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Predictive value of serum epithelial cell homeostasis-signal transduction markers for clinically significant portal hypertension in patients with liver cirrhosis
Author:Predictive value of serum epithelial cell homeostasis-signal transduction markers for clinically significant portal hypertension in patients with liver cirrhosis
keyword:Liver cirrhosisPortal hypertensionClinically significant portal hypertensionCytokeratin 19 fragmentβ-Arrestin-2Signal transductionDiagnostic value
Objective To investigate the predictive value of serum epithelial cell homeostasis-signal transduction markers—cytokeratin 19 fragment(CYFRA21-1) and β-arrestin-2—for the development of clinically significant portal hypertension(CSPH) in patients with liver cirrhosis. Methods A total of 287 patients with liver cirrhosis admitted to the Department of Gastroenterology, Sinopharm Tongmei General Hospital from April 2021 to October 2025 were enrolled as the cirrhosis group, and 287 healthy individuals undergoing physical examinations at the same hospital during the same period were selected as the healthy control group. The cirrhosis group was further divided into a CSPH subgroup(80 cases) and a non-CSPH subgroup(207 cases) based on hepatic venous pressure gradient(HVPG) measurements. Serum levels of CYFRA21-1 andβ-arrestin-2 were measured using enzyme-linked immunosorbent assay. Pearson correlation analysis was performed to assess the correlation between CYFRA21-1, β-arrestin-2, and HVPG values. Multivariate logistic regression analysis was used to identify risk factors for CSPH in patients with liver cirrhosis. Receiver operating characteristic(ROC) curves were applied to evaluate the value of CYFRA21-1 and β-arrestin-2 in predicting CSPH in cirrhotic patients. Results Serum levels of CYFRA21-1 and β-arrestin-2 in the cirrhosis group were significantly higher than those in the healthy control group(t =23.097, 26.485; both P <0.001). Serum levels of CYFRA21-1 and β-arrestin-2 in the CSPH subgroup were significantly higher than those in the non-CSPH subgroup(t = 13.927, 10.981; both P <0.001). Serum CYFRA21-1 and β-arrestin-2 levels were positively correlated with HVPG values(r = 0.615, 0.553; both P <0.001). The proportions of esophagogastric varices, ChildPugh grade C, liver stiffness measurement, FIB-4 index, and INR in the CSPH subgroup were significantly higher than those in the non-CSPH subgroup, while albumin and platelet counts were significantly lower(χ2/t = 22.182, 26.093, 22.177, 14.979,12.222, 11.280, 18.463; all P <0.001). High CYFRA21-1, high β-arrestin-2, and high liver stiffness measurement were independent risk factors for CSPH in patients with cirrhosis, while high platelet count was an independent protective factor [OR(95%CI) = 1.844(1.286-2.645), 2.450(1.498-4.008), 1.203(1.087-1.332), 0.972(0.955-0.990)]. The AUCs of serum CYFRA21-1, β-arrestin-2, and their combination for diagnosing CSPH in patients with cirrhosis were 0.794, 0.799, and 0.884,respectively. The combined diagnosis showed significantly higher AUC than either single marker(Z = 3.738, 2.713; P <0.001,0.006). Conclusion Serum levels of CYFRA21-1 and β-arrestin-2 are significantly elevated in patients with liver cirrhosis and are closely associated with HVPG and the development of CSPH. Combined detection of these two markers demonstrates high predictive value for CSPH in cirrhotic patients.
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The relationship between serum KL-6 and TRAP1 levels and clinical stage and prognosis in patients with primary liver cancer
Author:Zheng Qianqian Lei Wei Jiang Shan Tian Boyan
keyword:Primary liver cancerKrebs von den Lungen-6Tumor necrosis factor receptor-associated protein 1Clinical stagePrognosis
Objective To investigate the changes in serum Krebs von den Lungen-6(KL-6) and tumor necrosis factor receptor-associated protein 1(TRAP1) levels in patients with primary liver cancer(PLC) and their relationships with clinical stage and prognosis. Methods A total of 135 patients with PLC admitted to our hospital from August 2021 to August 2023 were enrolled as the PLC group. Based on clinical staging criteria, patients were classified into stage Ⅰ(36 cases), stageⅡ(45 cases), stage Ⅲ(38 cases), and stage Ⅳ(16 cases). According to recurrence, metastasis, and survival status during follow-up, patients were further divided into a good prognosis group(83 cases) and a poor prognosis group(52 cases). Another120 healthy volunteers who underwent physical examinations during the same period were selected as the control group. Serum levels of KL-6 and TRAP1 were detected by ELISA. The Spearman method was used to analyze the correlation between serum KL-6, TRAP1 levels and clinical stage. Logistic regression analysis was performed to identify factors influencing poor prognosis in PLC patients. ROC and DCA curves were used to evaluate the predictive value of serum KL-6 and TRAP1 for poor prognosis. Relative risk(RR) analysis was conducted to explore the relationship between different serum levels of KL-6 and TRAP1 and poor prognosis. Results Serum KL-6 and TRAP1 levels in the PLC group were significantly higher than those in the control group(t = 14.500, 28.592; both P <0.05). As clinical stage increased, serum KL-6 and TRAP1 levels gradually increased(F = 22.194, 55.861; both P <0.05), and both were positively correlated with clinical stage(rs= 0.544, 0.734; both P <0.05). The poor prognosis subgroup had significantly higher proportions of patients with lymph node metastasis, tumor stage Ⅲ–Ⅳ, portal vein tumor thrombus, and elevated serum KL-6 and TRAP1 levels compared with the good prognosis subgroup(χ2/t = 12.622, 6.756, 6.204, 6.994, 6.206;P <0.001, 0.009, 0.013, <0.001, <0.001). Lymph node metastasis[OR(95%CI) = 1.528(1.108-2.107)], tumor stage Ⅲ–Ⅳ [OR(95%CI) = 1.329(1.061-1.665)], portal vein tumor thrombus [OR(95%CI) = 1.743(1.139-2.667)], high KL-6[OR(95%CI) = 2.046(1.246-3.359)], and high TRAP1 [OR(95%CI) = 1.835(1.491-2.259)] were independent risk factors for poor prognosis in PLC patients. The AUCs of serum KL-6, TRAP1, and their combination for predicting poor prognosis were 0.788, 0.789, and 0.896, respectively. The combined prediction showed significantly better performance than either marker alone(Z = 2.212, 2.155;P = 0.013, 0.031). DCA results indicated that within the high-risk threshold range of 0.10 – 0.92, the combined prediction provided greater net benefit than individual markers. RR analysis showed that PLC patients with serum KL-6 > 109.40 U/ml [RR(95%CI) = 3.375(2.093-5.442)] and TRAP1 >28.62 μg/L [RR(95%CI) = 4.400(2.246-8.620)]had a significantly higher risk of poor prognosis(both P <0.05). Conclusion Serum KL-6 and TRAP1 levels are elevated in PLC patients and are positively correlated with clinical stage. Both markers demonstrate good predictive value for patient prognosis.
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Correlation and predictive value of thyroid hormone sensitivity indices with carotid atherosclerotic plaque in elderly patients with H-type hypertension
Author:Jiang Lan Liu Zhen Ding Wei Peng Ying
keyword:H-type hypertensionCarotid atherosclerotic plaqueThyroid functionThyroid feedback quantile indexThyroid hormone resistance indexCorrelationElderly
Objective To investigate the relationship between thyroid hormone sensitivity and carotid atherosclerotic plaque in elderly patients with euthyroid H-type hypertension and to evaluate its predictive value. Methods A total of 155 elderly H-type hypertensive patients with normal thyroid function who attended the Department of Endocrinology, Anqing First People' s Hospital from June 2022 to June 2024 were selected as study subjects. According to the presence or absence of carotid atherosclerotic plaque, patients were divided into a plaque group(94 cases) and a non-plaque group(61 cases). Thyroid hormones were measured, and thyroid hormone sensitivity indices(TFQI, TSHI, TT4RI, TRI, FTFT, FT4/TSH) were calculated. Carotid atherosclerotic plaque parameters[carotid intima-media thickness(IMT), plaque number, and maximum plaque thickness]were assessed. The correlations between thyroid hormone sensitivity indices and carotid plaque parameters were analyzed using Spearman rank correlation. Multivariate logistic regression was used to analyze the influencing factors of carotid atherosclerotic plaque formation in elderly H-type hypertensive patients. ROC curves were used to evaluate the value of thyroid hormone sensitivity indices in predicting carotid atherosclerotic plaque formation. Results Age, blood pressure, Hcy,blood lipids, blood glucose, and levels of TSH, TFQI, TSHI, TT4 RI, and TRI in the plaque group were significantly higher than those in the non-plaque group, while BMI, FT3, FTFT, and FT4/TSH were significantly lower(t = 2.949, 4.567, 3.890,5.123, 4.231, 3.567, 4.123, 4.321, 5.678, 7.234, 8.123, 7.890, 6.123, 3.215, 4.890, 4.987, 3.567, 8.901;P =0.004, <0.001, 0.001, <0.001, 0.001, 0.001, 0.001, 0.001, <0.001, <0.001, <0.001, <0.001, <0.001, 0.002, <0.001, <0.001, 0.001, <0.001). TFQI,TSHI, TT4 RI, and TRI were positively correlated with IMT, plaque number, and maximum plaque thickness(r = 0.598, 0.521,0.556; r = 0.612, 0.543, 0.578; r = 0.576, 0.502, 0.534; r = 0.567, 0.489, 0.523, respectively; all P <0.001), while FTFT and FT4/TSH were negatively correlated with IMT, plaque number, and maximum plaque thickness(r =-0.489,-0.432,-0.467;r =-0.512,-0.456,-0.498, respectively; all P <0.001). Elevated TFQI and elevated TRI were independent risk factors for carotid atherosclerotic plaque formation [OR(95%CI) = 2.989(1.733-5.156), 2.677(1.586-4.518), respectively], while elevated HDL-C, elevated FTFT, and elevated FT4/TSH were independent protective factors [OR(95%CI) = 0.876(0.785-0.978), 0.444(0.225-0.875), 0.434(0.246-0.765), 0.435(0.263-0.719), respectively]. The AUCs of TFQI, TSHI, TT4 RI, FTFT, TRI, FT4/TSH, and their combination for predicting carotid atherosclerotic plaque formation were 0.836, 0.567, 0.543, 0.721, 0.756,0.732, and 0.892, respectively. The combined prediction model showed significantly superior predictive value compared to each individual indicator(DeLong test: Z = 2.913, 4.562, 4.987, 3.456, 3.123, 3.567; P = 0.004, <0.001, <0.001, 0.001, 0.002,0.001, respectively). Conclusion Reduced thyroid hormone sensitivity is closely associated with carotid atherosclerotic plaque. TFQI, TRI, FTFT, and FT4/TSH may serve as potential indicators for plaque risk assessment, with TFQI showing high predictive value.
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Clinicopathological analysis of thirteen cases of IgG4-related retroperitoneal fibrosis
Author:Liu Xuefei Hu Hao Li Yiming Shi Yuchuan Yin Lijuan He Miaoxia
keyword:IgG4-related retroperitoneal fibrosisIgG4-related diseaseFibrotic typeClinicopathological featuresDifferential diagnosis
Objective To investigate the clinical, imaging, and pathological features of IgG4-related retroperitoneal fibrosis(IgG4-RPF) and to improve diagnostic accuracy. Methods Clinical data, morphological, and immunohistochemical findings of 13 patients with pathologically confirmed IgG4-RPF from January 2021 to December 2025 were retrospectively analyzed. Results Among the 13 patients, 11 were male and 2 were female, with a median age of 60 years. Clinical manifestations were diverse, and 38.5%(5/13) were incidental findings on physical examination. Serum IgG4 was measured in 9 patients, and 5(55.6%) had levels >1.35 g/L. Imaging showed retroperitoneal soft-tissue masses in all cases, most encasing the abdominal aorta and/or iliac vessels. Pathologically, all cases exhibited dense lymphoplasmacytic infiltration; storiform fibrosis was present in 84.6%(11/13) and obliterative phlebitis in 38.5%(5/13). Immunohistochemically, all cases had > 10 IgG4+plasma cells per high-power field, and 76.9%(10/13) had an IgG4+/IgG+ratio >40%. Conclusion IgG4-RPF predominantly affects middle-aged and elderly males with insidious onset. Diagnosis requires comprehensive assessment of clinical features, imaging, serology, and pathology, with differential diagnosis from lymphoma and soft tissue tumors.
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The relationship between the expression of PRMT6 and UPP1 in non-muscle invasive bladder cancer and clinicopathological features and postoperative recurrence and metastasis
Author:Cao Jian Li Guangyao Geng Xinlong Gao Lu Han Pengfei
keyword:Non-muscle invasive bladder cancerProtein arginine methyltransferase 6Uridine phosphorylase 1PrognosisCorrelation
Objective To investigate the expression levels of protein arginine methyltransferase 6(PRMT6) and uridine phosphorylase 1(UPP1) in non-muscle invasive bladder cancer(NMIBC), and to analyze their relationship with clinicopathological features and the evaluation value of postoperative prognosis. Methods The clinical data of 134 patients with NMIBC who were treated in the Department of Urology, Linfen Central Hospital of Shanxi Province from February 2019 to February 2022 were collected(cancer tissue and paracancerous tissue samples of patients with pathologically confirmed NMIBC). The expression levels of PRMT6 and UPP1 were detected using TCGA database analysis, q PCR, and immunohistochemistry. Spearman rank correlation analysis was used to analyze the correlation between PRMT6, UPP1 protein expression and clinicopathological parameters. Kaplan-Meier survival analysis and Cox proportional hazard regression model were used to evaluate the effect of PRMT6 and UPP1 expression on postoperative progression-free survival. Results TCGA database analysis showed that the expression of PRMT6 and UPP1 mRNA in NMIBC cancer tissues was significantly higher than that in adjacent normal tissues(both P < 0.001). qPCR results showed that the relative expression levels of PRMT6 and UPP1 mRNA in NMIBC cancer tissues were(2.35 ± 0.49) and(2.87 ± 0.56), respectively, which were significantly higher than those in adjacent normal tissues(0.98 ± 0.26) and(1.02 ± 0.24)(t = 28.590, 35.150, both P <0.001). PRMT6 and UPP1 proteins were localized in the cytoplasm and cell membrane. The positive rates of PRMT6 and UPP1 in cancer tissues were 61.19%(82/134)and 64.18%(86/134), respectively, which were significantly higher than those in adjacent normal tissues(8.96% [12/134]and 7.46% [10/134])(χ2= 80.289, 93.748, both P <0.001). The positive rates of PRMT6 and UPP1 in tumor stage T1 and high-grade pathological grade were significantly higher than those in Ta/Tis stage and low grade(χ2= 16.181/<0.001, 14.074/<0.001, 7.370/0.007, 14.183/<0.001). The expression of PRMT6 and UPP1 in NMIBC cancer tissues was correlated with tumor diameter, tumor number, tumor stage, and pathological grade(rs/P = 0.512/<0.001, 0.604/<0.001, 0.578/<0.001, 0.553/<0.001;rs/P = 0.623/<0.001, 0.715/<0.001, 0.588/<0.001, 0.521/<0.001). During follow-up, there were 28 cases of recurrence, 16 cases of distant metastasis, and 6 cases of death. The 3-year progression-free survival rate was 62.69%(84/134). The 3-year progression-free survival rate of PRMT6-positive and UPP1-positive patients was 47.56%(39/82) and 50.00%(43/86), respectively, which were significantly lower than that of PRMT6-negative(87.50% [45/52]) and UPP1-negative patients(85.42%[41/48])(Log-rankχ2= 19.210, 16.580, both P <0.001). NMIBC T1 stage, high pathological grade, PRMT6 positivity, and UPP1 positivity were independent risk factors for poor prognosis of NMIBC [HR(95%CI) = 1.464(1.164-1.841), 1.385(1.070-1.794), 1.287(1.066-1.553), 1.267(1.079-1.488)]. Conclusion Both PRMT6 and UPP1 are highly expressed in NMIBC, which are associated with poor clinicopathological features and poor prognosis, and provide a theoretical basis for the formulation of clinical intervention strategies.