Overexpression of sirtuin 2 and its association with prognosis in acute ischemic stroke patients

BackgroundThis study aimed to investigate the correlation of sirtuin 2 (SIRT2) with acute ischemic stroke (AIS) risk, severity, inflammation, and prognosis.MethodsA hundred and sixty‐four first episode AIS patients and 164 age and gender matched non‐AIS patients with high‐stroke‐risk factors (controls) were enrolled. Peripheral blood was collected and serum was separated for SIRT2 and pro‐inflammatory cytokines detection by enzyme‐linked immunosorbent assay. AIS patients were continually followed up to 36 months or death, then recurrence‐free survival (RFS) and overall survival (OS) were calculated.ResultsSerum SIRT2 expression was increased in AIS patients compared to controls (p < 0.001), then receiver operative characteristic curve disclosed that the serum SIRT2 expression could differentiate AIS patients from controls with a good area under curve of 0.890 (95%CI: 0.854–0.926), a sensitivity of 78.7% and a specificity of 91.5% at the best cut‐off point. Serum SIRT2 expression was positively correlated with National Institute of Health stroke scale score (p < 0.001), serum tumor necrosis factor‐α (p < 0.001), interleukin (IL)‐6 (p = 0.012) and IL‐17 (p < 0.001) expressions in AIS patients. In addition, serum SIRT2 expression was elevated in recurrent/dead AIS patients compared to non‐recurrent/dead AIS patients (p = 0.025), and was also increased in dead AIS patients compared to survivors (p = 0.006). Moreover, RFS (p = 0.029) and OS (p = 0.049) were both worse in AIS patients with SIRT2 high expression compared to AIS patients with SIRT2 low expression.ConclusionSIRT2 may serve as a marker for AIS risk and prognosis in clinical practice.     

JNK pathway‐associated phosphatase in acute ischemic stroke patients: Its correlation with T helper cells,clinical properties,and recurrence risk

ObjectiveJKAP modifies T‐cell immune response and inflammation, also involves in cardia‐cerebrovascular disease etiology. This study intended to explore JKAP''s relation with T‐helper 1 (Th1), T‐helper 17 (Th17) cell levels, clinical properties, and recurrence‐free survival (RFS) in acute ischemic stroke (AIS) patients.MethodsA total of 155 AIS patients were analyzed. Serum JKAP, interferon‐gamma (IFN‐γ), and interleukin‐17A (IL‐17A) were detected by ELISA; then blood Th1 and Th17 cells were quantified by flow cytometry. Besides, 30 healthy subjects were enrolled as controls to detect JKAP, Th1, and Th17 cells.ResultsJKAP level was lower (p < 0.001), Th1 cells were not differed (p = 0.068), but Th17 cells were elevated in AIS patients versus controls (p < 0.001). Meanwhile, JKAP was negatively correlated with Th1 cells (p = 0.038), Th17 cells (P<0.001), IFN‐γ (p = 0.002), and IL‐17A (p < 0.001) in AIS patients. JKAP was negatively associated with the National Institutes of Health Stroke Scale (NIHSS) score (p < 0.001), but Th17 cells (p = 0.001), IFN‐γ (p = 0.035), and IL‐17A (p = 0.008) levels were positively associated with NIHSS score. Additionally, accumulating RFS was numerically longer in patients with JKAP Quantile (Q) 4 than patients with JKAP Q1–Q3 (p = 0.068), and numerically better in patients with JKAP Q3–Q4 than patients with JKAP Q1–Q2 (p = 0.069), but without statistical significance.ConclusionJKAP correlates with lower Th1 and Th17 cell percentages as well as milder disease severity.     

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.     

Clinical role of serum histone deacetylase 4 measurement in acute ischemic stroke: Relation to disease risk,severity, and prognosis

ObjectiveHistone deacetylase 4 (HDAC4) is engaged in the pathophysiology of acute ischemic stroke (AIS) through modulating atherosclerosis, inflammation and neurocyte death. This study aimed to investigate the clinical role of HDAC4 in AIS.MethodsSerum samples were collected from 176 AIS patients and 80 controls for HDAC4 detection by enzyme‐linked immunosorbent assay (ELISA). In AIS patients, disease severity was assessed by National Institute of Health Stroke Scale (NIHSS) score and their recurrence‐free survival (RFS) and overall survival (OS) were calculated, inflammatory cytokines and adhesion molecules were detected by ELISA.ResultsHDAC4 was declined in AIS patients vs. controls (p < 0.001), it also had certain ability of distinguishing AIS patients from controls with an area under curve of 0.748 (95% confidence interval: 0.689–0.806). Among AIS patients, HDAC4 was negatively linked with NIHSS score (p < 0.001) but no other clinical features (all p > 0.05). Moreover, HDAC4 was negatively related to interleukin (IL)‐17 (p = 0.010) and tumor necrosis factor alpha (p = 0.001), while it was not correlated with IL‐1β (p = 0.081) or IL‐6 (p = 0.074). Furthermore, HDAC4 was negatively associated with intercellular cell adhesion molecule‐1 (p < 0.001) and vascular cell adhesion molecule‐1 (p = 0.003). During a median follow‐up of 19.0 months, 17 (9.7%) patients had recurrence and 10 (5.7%) patients died. Additionally, high HDAC4 was linked with prolonged RFS (p = 0.044) but not OS (p = 0.079).ConclusionHDAC4 possesses the potential to monitor disease risk, inflammation and estimate recurrence of AIS, while further study with larger scale is needed to verify our findings.     

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.     

In‐hospital mortality in SARS‐CoV‐2 stratified by gamma‐glutamyl transferase levels

BackgroundThis study investigates in‐hospital mortality amongst patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and its relation to serum levels of gamma‐glutamyl transferase (GGT).MethodsPatients were stratified according to serum levels of gamma‐glutamyl transferase (GGT) (GGT<50 IU/L or GGT≥50 IU/L).ResultsA total of 802 participants were considered, amongst whom 486 had GGT<50 IU/L and a mean age of 48.1 (16.5) years, whilst 316 had GGT≥50 IU/L and a mean age of 53.8 (14.7) years. The chief sources of SARS‐CoV‐2 transmission were contact (366, 45.7%) and community (320, 40%). Most patients with GGT≥50 IU/L had either pneumonia (247, 78.2%) or acute respiratory distress syndrome (ARDS) (85, 26.9%), whilst those with GGT<50 IU/L had hypertension (141, 29%) or diabetes mellitus (DM) (147, 30.2%). Mortality was higher amongst patients with GGT≥50 IU/L (54, 17.1%) than amongst those with GGT<50 IU/L (29, 5.9%). More patients with GGT≥50 required high (83, 27.6%) or low (104, 34.6%) levels of oxygen, whereas most of those with GGT<50 had no requirement of oxygen (306, 71.2%). Multivariable logistic regression analysis indicated that GGT≥50 IU/L (odds ratio [OR]: 2.02, 95% confidence interval [CI]: 1.20–3.45, p=0.009), age (OR: 1.05, 95% CI: 1.03–1.07, p<0.001), hypertension (OR: 2.06, 95% CI: 1.19–3.63, p=0.011), methylprednisolone (OR: 2.96, 95% CI: 1.74–5.01, p<0.001) and fever (OR: 2.03, 95% CI: 1.15–3.68, p=0.016) were significant predictors of all‐cause cumulative mortality. A Cox proportional hazards regression model (B = −0.68, SE =0.24, HR =0.51, p = 0.004) showed that patients with GGT<50 IU/L had a 0.51‐times lower risk of all‐cause cumulative mortality than patients with GGT≥50 IU/L.ConclusionHigher levels of serum GGT were found to be an independent predictor of in‐hospital mortality.     

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.     

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.     

Prognostic value of glucose‐to‐lymphocyte ratio in critically ill patients with acute respiratory distress syndrome: A retrospective cohort study

BackgroundThere is need to identify biomarkers for prognosis of acute respiratory distress syndrome (ADRS). This may allow early and accurate identification of patients with high‐risk ARDS to guide adjustment of clinical treatment and nursing intervention, which would ultimately improve prognosis of patients with ARDS. Biomarkers based on a combination of fasting glucose and lymphocyte counts to predict prognosis in critically ill patients with ARDS remain undefined. In this study, we investigated the association between glucose‐to‐lymphocyte ratio (GLR) and in‐hospital mortality.MethodsThe study obtained data from Medical Information Mart for Intensive Care‐IV (MIMIC‐IV Version 1.0) database. We defined the GLR as fasting glucose/lymphocyte count and the patient in‐hospital mortality was considered as the outcome. In addition, we employed linear and logistic regression models for analysis.ResultsIn total, 1,085 patients with ARDS were included in this study. The eligible participants included 498 female and 587 males, with a mean age of 64.2 ± 17.5 years. Logistic regression analysis demonstrated that higher GLR was an independent risk factor for all‐cause mortality (OR =1.67, 95% CI: 1.26–2.22) after adjusting for age, sex, anion gap, white blood cell count, congestive heart failure, sequential organ failure assessment (SOFA), SBP, DBP, and respiratory rate in both the dichotomized group and subgroups. We also analyzed the in‐hospital mortality to ROC curves by comparing the value between SOFA + GLR and SOFA. The area under the curve (AUC) was 0.6991 for the SOFA + GLR (95% CI: 0.6634–0.7348), and 0.6613 for the SOFA (95% CI: 0.6238–0.6988).ConclusionOur data showed that the GLR was an independent predictor of in‐hospital mortality for patients with ARDS. The GLR is an integrated, readily available clinical biomarker for mortality in patients with ARDS.     

Association of B‐cell lymphoma 2/microRNA‐497 gene expression ratio score with metastasis in patients with colorectal cancer: A propensity‐matched cohort analysis

BackgroundDeregulated microRNAs (miRs) significantly impact cancer development and progression. Our in silico analysis revealed that miR‐497 and its target gene B‐cell lymphoma‐2 (BCL2) could be related to poor cancer outcomes.PurposeTo investigate the BCL2/miRNA‐497 expression ratio in colorectal cancer (CRC) and explore its association with the clinicopathological characteristics and CRC prognosis.MethodsArchived samples from 106 CRC patients were enrolled. MiR‐497 and BCL2 gene expressions were detected by Taq‐Man Real‐Time quantitative polymerase chain reaction in propensity‐matched metastatic and nonmetastatic cohorts after elimination of confounder bias.ResultsB‐cell lymphoma‐2 gene was upregulated in metastatic samples (median = 1.16, 95%CI = 1.09–1.60) compared to nonmetastatic (median = 1.02, 95%CI = 0.89–1.25, p < 0.001). In contrast, lower levels of miR‐495 were detected in specimens with distant metastasis (median = 0.05, 95%CI = 0.04–0.20) than nonmetastatic samples (median = 0.54, 95%CI = 0.47–0.58, p < 0.001). Estimated BCL2/miR‐497 ratio yielded a significant differential expression between the two cohort groups. Higher scores were observed in metastasis group (median = 1.39, 95%CI = 0.9–1.51) than nonmetastatic patients (median = 0.29, 95%CI = 0.19–0.39, p < 0.001). Receiver operating characteristic curve analysis showed BCL2/miR‐497 ratio score to have the highest predictive accuracy for metastasis at presentation. The area under the curve was 0.90 (95%CI = 0.839–0.964, p < 0.001) at cut‐off of >0.525, with high sensitivity 81.1% (95%CI = 68.6%–89.4%) and specificity 92.5% (95%CI = 82.1%–97.0%). Also, the ratio score was negatively correlated with disease‐free survival (r = −0.676, p < 0.001) and overall survival times (r = −0.650, p < 0.001). Kaplan–Meier curves showed lower survival rates in cohorts with high‐score compared to low‐score patients.ConclusionThe BCL2/miR497 expression ratio is associated with poor CRC prognosis in terms of metastasis and short survival.     

Longitudinal change of serum inter‐alpha‐trypsin inhibitor heavy chain H4, and its correlation with inflammation,multiorgan injury,and death risk in sepsis

BackgroundInter‐alpha‐trypsin inhibitor heavy chain H4 (ITIH4) inhibits infection‐induced inflammation and multiorgan injury through several methods. The present study aimed to estimate the association of serum ITIH4 with inflammatory cytokines, multiorgan injury, and death risk in sepsis patients.MethodsSerum samples were collected to detect ITIH4 by enzyme‐linked immunosorbent assay in 127 sepsis patients at admission (baseline), day (D)1, D3, and D7 after admission, as well as in 30 healthy controls (HCs). Additionally, 28‐day mortality was recorded in sepsis patients.ResultsITIH4 was reduced in sepsis patients versus HCs (median [interquartile range]: 147.9 [78.2–208.8] vs. 318.8 [237.2–511.4] ng/ml) (p < 0.001). In sepsis patients, ITIH4 was associated with the absence of cardiovascular and cerebrovascular disease history (p = 0.021). Additionally, ITIH4 was negatively correlated with tumor necrosis factor‐α (p < 0.001), interleukin (IL)‐1β (p < 0.001), IL‐6 (p = 0.019), IL‐17A (p = 0.002), and C‐reactive protein (p = 0.001), but positively related to IL‐10 (p = 0.007). Moreover, ITIH4 was also inversely associated with Acute Physiology and Chronic Health Evaluation II score (p = 0.002), Sequential Organ Failure Assessment (SOFA) score (p < 0.001), SOFA‐respiratory system score (p = 0.023), and SOFA‐renal system score (p = 0.007). Interestingly, ITIH4 gradually increased from baseline to D7 (p < 0.001); besides, ITIH4 at baseline (p = 0.009), D1 (p = 0.002), D3 (p < 0.001), and D7 (p = 0.015) were all decreased in sepsis deaths versus sepsis survivors.ConclusionSerum ITIH4 is raised from baseline to D7 after disease onset, and it reflects the reduction of systemic inflammation, disease severity, and 28‐day mortality for sepsis. However, further verification is required.     

LncRNA GAS5 relates to Th17 cells and serves as a potential biomarker for sepsis inflammation,organ dysfunctions and mortality risk

BackgroundLong noncoding RNA GAS5 (lnc‐GAS5) is able to regulate macrophage M1 polarization and Th17 cell differentiation, also engaged in sepsis‐induced inflammation and organ injury. This study aimed to further evaluate its linkage with Th1 cells and Th17 cells, as well as its clinical value in sepsis management.MethodsAbout 101 sepsis patients were enrolled followed by peripheral blood mononuclear cell (PBMC) and serum samples collection. PBMC lnc‐GAS5 was detected by RT‐qPCR; Th1 cells and Th17 cells in PBMC CD4⁺ T cells were detected by flow cytometry; serum IFN‐γ and IL‐17A were detected by ELISA. Besides, PBMC lnc‐GAS5 was also detected in 50 health controls (HCs).ResultsLnc‐GAS5 was reduced in sepsis patients than in HCs (p < 0.001), which also well‐distinguished sepsis patients from HCs with AUC 0.860. Lnc‐GAS5 did not relate to Th1 cells (p = 0.059) or IFN‐γ (p = 0.192); while negatively linked with Th17 cells (p = 0.002) and IL‐17A (p = 0.019) in sepsis patients. Interestingly, lnc‐GAS5 negatively correlated with SOFA score (p = 0.001), SOFA‐Respiratory system score (p = 0.001), SOFA‐Coagulation score (p = 0.015), and SOFA‐Renal system score (p = 0.026), but not SOFA‐Liver score (p = 0.080), SOFA‐Cardiovascular system score (p = 0.207) or SOFA‐Nervous system score (p = 0.182) in sepsis patients. Furthermore, lnc‐GAS5 was negatively related to CRP (p = 0.002) and APACHE II score (p = 0.004) in sepsis patients. Finally, lnc‐GAS5 was decreased in dead sepsis patients compared to survivors (p = 0.007), which also distinguished sepsis deaths from survivors with AUC 0.713.ConclusionLnc‐GAS5 relates to Th17 cells and serves as a potential biomarker for sepsis severity and mortality risk.     

Blood long non‐coding RNA intersectin 1–2 is highly expressed and links with increased Th17 cells,inflammation, multiple organ dysfunction,and mortality risk in sepsis patients

BackgroundLong non‐coding RNA intersectin 1–2 (lnc‐ITSN1‐2) exacerbates inflammation and promotes T‐helper (Th) cell differentiation, also serves as a biomarker in critical illness diseases. However, its clinical role in sepsis remains obscure. Hence, the study aimed to explore the relationship of lnc‐ITSN1‐2 with Th cells, inflammation, disease severity, multiple organ dysfunction, and mortality risk in sepsis.MethodsPeripheral blood mononuclear cells (PBMC) were isolated from 95 sepsis patients and 50 health controls, followed by lnc‐ITSN1‐2 evaluation using RT‐qPCR. PBMC Th1, Th17 cells and their secreted cytokines in serum were detected by flow cytometry and ELISA, respectively.ResultsLnc‐ITSN1‐2 in sepsis patients was higher than it in health controls (Z = −7.328, p < 0.001). Lnc‐ITSN1‐2 correlated with increased interferon‐gamma (p = 0.009), Th17 cells (p = 0.022), and interleukin‐17A (p = 0.006), but not Th1 cells (p = 0.169) in sepsis patients. Moreover, lnc‐ITSN1‐2 had a positive connection with C‐reactive protein (p = 0.001), acute pathologic and chronic health evaluation (APACHE) II (p = 0.024), and sequential organ failure assessment (SOFA) scores (p = 0.022). Regarding SOFA subscales, lnc‐ITSN1‐2 linked with elevated respiratory system score (p = 0.005), cardiovascular system score (p = 0.007), and renal system score (p = 0.004) but no other subscales. Besides, lnc‐ITSN1‐2 had an increasing trend, but no statistical difference, in septic deaths compared to survivors (Z = −1.852, p = 0.064).ConclusionLnc‐ITSN1‐2 reflects sepsis progression and unfavorable prognosis to some extent, which may serve as a potential biomarker to improve the management of sepsis patients.     

Analysis of anti‐apoptotic PVT1 oncogene and apoptosis‐related proteins (p53, Bcl2, PD‐1, and PD‐L1) expression in thyroid carcinoma

BackgroundAn aberrant expression of long non‐coding RNA PVT1 has been associated with apoptosis in various cancer types. We aimed to explore the PVT1 and four apoptosis‐related proteins (p53, Bcl2, and PD‐1/PD‐L1) signature in thyroid cancer (TC).MethodsThe PVT1 expression level was measured in 64 FFPE TC paired samples by real‐time quantitative PCR. Overall and stratified analyses by different clinicopathological features were done. The apoptotic proteins were evaluated by immunohistochemistry staining.ResultsOverall analysis showed significant PVT1upregulation in TC tissues (p < 0.001). Similarly, subgroup analysis by BRAF ^V600E mutation showed consistent results. Lower expression of p53 was associated with mortality (p = 0.001). Bcl2 overexpression was associated with greater tumor size (p = 0.005). At the same time, HCV‐positive cases were associated with repressed Bcl2 expression levels (54.3% in HCV‐negative vs. 6.9% in HCV‐positive cases, p = 0.011). PD‐1 expression was associated with lymph node metastasis (p = 0.004). Enhanced PD‐L1 expression in the tumor was associated with a higher tumor stage, lymphovascular invasion, and mortality risk. Kaplan–Meier curves for overall survival showed that low p53 and high PD‐L1 expressions were associated with lower survival time. The p53‐positive staining is associated with a 90% decreased mortality risk (HR = 0.10, 95%CI = 0.02–0.47, p = 0.001), while patients with high PD‐L1 were five times more likely to die (HR = 4.74, 95%CI = 1.2–18.7, p = 0.027).ConclusionOur results confirm the upregulation of PVT1 in TC. The apoptosis‐related proteins (p53, Bcl2, and PD‐1/PD‐L1) showed different prognostic utility in TC patients; in particular, low p53 and high PD‐L1 expressions associated with low survival times. Further large‐scale and mechanistic studies are warranted.     

Th1, Th2, and Th17 cells are dysregulated,but only Th17 cells relate to C‐reactive protein,D‐dimer,and mortality risk in Stanford type A aortic dissection patients

BackgroundT helper (Th) cells are closely involved in vascular inflammation, endothelial dysfunction, and atherogenesis, which are the hallmarks of aortic dissection (AD). This study aimed to evaluate the clinical value of Th1, Th2, and Th17 cell measurements in Stanford type A AD patients.MethodsStanford type A AD patients (N=80) and non‐AD patients with chest pain (N = 40) were recruited. Then, Th1, Th2, and Th17 cells in peripheral blood CD4⁺ T cells from all participants were detected by flow cytometry. The 30‐day mortality of Stanford type A AD patients was recorded.ResultsTh1 and Th17 cells were higher, while Th2 cells were lower in Stanford type A AD patients compared with non‐AD patients (all p < 0.001). Meanwhile, Th1 cells (area under curve (AUC): 0.734, 95% confidence interval (CI): 0.640–0.828), Th2 cells (AUC: 0.841, 95% CI: 0.756–0.925), and Th17 cells (AUC: 0.898, 95% CI: 0.839–0.957) could distinguish Stanford type A patients from non‐AD patients. Moreover, Th1 cells (p = 0.037) and Th17 cells (p = 0.001) were positively related to CRP, and Th17 cells (p = 0.039) were also positively associated with D‐dimer in Stanford type A AD patients. Furthermore, Th17 cells were elevated in deaths compared with survivors (p = 0.001), also, it could estimate 30‐day mortality risk in Stanford type A AD patients with an AUC of 0.741 (95% CI: 0.614–0.867), which was similar to the value of CRP (AUC: 0.771, 95% CI: 0.660–0.882), but lower than the value of D‐dimer (AUC: 0.818, 95% CI: 0.722–0.913).ConclusionTh1, Th2, and Th17 cells are dysregulated, but only the Th17 cells relate to CRP, D‐dimer, and 30‐day mortality risk in Stanford type A AD patients.