Longitudinal variation of circulating Inc‐ITSN1‐2: A novel biomarker reflecting disease severity,inflammation, recurrence,and death risk in acute ischemic stroke patients

BackgroundLong noncoding RNA intersectin 1–2 (lnc‐ITSN1‐2) regulates inflammation and neuronal apoptosis; meanwhile, the latter two factors participate in the pathogenesis of acute ischemic stroke (AIS). Therefore, this study detected lnc‐ITSN1‐2 at multiple time points, aiming to explore its longitudinal variation and clinical value in the management of AIS patients.MethodsThe current study enrolled 102 AIS patients, then detected their lnc‐ITSN1‐2 in peripheral blood mononuclear cell (PBMC) at baseline (D0), day (D)1, D3, D7, month (M)1, M3, M6, and year (Y)1 after admission using RT‐qPCR. Additionally, lnc‐ITSN1‐2 in PBMC of 50 controls was also detected.ResultsLnc‐ITSN1‐2 was up‐regulated in AIS patients than that in controls (p < 0.001). Lnc‐ITSN1‐2 positively associated with NIHSS score, TNF‐α, and IL‐17A (all p < 0.050) but was not linked with IL‐6 (p = 0.093) in AIS patients. Notably, lnc‐ITSN1‐2 was gradually increased from D0 to D3; while it switched to decrease from D3 to Y1 in AIS patients. Lnc‐ITSN1‐2 disclosed similar longitudinal variation during 1 year in non‐recurrent (p < 0.001), recurrent (p = 0.001), and survived patients (p < 0.001), while the variation of lnc‐ITSN1‐2 in died patients was not obvious (p = 0.132). More importantly, lnc‐ITSN1‐2 at D0, D3, D7, M1, M3, M6, and Y1 was higher in recurrent AIS patients than that in non‐recurrent AIS patients (all p < 0.050); moreover, lnc‐ITSN1‐2 at D3, D7, M1, M3, and M6 was up‐regulated in died AIS patients than AIS survivors (all p < 0.050).ConclusionThe dynamic variation of Inc‐ITSN1‐2 could serve as a biomarker reflecting disease severity, inflammatory cytokines, recurrence, and death risk in AIS patients.     

The longitudinal changes of serum JKAP and IL‐17A,and their linkage with anxiety,depression, and cognitive impairment in acute ischemic stroke patients

BackgroundOur previous study discovers that Jun N‐terminal kinase pathway‐associated phosphatase (JKAP) is dysregulated and negatively links with the disease severity in acute ischemic stroke (AIS) patients. This study intended to further evaluate the linkage of JKAP and interleukin (IL)‐17A with anxiety, depression, and cognitive impairment in AIS patients.MethodsSerum JKAP and IL‐17A levels in 120 AIS patients at admission, 1st (D1), 3rd (D3), 7th (D7) day after admission, and from 20 controls, were detected by ELISA. Hospital Anxiety and Depression Scale (HADS) and Mini‐Mental State Examination (MMSE) were assessed in AIS patients at discharge.ResultsJKAP (p < 0.001) was reduced, but IL‐17A (p < 0.001) was increased in AIS patients versus controls, and negatively correlated with each other in AIS patients (p = 0.014). In AIS patients, JKAP was reduced from baseline to D1 and then increased to D7 (p < 0.001), while IL‐17A exhibited an opposite trend (p < 0.001). Notably, JKAP at D3 was negatively linked with HADS‐anxiety score (p = 0.044), then decreased JKAP at D3 (p = 0.017) and D7 (p = 0.037) related to increased anxiety occurrence. However, JKAP was not linked to HADS‐depression score or depression occurrence. Besides, JKAP at multiple time points were positively associated with MMSE score (all p < 0.05); decreased JKAP at D3 (p = 0.017) and D7 (p = 0.026) related to raised cognitive impairment occurrence.ConclusionJKAP initially decreases then shows an increasing trend after disease onset, and its decrement relates to elevated IL‐17A, anxiety and cognitive impairment in AIS patients.     

A novel circulating biomarker lnc‐MALAT1 for acute myocardial infarction: Its relationship with disease risk,features, cytokines,and major adverse cardiovascular events

ObjectiveLong noncoding RNA MALAT1 (lnc‐MALAT1) modulates atherosclerotic progression, myocardial ischemia injury, and systematic inflammation, which may be closely involved in acute myocardial infarction (AMI) pathogenesis. Thus, the current study intended to explore the relationship of lnc‐MALAT1 to disease risk, features, cytokines, and prognostication in AMI patients.MethodsThis multicenter study consecutively enrolled 160 newly diagnosed AMI patients and 50 controls (angina pectoris patients). Their peripheral blood mononuclear cells were obtained to measure lnc‐MALAT1 by RT–qPCR. Serum cytokines in AMI patients were detected by ELISA. In addition, AMI patients were followed up for major adverse cardiovascular event (MACE) risk evaluation.ResultsLnc‐MALAT1 was higher in AMI patients than in controls (median: 2.245 vs. 0.996, p = 0.004), and it also presented a good capacity for differentiating AMI patients from controls with an area under the curve of 0.823. Lnc‐MALAT1 was positively related to C‐reactive protein (p = 0.005), low‐density lipoprotein cholesterol (p = 0.022), cardiac troponin I (p = 0.021), and infarct size (p = 0.007), but not other biochemical indexes in AMI patients. Meanwhile, lnc‐MALAT1 was positively associated with tumor necrosis factor‐alpha (p = 0.001), interleukin (IL)‐6 (p = 0.031), IL‐17A (p = 0.042), vascular cell adhesion molecule‐1 (p = 0.004), and intercellular adhesion molecule‐1 (p = 0.021) among AMI patients. Importantly, after categorization, lnc‐MALAT1 high (vs. low) was related to an elevated MACE accumulation rate (p = 0.035); furthermore, a higher lnc‐MALAT1 quartile showed a trend to be linked with an increased MACE accumulation rate (p = 0.092).ConclusionLnc‐MALAT1 may serve as a biomarker for AMI risk, infarct size, inflammation and prognosis, but further validation by large‐scale studies is needed.     

Clinical value of serum JKAP in acute ischemic stroke patients

BackgroundJun N‐terminal kinase pathway‐associated phosphatase (JKAP) regulates neuronal function, T helper (Th) 1/2/17 cell differentiation, and inflammatory process, but its clinical role in acute ischemic stroke (AIS) patients remains unclear. Hence, this study intended to evaluate JKAP level and its relationship with disease severity, Th1, 2, 17 secreted cytokines, adhesion molecules, and prognosis of AIS patients.MethodsSerum JKAP of 122 AIS patients and 50 controls was detected by ELISA. For AIS patients only, Th1, 2, 17 secreted cytokines IFN‐γ, IL‐4, IL‐17; TNF‐α, ICAM‐1, and VCAM‐1 were also detected by ELISA.ResultsJKAP was decreased in AIS patients compared with controls (46.350 (interquartile range (IQR): 34.250–59.875) pg/ml vs. 84.500 (IQR: 63.175–113.275) pg/ml, p < 0.001), which could distinguish AIS patients from controls (area under curve (AUC): 0.810, 95% confidence interval (CI): 0.732–0.888). In AIS patients, JKAP negatively linked with the National Institutes of Health Stroke Scale (NIHSS) score (r_s  = −0.342, p < 0.001); besides, it was positively related to IL‐4 (r_s  = 0.213, p = 0.018) and negatively associated with IL‐17 (r_s  = −0.270, p = 0.003) but not related to IFN‐γ (r_s  = −0.146, p = 0.109). Furthermore, elevated JKAP associated with declined TNF‐α (r_s  = −0.219, p = 0.015) and ICAM‐1 (r_s  = −0.235, p = 0.009) but not related to VCAM‐1 (r_s  = −0.156, p = 0.085). Besides, declined JKAP was linked with 2‐year recurrence (p = 0.027) and 3‐year recurrence (p = 0.010) in AIS patients; while JKAP was not related to 1‐year recurrence or death risk (both p > 0.050).ConclusionJKAP may sever as a candidate prognostic biomarker in AIS patients, indicating its potency for AIS management.     

The lower expression of circulating miR‐210 and elevated serum levels of HIF‐1α in ischemic stroke; Possible markers for diagnosis and disease prediction

Background Stroke, either due to ischemia or hemorrhage, causes acute neurological damages to the brain. There is shortage of reliable biomarkers for ischemic stroke (IS), and we therefore investigated the serum concentrations of microRNA‐210 (miR‐210) and hypoxia inducible factor‐1α (HIF‐1α), as possible diagnostic and/or prognostic markers for IS.MethodsSerum samples were acquired from 52 IS patients and their healthy counterparts at five time points: upon admission, 24 and 48 h after admission, upon discharge and 3 months later. Serum levels of miR‐210 and HIF‐1α were respectively analyzed using real time RT‐PCR and ELISA. Diagnostic and prognostic accuracy tests were performed to assess the value of suggested biomarkers.ResultsIS patients demonstrated higher levels of serum HIF‐1α and lower miR‐210 in comparison to the healthy subjects. MiR‐210 was suggested to be a weak diagnostic biomarker at the time of admission (AUC = 0.61; p = 0.05), while HIF‐1α was an acceptable diagnostic marker for IS (AUC = 0.73; p < 0.0001). The higher expression of miR‐210 and lower levels of HIF‐1α were associated with better survivals in IS patients.ConclusionsSerum miR‐210 is a weak diagnostic marker of IS. Serum HIF‐1α is a better biomarker in diagnosing IS patients but further work in larger groups, including those with hemorrhagic stroke is necessary to confirm its diagnostic utility. Similarly, the prognostic potentiality of miR‐210 and HIF‐1α was acceptable but needs bigger sample size and longer follow‐up to be statistically confirmed.     

The prognostic values of serum markers in hepatocellular carcinoma after invasive therapies based on real‐world data

Background and aimsHepatocellular carcinoma (HCC) is one of the most common malignancy with poor prognosis, and the mortality rate remains high. More than 70% of HCC patients have recurrence within 5 years after treatment. The purpose of this study is to evaluate the prognostic values of serum markers with retrospective data.MethodsWe applied real‐world data (RWD) to analyze the prognostic values of six serum markers for HCC patients after treatment, including α‐fetoprotein (AFP), α‐fetoprotein‐L3 (AFP‐L3), Golgi protein73 (GP73), alanine aminotransferase (ALT), albumin (ALB), and total bilirubin (TBil). A total of 268 cases were enrolled to analyze recurrence‐free survival (RFS), and 104 cases were used to analyze overall survival (OS).ResultsOur results demonstrated that patients with higher AFP and AFP‐L3 had shorter RFS (p = 0.016 and 0.004), while higher GP73, ALT, and TBil experienced longer RFS (p = 0.000, 0.020, and 0.019). Patients with high‐level GP73, ALT, TBil, and low‐level ALB had significantly higher mortality rate (p=0.035, 0.008, 0.010, and 0.005). Multivariate analysis revealed that GP73 (HR = 1.548, p = 0.001) and ALT (HR = 1.316, p = 0.046) were identified as independent prognostic factors for RFS, ALB (HR = 0.127, p = 0.007), and ALT (HR = 0.237, p = 0.01) were identified as independent prognostic factors for OS. Subgroups analysis showed that GP73 had better prognostic values than other serum markers in early‐stage HCC (p = 0.023).ConclusionsOur study demonstrates that AFP, AFP‐L3, and GP73 can be used as prognostic indicators for predicting the recurrence of HCC, while liver function tests have better survival prediction values. GP73 can act as a promising prognostic marker for early‐stage HCC.     

Early platelet elevation after complete remission as a prognostic marker of favourable outcomes in favourable‐ and intermediate‐risk acute myeloid leukaemia: A retrospective study

ObjectivesPlatelet (PLT) recovery after chemotherapy is associated with the prognosis of patients with acute myeloid leukaemia (AML). This study aimed to explore the prognostic significance of early high PLT values in patients with de novo non‐M3 AML who achieved first complete remission (CR).MethodsA total of 206 patients with de novo non‐M3 AML were analysed in this retrospective study. A receiver operating characteristic (ROC) curve was used to determine the optimal PLT cut‐off. The overall survival (OS) and relapse‐free survival (RFS) were assessed using Kaplan‐Meier and Cox regression analyses.Results312×10⁹/L was confined as the cut‐off of the PLT count. The estimated 3‐year OS of patients with high PLT was higher than that of their counterparts (72.3% vs. 34.6%, p = 0.001). In subgroup analysis, patients with high PLT had better OS in the favourable‐ and intermediate‐risk (non‐adverse‐risk) AML (p = 0.001). The estimated 3‐year RFS for the high and low PLT groups was 75.1% and 45.7% respectively (p = 0.078). Multivariate analyses revealed that high PLT count was an independent favourable variable for OS (HR = 0.264, p < 0.001) and RFS (HR = 0.375, p = 0.011) in the non‐adverse‐risk group.ConclusionOur results showed that early high PLT count recovery at first CR in non‐adverse‐risk AML patients is a positive prognostic marker for survival outcomes.     

纳洛酮对急性缺血性中风神经功能的保护作用

目的 :观察加用纳洛酮治疗急性缺血性中风的效果。方法 :采用随机对照研究的方法 ,对急性缺血性中风后 72 h内入院 ,经头颅 CT或 MRI证实符合临床表现及相应影像学改变的患者 ,按诊断标准分成腔隙性和非腔隙性脑梗死两类 ,将非腔隙性脑梗死又分为轻型〔美国国立卫生院卒中量表评分 (NIHSS<8)〕及重型(NIHSS≥ 8)。在入院时及治疗 4周时行 NIHSS和改良 Rankin评分 (MRS)。对照治疗组给予尼莫地平或脑益嗪、脑复康、都可喜等常规脑保护剂药物 ;纳洛酮组加用盐酸纳洛酮注射液 1.6～ 2 .0 mg/ d静脉滴注 ,疗程3～ 4周 ;两组均根据病情给予常规抗凝、降纤、稀释或抗血小板聚集等治疗。结果 :16 8例患者入选 ,纳洛酮组71例 ,对照组 97例。纳洛酮组和对照治疗组治疗后神经功能缺损均有改善 ,但在腔隙性脑梗死患者中 ,加用纳洛酮并不比常规治疗更能有效地改善神经功能缺损的程度。在轻型非腔隙性脑梗死患者中 ,加用纳洛酮较对照治疗更能显著降低神经功能缺损评分的 NIHSS值 ,但 MRS差值与对照治疗组间差异无显著性 ;在重型非腔隙性脑梗死患者中 ,加用纳洛酮与对照治疗组相比能显著地降低 NIHSS及 MRS值。结论 :纳洛酮作为一种新型的脑保护剂可以显著改善脑梗死患者神经功能缺损程度 ,减轻残疾 ,对重症、神经功能     

Longitudinal change of Th1, Th2, and Th17 cells and their relationship between cognitive impairment,stroke recurrence,and mortality among acute ischemic stroke patients

BackgroundT‐helper (Th) cells regulate immunity and inflammation, and modulate cognitive impairment in both cardio‐cerebrovascular and neurological diseases. This study aimed to explore the correlation of longitudinal change of Th1/2/17 cells with cognitive impairment and prognosis in acute ischemic stroke (AIS).MethodsTh1/2/17 cells were detected by flow cytometry in peripheral blood samples from 150 AIS patients at admission (baseline), Day (D)1, D3, and D7 after admission, and from 30 controls. Mini‐Mental State Examination (MMSE) score among AIS patients at discharge was assessed. Stroke recurrence and mortality were evaluated.ResultsTh1 (p = 0.013) and Th17 cells (p < 0.001) but not Th2 cells (p = 0.105) were elevated in AIS patients versus controls. Th1 cells (p = 0.027) and Th17 cells (p < 0.001) but not Th2 cells (p = 0.227) were positively correlated with NIHSS score in AIS patients. Furthermore, Th1 and Th17 cells elevated from baseline to D3 and then decreased on D7 after AIS onset, while Th2 cells illustrated an opposite trend (all p < 0.001). Th17 cells on D1 (p = 0.011), D3 (p = 0.014), and D7 (p < 0.001) were correlated with lower MMSE score, and their levels on D3 (p = 0.033) and D7 (p = 0.004) were related to elevated cognitive impairment. Th1 and Th2 cells were not related to cognitive function (all p > 0.05). Additionally, Th17 cells at baseline, D1, D3, and D7 (all p < 0.05) were increased in recurrent patients versus non‐recurrent patients, and in survived patients versus dead patients, but Th1 or Th2 cells did not vary (all p > 0.05).ConclusionTh17 cells correlate with increased cognitive impairment, stroke recurrence, and mortality among AIS patients.