Conclusions The levels of NGAL, KIM-1 and CysC were significantly increased in patients with renal tumor renal tumor, the higher the clinical stage, the higher expressive level, and were significantly related to renal damage de-gree. NGAL, KIM-1, and CysC can be used as the diagnostic markers of renal tumor.
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Objective To investigate the prognostic value of serum neutrophil gelatinase-associated lipid transport protein (NGAL) and renal injury molecule 1 (KIM-1) in assessing neonatal sepsis with a-cute renal injury. Methods A total of 63 cases of renal injury with neonatal sepsis was collected from De-partment of Pediatrics, Affiliated Children's Hospital of Capital Institute of Pediatrics. The general condition of the patients, and neonatal critical case score ( NCIS) were recorded. The expressions of NGAL and KIM-1 in serum of all children were measured by venous blood and urine. Each case was followed up for 28 days to track the death of newborns. Pearson correlation analysis was used to test the correlation among NGAL, KIM-1, and NCIS;Multivariate regression analysis was used for NGAL, KIM-1, and other risk factors asso-ciated with neonatal sepsis kidney injury 28 days mortality. Receiver operating characteristic ( ROC) curve was used to compare the value of NGAL and KIM-1 in the prognosis of neonatal sepsis renal injury. The val-ues of NGAL and KIM-1 in the prognosis of neonatal sepsis renal injury were analyzed by ROC curve. Re-sults ⑴ After 28 days of follow-up, 63 cases of neonatal sepsis, and 22 died were found, which was ac-counted for 34. 92 percent of the total. ⑵ Compared to the survival group, the expressions of NGAL and KIM-1 in the death group were increased ( P<0. 01 ) . ⑶ Pearson correlation analysis showed that NGAL and KIM-1 expressions in peripheral blood were negatively correlated with NCIS. ⑷Multivariate regression analysis showed that NGAL and KIM-1 were independent risk factors for neonatal sepsis kidney injury ( P<0. 01). ⑸ ROC curve analysis showed that the area under the curve of NGAL and KIM-1 was 0. 79 (95％CI:0. 75-0. 93), and 0. 84 (95％ CI:0. 71-0. 90), NGAL and KIM-1 were better than single detection with NGAL, or KIM-1, area under curve (AUC) was 0. 89 (95％ CI:0. 78-0. 94) (P<0. 01). Sensitiv-ity of KIM-1 was superior to that of NGAL, and specificity of NGAL was superior to KIM-1. The sensitivity and specificity of both were better than single detection with NGAL and KIM-1. Conclusions NGAL and KIM-1 have good predictive value in assessing neonatal sepsis kidney injury mortality.
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Objective To investigate the significance of combined detection of urine neutrophil gelatinase-associated lipocalin (NGAL),kidney injury molecule-1 (KIM-1),and interleukin-18 (IL-18) in early diagnosis of contrast-induced nephropathy (CIN).Methods A total of 367 hospitalized patients undergone CT angiography (CTA) was enrolled into this study from May 2015 to February 2017.According to the European Society of Urology and radiology (ESUR) guidelines 2011,CIN was diagnosed in 31 patients (CIN group),and a total of 30 non CIN patients were randomly selected as non-CIN group.Another 30 patients who were hospitalized during the same period without contrast media were randomly selected as the control group.The changes of serum creatinine (Scr),urinary NGAL,KIM-1,and IL-18 were detected before and 8 h,24 h and 72 h after CTA.The same serum and urinary samples were collected at the time of admission in the control group.The sensitivity and specificity values of combined urinary NGAL,KIM-1,and IL-18 in early diagnosis CIN were evaluated by the under area of the receiver operating characteristic curves and area under curve (AUC).Results (1) According to ESUR guidelines 2011,CIN was diagnosed in 31 patients (8.4％).(2) At 8h after CTA,the levels of urinary NGAL,KIM-1,and IL-18 were significantly increased in the CIN group,compared with non-CIN group (P ＜ 0.05).(3) The AUC,sensitivity and specificity for early diagnosis of CIN were 0.999,96.8％,and 100％,when combine urinary NGAL,KIM1,and IL-18,at 8h after CTA.AUC for 24 h,and 72 h after contrast media injection approach to 1.0,at this time sensitivity and specificity were 100％,and 100％,respectively.Conclusions (1) At 8 h after CTA,the urinary NGAL,KIM-1,and IL-18 levels were significantly increased in the CIN group.(2) The predictable time of CIN onset determined by urinary NGAL,KIM-1,and IL-18 was earlier than Scr,and the sensitivity and specificity is higher in these biomarkers than Scr in early diagnosis of CIN.Especially combination of urinary NGAL,KIM-1,and IL-18 is more valuable in predicting the sensitivity and specificity of the diagnosis,and can be used as an indicator for early diagnosis of CIN.
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Objective To evaluate the safety and efficacy of low-dose platelet glycoprotein Ⅱb/Ⅲa antagonist tirofiban on preventing reocclusion during mechanical thrombectomy (MT) for in situ thrombosis(IST).Methods It is a retrospective cohort study, and 112 patients treated with MT, from the Nanjing Prospective Stroke Registration, were enrolled from February 2014 to October 2014. During MT, if angiography after a successful recanalization(defined as Thrombolysis In Cerebral Infarction(TICI) 2b/3) showed residual stenosis at the site of occlusion, additional angiographies were made every 10 min for 30 min.Then, if angiography displayed reocclusion in the corresponding vessels, a repeat recanalization was operated, followed by a low dose intra-arterial tirofiban infusion. MRA or CT angiography (CTA) was implemented to identify intracranial atherosclerosis (ICAS) 5-7 days after the procedure. The patients with confirmed ICAS were enrolled in the IST group. The rest were enrolled in the non-in situ thrombosis (NIST) group.Results A total of 80 patients with acute cerebral infarction were enrolled in the study. IST rate was 32.5%(26/80).All IST patients were confirmed ICAS by follow-up vascular imaging. Instant reocclusion after successful recanalization was significantly more common in the IST group(57.7%(15/26) vs 3.7%(2/54);χ2=30.568, P=0.000) than in the NIST group.In the case of the efficacy and safety of low-dose intra-arterial tirofiban infusion, 82.6%(19/23) of the reocclusion patients eventually accomplished TICI 2b/3, the rest 17.4%(4/23) of the cases were intractable to the procedure and needed rescue stent implantation.The modified Rankin Scale scores in patients infusing tirofiban were superior to the unused patients in 90 days. There was no patient with symptomatic intracranial hemorrhage after the procedure. Conclusions Patients with IST have higher cerebrovascular reocclusion rate during MT. After MT, low-dose intra-arterial tirofiban infusion may prevent reocclusion, and the prognosis is better.
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Immunotherapy is revolutionizing the treatment of non-small cell lung cancer (NSCLC).Programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) monoclonal antibodies have recently led to significant and durable improvements in the clinical outcome of NSCLC,and the anti-PD-1 antibody has been approved to use in first-line and second-line treatment of NSCLC.However,there are still many problems to be solved.The role of PD-L1 as a predictive biomarker remains unclear.Combination treatment models are being explored.This review summarizes the clinical efficacy,drug adverse reaction,combined treatment,and potential immune biomarkers of anti-PD-1/PD-L1 antibody research progress in the treatment of NSCLC.
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Background Genetic mutation remains to be the most common cause of congenital cataract.Whole exon sequencing technology is an ideal method to detect the pathogenic gene mutations.Objective This study was to identify the pathogenic gene in a Chinese autosomal dominant congenital cataract (ADCC) family by whole-exome sequencing.Methods This study complied with Helsinki Declaration and the protocol was approved by Ethic Committee of Peking University Third Hospital.Informed consent was obtained from each subject before any medical examination.A cross-sectional study was designed.A Chinese ADCC family with 4 generations and 48 members were enrolled in Peking University Third Hospital,of which Ⅰ1 and Ⅰ2 died.The periphery blood of 8-10 ml was collected from each member of Ⅱ,Ⅲ and Ⅳ generations for the high throughput sequencing of genes using whole exon trapping and new sequencing technology,and the sequencing results were compared with the data of human HA PMAP8,dbSNP130 and 1000 Genome Project database.The synonymous mutation was filtered after reported common variants,and the false positive results of explicit sequencing were finally excluded by Sanger sequencing and then the candidate genes were identified.The mutation genes were screened to determine the pathogenic gene of this ADCC family.Results Eleven ADCC patients were found in this family,and the patients distributed in each generation with an equal chance for involvement in male and female subjects,which conformed to an autosomal dominant inheritance pattern.All the patients were nuclear cataract.Genome-wide whole-exome sequencing found that major intrinsic protein (MIP) gene was known genes of ADCC in initially identified candidate genes,so the Sanger was used to verify the MIP gene.The heterozygous mutation of MIP gene (chr12:56845250 C ＞ T) appeared to be the pathogenic cause of this ADCC family.The mutation occurred in the splice sites of the gene,resulting in the fourth exon coded-61 amino acids are replaced by leucine,histidine and serine,which lead to the abnormal truncated proteins.Conclusions The heterozygous mutation of MIP gene is the molecular pathogenesis of this Chinese ADCC family.
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ObjectiveTo explore the clinical significance of serum hepatitis B virus large surface protein (LHB), HBsAg, hepatitis B virus (HBV) DNA, and alanine aminotransferase (ALT) levels and their correlation with liver inflammation activity in patients with chronic hepatitis B (CHB). MethodsOne hundred and two HBeAg-positive patients with CHB who visited the People′s Hospital of Taizhou from January 2011 to December 2014 were enrolled in the study, and were divided into mild inflammation group (G0-1) and severe inflammation group (G2-4) according to the grade of liver inflammation activity. Continuous data were expressed as x±s; the t-test was applied for comparison between two groups, and analysis of variance was applied for comparison between multiple groups. The Spearman rank correlation test was applied to investigate the correlation between LHB, HBsAg, HBV DNA, and ALT levels and the grade of liver inflammation activity. The area under the receiver operator characteristic (ROC) curve (AUC) was applied to evaluate their diagnostic values. ResultsThe level of LHB tended to increase with the increasing HBV DNA. The AUCs of LHB, HBsAg, ALT, and HBV DNA for diagnosing severe liver inflammation were 0.763, 0.756, 0.702, and 0.581, respectively, and the diagnostic efficiency of LHB, HBsAg, and ALT reached a moderate level (AUC of the ROC curve 0.70-0.90); the diagnostic values of serum LHB and HBsAg levels for severe liver inflammation were higher than that of serum ALT level. The optimal cut-off for serum LHB level to diagnose severe inflammation was 24.6, and the corresponding sensitivity and specificity were 73.4% and 60.3%, respectively. ConclusionSerum LHB and HBsAg levels have certain predictive values for severe liver inflammation in HBeAg-positive patients with CHB.
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Objective:To explore influence of preoperative tirofiban usage and using time on blood flow of infarct re-lated artery (IRA) in patients with acute ST elevation myocardial infarction (ASTEMI ) undergoing emergency di-rect percutaneous coronary intervention (PCI ) .Methods:A total of 266 ASTEMI patients undergoing direct PCI from Jan 2009 to Oct 2012 ,were randomly divided into tirofiban group (n=134 ,received preoperative tirofiban us-age for PCI) and routine treatment group (n=132 ,didn't receive tirofiban during PCI) .According to percutaneous using time of tirofiban tirofiban group was divided into <3h group (n= 63) and ≥3h group (n= 71) ;TIMI blood flow of IRA ,before and after PCI were compared among different groups .Results:Compared with routine treat-ment group before PCI ,there were significant rise in percentages of TIMI grade 3 (10.6% vs .20.9% ) in tirofiban group ,P=0.028 ;after PCI ,percentage of TIMI grade 3 in tirofiban group was more significantly rose than that of routine treatment group (78.8% vs .92.5% ,P=0.001);in tirofiban group ,blood flow of IRA before PCI in <3h group was significantly improved compared with ≥3h group (TIMI grade 2 + 3 ,63.5% vs .29.6% , P<0.01) . Conclusion:Early tirofiban usage can improve TIMI blood flow of IRA before and after PCI in ASTEMI patients , the earlier it′s used ,the more significant effect it has .
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Objective To investigate the clinical value of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in the treatment and therapeutic effect evaluation of patients with an exacerbation of chronic obstructive pulmonary disease.Methods The levels of serum sTREM-1,procalcitonin (PCT) and C-reactive protein (CRP) were determined by enzyme-linked immunosorbent assay (ELISA) in 49 exacerbation of chronic obstructive pulmonary disease (COPD) subjects [acute exacerbation of chronic obstructive pulmonary disease (AECOPD) group],49 stable COPD subjects(sCOPD group) after treatment and 49 healthy volunteers as healthy control group.The levels of sTREM-1,PCT and CRP in different groups were compared and the relationship between the level of sTREM-1 in AECOPD and sCOPD groups,and PCT,and CRP was analyzed,respectively.Results The content of sTREM-1,PCT and CRP between different groups had significant difference(P ＜0.05).The level of sTREM-1 in both AECOPD and sCOPD groups was significantly positive correlated with PCT (P ＜ 0.05) and negative correlated with CRP (P ＞ 0.05).Conclusions For guiding the treatment and curative effect evaluation of patients with AECOPD,sTREM-1 has important clinical reference value.
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Objective To investigate the respiratory burst function of neutrophils in very low birth weight infants (VLBWI).Methods Twenty two VLBWI was divided into two groups:neonatal respiratory distress syndrome (NRDS) and non NRDS (11 in each).The respiratory burst function of neutrophils in the peripheral blood of VLBWI within 48 hours after birth was determined using the flow cytometrydihydrorhodamine 1,2,3 method before and after the chemical stimulation of phorbol-12-myrismte 14 acetate (PMA),and the gp91Phox was also measured in resting neutrophils by flow cytometry.Twenty healthy term neonates served as controls.Mann-Whitney U test was used for statistical analysis.Results Before the stimulation of PMA,the percentage of activated neutrophils of VLBWI [(49.10±20.19) ％] producing a respiratory burst was higher than that of term neonates [(18.73 ±6.81) ％] (Z--4.911,P=0.000),however,after the stimulation of PMA,the percentage of activated neutrophils of VLBWI [(96.58 ± 3.44) ％] was lower than that of term neonates [(99.20±0.62) ％] (Z--3.186,P=0.001),and the stimulation index (SI) of VLBWI (171.40 ± 103.35) was lower than that of term neonates (306.30 ± 138.47),with significant difference (Z=-3.413,P=0.001).The geometric mean of gp91Phox in VLBWI (21.66± 19.87) was higher compared with term neonates (19.60±8.03),however,the difference was not significant (P=0.350).The percentage of neutrophils that expressed gp91Phox [(56.11 ± 29.40) ％] was lower in VLBWI than that in term neonates [(80.14± 14.87) ％],with significant difference (Z=-2.374,P=0.018).Before the stimulation of PMA,the percentage of activated neutrophils of VLBWI with NRDS (63.40± 16.45) ％] was higher than that of VLBWI without NRDS [(34.80± 11.65) ％],with significant difference (Z=-3.382,P=0.001),the SI of VLBWI with NRDS (129.46 ± 75.36) was significantly lower than that of VLBWI without NRDS (213.35 ± 113.49) (Z=-2.331,P=0.020).Conclusions Neutrophils producing a respiratory burst in both VLBWI and term neonates are active without stimulation of PMA,while the phenomenon is more obvious in VLBWI.Neutrophils in VLBWI and term infants can be activated by the stimulation of PMA,and express gp91Phox.The activation and gp91Phox expression of neutrophils in VLBWI with NRDS tend to be lower than those in VLBWI without NRDS.
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Objective To investigate the effect and significance of hyperbaric oxygenation in down-regulation of platelet membrane glycoproteins CD31 and CD62p in rats of traumatic brain injury (TBI).Methods Fifty-six SD rats were randomly distributed into TBI group,hyperbaric oxygenation group,and sham group by the lottery method.Furthermore,TBI group and hyperbaric oxygenation group were subgrouped at 6,48,and 96 hours.There were 8 rats per group.The rat models of severe TBI were induced by lateral fluid percussion.Levels of CD31 and CD62p were measured in all groups by flow cytometry.Results At 6,48 and 96 hours,expressions of CD31 (30.8 ± 8.9,32.5 ± 9.2 and 29.0 ±5.0) and CD62p (34.5 ±9.1,33.9 ±7.5 and 30.4 ±6.4) in TBI group were significantly higher than those (18.9-± 5.5,19.5 ± 6.1) in sham group (P ＜ 0.05).At 96 hours,expression of CD31 (22.7 ±5.5) in hyperbaric oxygenation group was significantly lower than 29.0 ± 5.0 in the TBI group (P ＜0.05).At 48 and 96 hours,expressions of CD62p (26.1 ± 5.8,23.6 ± 5.7) in hyperbaric oxygenation group were significantly lower than 33.9 ± 7.5 and 30.4 ± 6.4 in TBI group (P ＜ 0.05).Conclusions Platelet activation is enhanced in the acute phase after TBI.But platelet activation may be relieved with hyperbaric oxygenation,which is conducive to inhibiting microthrombosis and mitigating secondary brain injury after TBI.
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Objective To investigate the effects of supplementing qi and activating blood circulation method(YQHX) on platelet inhibition rate and platelet membrane glycoprotein in elderly patients with unstable angina pectoris undergoing percutaneous coronary intervention(PCI).Methods Totally 177 elderly patients with unstable angina(qi deficiency and blood stasis syndrome) pectoris were randomized into two groups:90 cases in the treatment group and 87 cases in the control group.Both groups received conventional western medicinal treatment,for 14 days but YQHX was added to the treatment group.Platelet inhibition rate and platelet membrane glycoprotein were measured before and 14 days after treatment.Results After 14 days of treatment,the platelet inhibition rates induced by arachidonic acid (AA) and adenosine diphosphate (ADP) were significantly increased in the treatment group in comparison to pre-treatment and to control group respectively(P＜0.01).The prevalence of aspirin and clopidogrel resistance were lower in the treatment group than in the control group(8.9％ vs.21.8％,11.1％ vs.25.3％,both P＜0.05).After 14 days of treatment,the expression rates of CD62p,CD63 and PAC-1 were significantly lower in the treatment group than in pre-treatment and control group respectively (P＜0.01).Conclusions YQHX might effectively inhibit the platelet function and reduce the prevalence of aspirin and clopidogrel resistance in elderly patients with unstable angina pectoris undergoing the percutaneous coronary intervention.
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Objective To analyze gene mutations of a Niemann-Pick disease type C (NPC) proband,and carry out prenatal diagnosis for the family.Methods The coding regions of NPC1 gene in the proband (late-infantile form) and white blood cell (WBC) in peripheral blood of its parents were amplified by polymerase chain reaction and direct DNA sequencing in both directions was performed.The sequencing results were compared with human NPC1 gene sequence (NM_000271) in GenBank,and sequences of mutated exons were determined.Direct sequencing was used on 50 normal Chinese individuals' DNA samples (control) to exclude mutation's single nucleotide polymorphism (SNP).An inter-species alignment of homologous NPC1 proteins was performed using ClustalX 1.81 software.During the second pregnancy of the proband's mother,the amniotic fluid was obtained at 18 weeks of gestation and the amniocytes were cultured for gene mutation analysis.Neonate's DNA of WBC in peripheral blood was also extracted for NPC1 gene analysis.Results Mutation analysis of NPC1 gene revealed two novel heterozygous mutations (c.2284-2287 delCTCT and p.V959G) in the proband,which originated from her father and mother,respectively.These two mutations were absent in the control,suggesting that these mutations were not SNP.While comparing with the amino acid in NPC1 protein of human,mouse,rat,rabbit,cat and pig,it revealed that p.V959 belonged to a conservative amino acid region and the missense mutation of p.V959G may perturb the function of NPC protein.Neither mutation was found in DNA from amniotic fluid or from the cultivated amniocytes in the second pregnancy,suggesting a normal fetus.c.2284-2287 delCTCT and p.V959G mutation were not found in NPC1 gene analysis of WBC in peripheral blood of the neonate,which was consistent with the prenatal diagnosis.Conclusions PCR-direct sequencing could be used as genetic diagnosis for NPC proband and prenatal diagnosis for its family.The mutation p.V959G may be correlated to late infantile form of NPC.
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Objective To investigate the mechanism of endotoxin tolerance (ETT) through observing the expression of OX40 in liver tissues of ETT rats.Methods SD male rats were randomly divided into three groups:normal group (n=6),acute liver failure (ALF) group (n=24) and ETT group (n=24).Lipopolysacharide (LPS) 0.1 mg/kg (ETT groups) or 0.9 ％NaC1 (ALF groups) was administered by five consecutive intraperitoneal injections at 24 h intervals,and at the sixth day,all animals were treated with intraperitoneal injections of D-galactosamine (D-GalN) 800 mg/kg and LPS 8 μg/rat.Blood and liver tissue were collected at 6,12,24 and 48 hours after the injection of D-GalN/LPS.The gene expression of OX40 in the liver was measured by reverse transcription-polymerase chain reaction (RT-PCR).The protein expression of OX40 was estimated by Western blot.The tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were determined by enzyme-linked immunosorbent assay (ELISA).The data analysis was performed by one-way ANOVA,lease significant difference (LSD) and Dunnett's T3 test.Results The expressions of TNF α and IL-6 were both significantly lower in ETT group compared to ALF group,but still higher than that of control group.The gene expressions of OX40 peaked at 12 hours and decreased gradually in ALF group.The gene expressions of OX40 were significantly lower in ETT group compared to ALF group (6 h:F=5.027,24 h:F=5.539,48 h:F=5.011,all P＜0.05; 12 h:F=36.688; P＜0.01),but still higher than that of normal group.The tendency of OX40 protein expression in ALF group was peaked at 12 hours and decreased at 24 hours.In ETT group,the expression of OX40 was lower,and the difference between ETT group and ALF group had statistical significance (6 h:F=8.658,P＜0.05; 12 h:F=34.611,24 h:F=28.176,48 h:F=16.747; all P＜0.01).Conclusions The level of OX40 is increased in ALF group,while the expressions of OX40,TNF-α and IL-6 are lower in ETT group,which suggested that OX40 may play an important role in the process of ETT.
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Objective To investigate the expression of sialic acid-binding immunoglobulin-like lectin-1 (Siglec-1) in the peripheral blood mononuclear cells (PBMCs) in patients with rheumatoid arthritis (RA),osteoarthritis (OA) and healthy controls and to explore the relationship between Siglec-1 expression and disease activity in RA.Methods Siglec-1 protein and mRNA levels were measured by flow cytometry and real-time quantitative reversetranscription-polymerase chain reaction (qRT-PCR) in 42 RA patients,28 OA patients and 26 healthy controls,respectively.The correlation studies between Siglec-1 and disease activity score 28 (DAS28) or C-reactive protein were performed.T-test was used for comparisons between groups and Pearson's correlation test was used for correlation analysis.Results The percentage of Siglec-1 positive cells of PBMCs in RA group [(15.2±7.6)％] was significantly higher than that in the OA group [(2.3 ±2.6)％] or healthy controls [(2.1±1.6)％,t=8.615,8.661; all P＜0.01].And the major cell type in PBMCs that expressed Siglec-1 was monocytes.The relative Siglec-1 mRNA expression in PBMCs in the RA group (3.4±1.5) was also significantly higher than that in the OA group (1.2±0.4) or healthy controls [(1.0± 0.4),t=3.446,3.966; all P＜0.05].But no significant differences of Siglec-1 protein and mRNA between the OA group and healthy controls were found.Furthermore,positive correlations between Siglec-1 protein and DAS28 or hs-CRP were found in RA patients (r=0.89,P＜0.01; r=0.48,P＜0.01).Conclusion PBMCs are activated which are characterized by elevated expression of Siglec-1 in RA patients.Circulating Siglec-1 may be considered as a potential noninvasive biomarker for monitoring disease activity in RA.
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Platelet membrane glycoproteins play a key role in the processes of platelet adhesion,activation and aggregation and thrombosis.Many studies have shown that platelet membrane glycoprotein gene polymorphisms are associated with ischemic stroke.This article reviews the relationship between platelet membrane glycoprotein gene polymorphisms and ischemic stroke.