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1.
BackgroundBreast cancer is a frequently occurring malignant tumor in women. Angiotensin‐converting enzyme 2 (ACE2) is widely expressed in most organs; however, the association of ACE2 with prognosis and immune infiltration in breast invasive carcinoma (BRCA) remains elusive.MethodsWe explored the expression level and prognostic value of ACE2 in patients with BRCA using a series of online bioinformatics analysis databases encompassing Oncomine, UALCAN, Kaplan–Meier plotter, TIMER, LinkedOmics, and GEO. qRT‐PCR was performed to verify our findings.ResultsAngiotensin‐converting enzyme 2 mRNA and protein expression levels were decreased in BRCA tissues, and patients with low ACE2 expression levels had a poor prognosis. DNA promoter methylation of ACE2 significantly downregulated ACE2 expression in BRCA, while the expression of this protein was positively linked to immune infiltration of B cells, CD8+ and CD4+ T cells, neutrophils, and dendritic cells in BRCA tissues. The high expression level of ACE2 in enriched basophils, CD8+ T cells, and type‐2 helper T cells, which showed decreasing levels, indicated a better prognosis for BRCA. Enrichment analyses revealed that NF‐κB, IL‐17, and TNF signaling pathways were highly correlated to ACE2 in BRCA. Verification study revealed that downregulation of ACE2 was associated with a better prognosis in BRCA. Univariate and multivariate analysis confirmed ACE2 expression and clinical stage as independent prognostic factors for breast cancer.ConclusionsAngiotensin‐converting enzyme 2 may be a potential prognostic biomarker and target for BRCA. Nevertheless, future investigations are needed for validating our findings and promoting the clinical application of ACE2 in BRCA.  相似文献   

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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 (= 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.  相似文献   

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BackgroundImmunotherapy was widely used for the treatment of non‐small cell lung cancer (NSCLC). However, whether inhibition of immune checkpoints individually or simultaneously could improve the therapeutic efficacy of NSCLC remains to be investigated. Here, we explored the aberrant levels of several checkpoints and evaluated their potential diagnostic values for NSCLC.MethodsSerum samples of 89 NSCLC patients and 57 healthy donors were collected from Nanjing Drum Tower Hospital between November 2019 and July 2020. Fourteen human immune checkpoints were quantified by Procarta‐Plex Human Immuno‐Oncology Checkpoint Panel.ResultsThe expression levels of sTIM‐3, sCD137, sCD27, sLAG‐3, sIDO, sPD‐L2, sCD152, sCD80, and sPD‐1 were all significantly increased in serum of NSCLC patients. Especially, sLAG‐3 was significantly elevated in serum of NSCLC patients at early‐stage (stages I and II), TIM‐3, CD137, and CD27 were significantly higher in the advanced NSCLC patients (stages III and IV) than in the early‐stage groups. Receiver operating characteristics (ROC) results showed that except for PD‐1, all the other immune checkpoint proteins had potential diagnostic values for NSCLC. sTIM‐3 had the highest diagnostic accuracy, followed by sLAG‐3. Combining sTIM‐3, sLAG‐3, and sCD137 could increase the accuracy to a higher level. Moreover, sCD27 was correlated with NSCLC cancer type, age, sex, and disease stage, while sCD137 was correlated with age and disease stage. sTIM‐3 and sIDO were correlated with stage and age, respectively.ConclusionsTIM‐3 and LAG‐3 were independent biomarkers for the early diagnosis of NSCLC. The combination of TIM‐3, LAG‐3, and CD137 could increase the diagnostic accuracy.  相似文献   

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BackgroundThere is still a lack of tools to assess the prognosis of ischemic stroke patients induced by hypertension. In this study, we built a novel prognostic assessment model for ischemic stroke in the Chinese hypertensive population.MethodsMass spectrometry technique was used to analyze the changes in serum protein profiles of hypertensive patients with ischemic stroke. A total of 314 hypertensive patients were divided into the testing group (206 patients) and the validation group (108 patients).ResultsCompared with hypertensive patients without ischemic stroke, serum cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4), ischemia‐modified albumin (IMA), lipoprotein‐associated phospholipase A2 (Lp‐PLA2), glial fibrillary acidic protein (GFAP), and homocysteine (HCY) levels were significantly increased among hypertensive patients with ischemic stroke (p < 0.05). Then, we built a novel prognostic assessment model for hypertensive patients with ischemic stroke [Logit(P) = 29.172–1.088*CTLA‐4–0.952*IMA‐0.537*Lp‐PLA2 −0.066*GFAP −0.149*HCY]. It showed higher efficiency (AUC = 0.981, sensitivity = 95.5%, specificity = 93.8%) than any single marker. The estimated probability was 0.739, which means if higher than 0.739, it was classified into poor prognosis. Compared with the estimated probability ≤0.739 group, the survival rate of hypertensive patients with ischemic stroke in the estimated probability >0.739 group was significantly decreased (χ 2 = 40.001, p < 0.001). In the validation group, our novel prognostic assessment model still showed good efficiency (AUC = 0.969, sensitivity = 89.4%, specificity = 92.5%; χ 2 = 47.551, p < 0.001).ConclusionCurrent novel prognostic assessment model we have built is of great value in the prognostic evaluation for ischemic stroke in the Chinese hypertensive population.  相似文献   

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Celiac disease (CD) is a chronic autoimmune disorder of small intestine against dietary gluten, among genetically predisposed individuals. Monocytes are versatile innate immune cells involved in the regulation of inflammation, and strongly involved in the intestinal immunity. However, the role of monocytes and their subtypes in CD is not well demonstrated.MethodsHere, we assessed the polarization of CD14+ monocytes by evaluating the M1 (CD16) and M2 (CD163) markers by flowcytometry, their soluble forms (sCD16 and sCD163), and the serum levels of IL‐10, IL‐12, TGF‐β, and TNF‐α cytokines using ELISA method, among 30 CD patients and 30 sex‐ and age‐matched healthy subjects (HS). We also analyzed the diagnostic values of all variables with significant differences.ResultsCD14+CD163+ monocytes were more frequent in CD patients than HS, while CD14+CD16+ monocytes were higher in HS. IL‐10and TNF‐α increased, and TGF‐β expression was decreased among CD patients. The sCD16 serum levels were elevated in patients, while sCD163 was higher but not significant among CD patients. CD163+/CD16+ and IL‐10/IL‐12 ratios were higher in CD patients, and TGFβ/TNFα ratio was higher in HS group. IL‐10, CD14+CD163+, TNF‐α, and IL‐10/IL‐12 ratios with the AUC over 0.7 were introduced as fair diagnostic markers. Our findings revealed that the M2 (CD14+CD163+) monocytes were more frequent among CD patients, and the cytokine balance was disturbed.ConclusionAccording to the significant functional diversities of monocyte subtypes between CD patients and HS group, these immunologic markers could be introduced as specific diagnostic biomarkers for CD.  相似文献   

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Background Mycoplasma pneumoniae (MP) is a common pathogen of community‐acquired pneumonia in children. In the present study, serum amyloid A (SAA), C‐reactive protein (CRP), and procalcitonin (PCT) levels in children with MP infection were analyzed and the differential diagnoses of MP evaluated.MethodsThe study included 152 children with MP infection hospitalized in Tai’an Central Hospital in Shandong Province and 50 healthy children as controls. SAA, CRP, and PCT, as well as serum immunoglobulins and T lymphocyte subsets were analyzed during the acute and convalescent phases. Among the MP‐infected children, 30 cases were selected to monitor the SAA, immunoglobulins, and T lymphocyte subset levels for a week.ResultsThe SAA, CRP, PCT, IgA, and IgM levels were significantly higher in the MP‐infected group than in the control group (F (SAA) = 83.91, p < 0.05; F (CRP) = 40.79, p < 0.05; F (PCT) = 60.58, p < 0.05; F (IgA) = 43.45, p < 0.05; F (IgM) = 233.88, p < 0.05). In addition, the levels of these factors were significantly higher in the acute phase than in the convalescent phase (p < 0.05). However, significant difference was not observed in the IgG level between these two groups (p > 0.05). The CD3+ and CD4+ levels in the MP‐infected group were lower than in the control group ( F (CD3+)= 60.58, P < 0.05; F (CD4+) = 89.05, p < 0.05), and the CD8+ level was higher than in the control group ( F (CD8+)= 96.96, p < 0.05). The CD3+, CD4+, and CD8+ levels were significantly different between the acute phase and the convalescent phase (CD3+: acute phase vs. convalescent phase, q = 2.79, p < 0.05; CD4+: acute phase vs. convalescent phase, q = 2.83, p < 0.05; CD8+: acute phase vs. convalescent phase, q = 3.15, p < 0.05). The changes in serum SAA levels in the MP‐infected group positively correlated with the changes in IgA, IgM, and CD8+ levels and negatively correlated with CD3+, CD4+, and CD4+/CD8+.ConclusionSAA, CRP, and PCT were specific markers for diagnosing early MP infection in children. These findings are important in the differential diagnosis of MP infection and clinical guidance for MP treatment.  相似文献   

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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.  相似文献   

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BackgroundThere are no validated biomarkers that can predict the clinical benefit of immune checkpoint blockers against the programmed cell death protein 1 (PD‐1) treatments in hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic value of inflammation‐immunity‐nutrition score (IINS) in patients with HCC treated with anti‐PD‐1 therapy.MethodsA consecutive series of 101 HCC patients treated with PD‐1 inhibitors in Sichuan Provincial People''s Hospital between January 2018 and August 2020 were enrolled in the retrospective study. IINS (0–6) was constructed based on pretreatment high‐sensitivity C‐reactive protein (hsCRP), lymphocyte (LYM), and albumin (ALB). The patients were divided into high and low IINS groups according to IINS values. Prognostic values of each variable were evaluated with univariate and multivariate time‐dependent Cox regression analyses. Survival curves were calculated and compared using the Kaplan–Meier method and log‐rank test. The prognostic performance of IINS was further compared with that of other traditional prognostic indicators by receiver operating characteristic (ROC) curve and the areas under the ROC curve.ResultsPatients with low IINS had longer overall survival (OS) (HR: 4.711, 95% CI: 1.80–12.37, p = .001) and progression‐free survival (HR: 3.411, 95% CI: 1.79–6.51, p < .0001) than those with high IINS. The multivariate analysis identified IINS (HR: 3.746, 95% CI: 1.05–13.38, p = .042) and tumor number (HR: 5.111, 95% CI: 1.075–24.299, p = .04) as independent prognostic factors. According to ROC analysis, IINS (AUC =0.729, 95% CI: 0.597–0.861, p = .002) presented better prognostic performance than other traditional prognostic indicators. The area of the IINS‐CA19‐9 under the ROC curve (AUC) was higher than that of the IINS or CA19‐9 levels for the prediction of OS.ConclusionThe results suggest that IINS may be an independent prognostic indicator for HCC patients treated with anti‐PD‐1 therapy. IINS‐CA19‐9 classification may be more effective in predicting clinical benefit of anti‐PD‐1 therapy in HCC patients.  相似文献   

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The serum Chitinase 3‐like protein 1 (CHI3L1) protein level can distinguish the stages of liver fibrosis to a great extent. However, the diagnostic and prognostic significance of serum CHI3L1 in hepatocellular carcinoma (HCC) is not clarified. To evaluate the diagnostic and prognostic value of CHI3L1 in HCC, a total of 128 HCC patients treated in the HwaMei Hospital, University of Chinese Academy of Sciences, from December 2018 to April 2020 were collected retrospectively. Matched age and gender subjects, 40 patients with liver cirrhosis, 40 patients with chronic hepatitis, and 40 healthy subjects were enrolled in the control group. The relevant clinical laboratory and examination data and the overall survival time (OS) of the HCC patients were collected. The serum CHI3L1 expression level is related to α‐fetoprotein (AFP), tumor‐node‐metastasis (TNM) stage, maximum tumor diameter, liver cirrhosis, and HCC patient''s OS (p < 0.05). The area under the curve (AUC) of CHI3L1 was 0.7875 with the cutoff value of 91.36 ng/ml. Combining the serum CHI3L1 and α‐fetoprotein (AFP) by a binary logistic regression model can increase the diagnostic sensitivity to 97.5%. Multivariate Cox regression analysis indicated that CHI3L1 is an independent prognostic factor in patients with HCC.  相似文献   

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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.  相似文献   

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BackgroundPlatelet transfusion refractoriness (PTR) remains a difficult problem in patients requiring long‐term platelet supportive care. However, there are little data on the frequency of platelet antibodies in multiply transfused Chinese patients. Moreover, the relationship between peripheral regulatory T cells (Tregs) and PTR remains unclear.MethodsWe retrospectively studied the frequency of alloimmunization against platelet antigens in patients receiving multiple transfusions between 2013 and 2017. Monoclonal antibody solid‐phase platelet antibody test (MASPAT) kits were used to screen for platelet antibodies before each platelet transfusion. Peripheral Tregs and CD4+CD25+CD127 T cells were detected by flow cytometry, while transforming growth factor‐beta (TGF‐β) and interleukin (IL)‐17 cytokines were detected by enzyme‐linked immunosorbent assay.ResultsA total of 399 patients who met the inclusion criteria were enrolled for the analysis of platelet antibodies and refractoriness. Among these patients, 10 (2.5%) were positive for platelet antibodies before transfusion and 47 (11.8%) became antibody‐positive during the study period. The number of alloimmunized patients was significantly higher in patients with hematological disease as compared with other disease groups (< 0.05). Refractoriness and alloimmunization occurred in 77 (19.3%) and 22 (28.6%) patients, respectively. There were no significant differences in CD4+, CD8+, and CD4+CD25+CD127 T cell numbers and plasma levels of TGF‐β1 and IL‐17 between patients with PTR and the control group.ConclusionsRefractoriness was common in patients undergoing multiple platelet transfusions (19.3%), with alloimmunization observed in 28.6% of patients. However, Tregs in peripheral blood may not play a key role in PTR.  相似文献   

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BackgroundSerum potassium disorders are commonly seen in patients with advanced cirrhosis and have a detrimental effect on clinical outcome, but its role in HBV‐related decompensated cirrhosis (DeCi) is remained to be illustrated. We aim to assess the effects of serum potassium on outcomes in HBV‐DeCi patients.MethodsRetrospective study included 155 subjects. Multivariate analysis was used to determine the independent prognostic factor. Predictive ability of mortality for variables was determined using the receiver operating characteristics curves.ResultsThe 30‐day in‐hospital mortality was 12.9%. Serum potassium levels differed markedly between survivors and non‐survivors. On multivariate analysis, Model for End‐Stage Liver Disease (MELD) score and serum potassium level were identified as independent predictors of outcomes in HBV‐DeCi patients. The combination of serum potassium and MELD score could improve prognostic accuracy in these patients.ConclusionsOur findings suggest that serum potassium is an effective predictor for poor outcomes in HBV‐DeCi patients.  相似文献   

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BackgroundLong non‐coding RNAs (LncRNAs) are considered as potential diagnostic markers for a variety of tumors. Here, we aimed to explore the changes of LINC00941 and LINC00514 expression in hepatitis B virus (HBV) infection‐related liver disease and evaluate their application value in disease diagnosis.MethodsSerum levels of LINC00941 and LINC00514 were detected by qRT‐PCR. Potential diagnostic values were evaluated by receiver operating characteristic curve (ROC) analysis.ResultsSerum LINC00941 and LINC00514 levels were elevated in patients with chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) compared with controls. When distinguishing HCC from controls, serum LINC00941 and LINC00514 had diagnostic parameters of an AUC of 0.919 and 0.808, sensitivity of 85% and 90%, and specificity of 86.67% and 56.67%, which were higher than parameters for alpha fetal protein (AFP) (all < 0.0001). When distinguishing HCC from LC, CHB, or LC from controls, the combined detection of LINC00941 or LINC00514 can significantly improve the accuracy of AFP test alone (all < 0.05).ConclusionsLINC00941 and LINC00514 were increased in the serum of HBV infection‐associated liver diseases and might be independent markers for the detection of liver diseases.  相似文献   

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ObjectiveThe current study aimed to investigate the prognostic value of T helper (Th) 1 and Th17 proportions in sepsis patients.MethodsTh1 and Th17 cells in blood CD4+ T cells were detected by flow cytometry in 210 sepsis patients and 100 healthy controls (HCs). Besides, serum interferon‐γ (IFN‐γ), tumor necrosis factor‐α (TNF‐α), and interleukin‐17 (IL‐17) levels in the enrolled sepsis patients were determined with enzyme‐linked immunosorbent assay.ResultsCompared with HCs, Th1 and Th17 proportions were elevated in sepsis patients (both p < .001). Meanwhile, Th1 proportion was strongly correlated with IFN‐γ (p < .001, r = .484) but weakly correlated with TNF‐α (p = .024, r = .156) and IL‐17 (p = .002, r = .212), while Th17 proportion showed faint correlation with IFN‐γ (p = .015, r = .168), but strong correlations with TNF‐α (p < .001, r = .602) and IL‐17 (p < .001, r = .498) in sepsis patients. Besides, Th1 proportion was weakly associated with APACHE II score (p = .030, r = .150), but Th17 proportion was closely associated with APACHE II score (p < .001, r = .322) and SOFA score (p < .001, r = .337) in sepsis patients. Regarding their prognostic value, Th1 proportion (p = .042) was slightly, while Th17 proportion (p < .001) was dramatically, increased in septic deaths compared with survivors, and Th17 possessed good predictive value for 28‐day mortality risk (AUC: 0.748, 95% CI: 0.659–0.836).ConclusionTh1 and Th17 proportions are elevated in sepsis patients compared with HCs, and Th17 proportion is correlated with increased disease severity, higher inflammation level, and worse prognosis in sepsis patients.  相似文献   

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AimsTo assess the relation of high serum OPG level and carotid atherosclerosis in maintenance hemodialysis (MHD) patients using low‐flux reused dialyzer.Materials and MethodsWe examined 209 MHD patients with and without carotid atherosclerosis (83 patients and 126 patients) to establish the relation between OPG and atherosclerosis.ResultsThe proportion of carotid atherosclerosis was 39.7%. The median serum OPG level was 45.3 pmol/L. Serum OPG had a good predicting value for atherosclerosis in MHD patients using low‐flux reused dialyzer (AUC = 0.934, p < 0.001, cutoff value = 43.35 pmol/L, Se = 81.3%, Sp = 90.9%).ConclusionsIn this study, serum OPG had a good predicting value for atherosclerosis in MHD patients using low‐flux reused dialyzer.  相似文献   

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BackgroundPlatelet index was reported to be used as a potential prognostic marker in patients with liver fibrosis. We aimed to explore the association between plateletcrit (PCT) and severity of hepatic sinusoidal obstruction syndrome (HSOS).MethodsSeventy consecutive patients who diagnosed as HSOS by CT and medical history during January 2017‐November 2021 were included. All patients were divided into two groups which confirmed as favorable prognosis and poor prognosis on the basis of Child‐Turcotte‐Pugh score system. The clinical manifestation and laboratory parameters of two groups were retrospectively selected. PCT was evaluated within two groups, and the diagnostic accuracy was evaluated by the area under the receiver operating characteristic curve.ResultsThe significant difference between the two groups not only in diarrhea, abdominal pain, abdominal distention, urine volume, and skin ecchymosis (< 0.005), but also in WBC count, NE count, PLT count, TBIL, and D‐Dimer (p < 0.005) were found. The PCT level was significantly higher in HSOS patients with poor prognosis (0.169 ± 0.060) than favorable prognosis patients (0.110 ± 0.047). The area under the receiver operating characteristic curve of RDW in predicting poor prognosis was 0.781, with 67.70% sensitivity and 79.5%specificity.ConclusionsThe PCT level was correlated positively with the poor prognosis in HSOS patients. PCT can be a promising indicator for predicting prognosis in HSOS  相似文献   

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