Zinc finger protein 382 (ZNF382), a member of the Kriippel-associated box zinc finger proteins (KRAB-ZFPs) family, plays critical roles in regulating certain downstream genes expression as a transcription inhibitor. ZNF382 is downregulated in multiple tumors due to hypermethylation of its promoter, to be more specific, methylation of promoter CpG island may contributes to inhibition of gene expression as found in many studies. With application of DNA methyltransferase inhibitors (DNMTi) 5-azacytidine and 5-aza-2'-deoxycytidine, hypomethylation of ZNF382 gene may contribute to anti-tumor effects. This review summerized the structure, biological functions, expression and the roles of ZNF382 in multiple cancers, and, expression of ZNF382 regulated by promoter methylation was further discussed to show the possibilities of DNA hypomethylation treatment as a potential treatment in clinical applications.
Background: Osteopontin (OPN), a matricellular protein, is greatly generated from brain tissues after acute brain injury. We determine the relationship between plasma OPN concentrations and outcome after acute intracerebral hemorrhage (ICH) in a clinical setting. Methods: In this prospective, observational study enrolling 162 ICH patients and 162 healthy controls, hemorrhagic severity was assessed using National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volumes, a poor outcome was defined as modified Rankin Scale > 2 at poststroke 90 days, and early neurologic deterioration (END) was defined as an increase of >= 4 points in the NIHSS score or death at 24 h from symptoms onset. Results: Plasma OPN concentrations were significantly higher in patients than in controls (median value, 1287.6 vs. 405.7 pmol/l; P < 0.001). OPN concentrations were strongly correlated with admission NIHSS scores (r value = 0.520) and hematoma volumes (r value = 0.468). Areas under receiver operating characteristic curve for poor outcome and END were 0.811 and 0.753 respectively. Plasma OPN emerged as an independent predictor of functional outcome and END, with odds ratio values of 3.897 and 6.004 respectively. Conclusions: Plasma OPN could serve as a useful prognostic biomarker in ICH.
Background The albumin to fibrinogen ratio (AFR) and the C-reactive protein to albumin ratio (CAR) have been served as inflammatory markers. However, their roles in RA remain unclear. We investigated the association of AFR/CAR with the concentration of autoantibodies and Th17 cells in RA. Methods: A total of 196 RA patients, 200 patients with systemic lupus erythematosus (SLE), and 200 healthy donors (HD) who were admitted to the First Affiliated Hospital of Fujian Medical University were enrolled. The results of FIB, ALB, CRP, anti-cyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF) and erythrocyte sedimentation rate (ESR) from RA patients and SLE patients were retrospectively analyzed. The percentage of Th17 cells in peripheral blood of RA patients was detected by flow cytometry, and the relative expression of TNF-alpha, IL-6 and IL-17A was detected by RT-qPCR. Correlation analysis of AFR/CAR and Th17 cells, CRP, ESR, TNF-alpha, IL-6 and IL-17A in RA was conducted. Results: Compared with SLE patients and healthy donors (HD), AFR concentration was significantly lower (P < 0.01) in RA patients, while CAR concentration was significantly increased (P < 0.01) in RA patients. AFR showed negative correlation with CRP (r = - 0.7103), ESR (r = -0.6542), RF ( -0.2219), Th17 cells (r = - 0.5952) and IL-17A (r = - 0.4681). CAR was positively correlated with CRP (r = 0.9899), ESR (r = 0.605), RF (0.1867), Th17 cells (r = 0.6818), TNF-alpha (r = 0.3388), and IL-17A (r = 0.2046). Conclusions: The concentration of AFR in RA patients was reduced, while CAR concentration was increased. AFR and CAR are associated with CRP, ESR, RF, and Th17 cell ratios in RA patients, which can be used as potential indicators for determining RA inflammation.
Background: The prevalence of cytomegalovirus in China is high and the infection could result in disastrous consequences. Cellular immunity is the main mechanism for virus controlling. We explored the performance of cytomegalovirus antigen-specific enzyme-linked immunospot assay in patients with different infection states in endemic area. Methods: Twenty-eight patients with reliable results were included in statistical analysis. Peripheral blood mononuclear cells were extracted and were stimulated by cytomegalovirus phosphoprotein 65 or immediate early protein-1 antigen respectively. Spot forming cells (SFCs) were counted to evaluate the cellular immune response elicited by antigens. Results: Spots could be clearly displayed, and evenly dispersed with a clean background. The numbers of SFCs were 0 [0-0], 426 [210-601] and 230 [57-513] for uninfected individuals (n = 7), latently infected patients (n = 11) and actively infected patients (n = 10) respectively, which were statistically different. The number of SFCs stimulated by phosphoprotein 65 was significantly higher than that by immediate early protein-1. Conclusions: The number of SFCs was significantly different among patients with different infection state. The stimulatory effect of phosphoprotein 65 was better than that of immediate early protein-1.
Several markers and prognostic scores have been identified for predicting the development and progression of liver disease; among them, haematological parameters (the neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), red cell distribution width (RDW), RDW to platelet ratio (RPR), mean platelet volume (MPV), and mean corpuscular volume (MCV)) have recently gained significant interest. Compared with traditional prognostic factors, haematological indices are easy to obtain and relatively inexpensive. There is growing evidence that these haematological indices play a key role in HBV-related liver diseases and has been proposed as a predictive marker of adverse outcomes in these patients. This article focuses on discussing the diagnostic and prognostic value of the haematological indices in patients with HBV-related liver diseases.
Myhre syndrome is a rare autosomal dominant multi-organ disorder characterized by growth retardation, skeletal anomalies, muscular hypertrophy, joint stiffness, facial dysmorphism, deafness, cardiovascular disease, and abnormal sexual development. Here we described the first two Chinese Myhre syndrome patients diagnosed by whole-exome sequencing. They both had de novo c.1498A > G (p.Ile500Val) variant in SMAD4 and presented with key characteristics of Myhre syndrome but also revealed uncommon features (polydactyly in the girl and precocious puberty in the boy). We performed functional analysis on four previously reported SMAD4 pathogenic variants in Myhre syndrome patients using dual-luciferase assay. Our results revealed that the pathogenic variants resulted in a variable degree of increased transcription activity of target genes that contain the minimal SMAD binding elements in their promoter regions. The boy responded to the recombinant human growth hormone treatment with improved height but also led to hyperinsulinemia and advanced bone age. Because of his precocious puberty, we subsequently combined the recombinant human growth hormone and gonadotrophin-releasing hormone agonist treatments, which resulted in overall improved height. We reviewed the sexual features of reported Myhre syndrome cases and discussed the possible mechanism of SMAD4 variants in Myhre syndrome that lead to the abnormal hypothalamic-pituitary-gonadal axis.
Background: We evaluated the application value of Xpert MTB/RIF and T-SPOT.TB in the diagnosis of bone and joint tuberculosis. Methods: One hundred two patients with suspected bone and joint tuberculosis (BJTB) were admitted to Zhengzhou Orthopaedics Hospital, Henan, China from April 2018 to February 2019. The Xpert MTB/RIF and T-SPOT.TB tests were performed using pus specimens and peripheral blood, respectively. The diagnostic performance of Xpert MTB/RIF and T-SPOT.TB tests was evaluated on the basis of the composite reference standard (CRS). Result A Total of 73 suspected BJTB were enrolled and categorized, including 12 confirmed BJTB, 27 probable BJTB and 34 non-BJTB. When CRS was used as the reference, the specificity, PPV and NLR values of the Xpert MTB/RIF assay were significantly higher than those of the T-SPOT.TB assay (97.1% vs. 82.4%, p < 0.05; 96.7% vs. 85.4%, p < 0.05; 0.26 vs. 0.12, p < 0.05). However, the sensitivity, NPV and PLR values of the T-SPOT. TB assay were significantly higher than those of the Xpert MTB/RIF assay (89.7% vs. 74.4%, p < 0.05; 87.5% vs. 76.7%, p < 0.05; 5.08 vs. 2.52,p < 0.05). The AUCs from Xpert MTB/RIF and T-SPOT. TB tests were 0.857 and 0.860, respectively. However, the difference was not statistically significant. The Xpert MTB/RIF and T-SPOT. TB tests demonstrated medium concordance in diagnosing BJTB. Conclusion: The sensitivity of T-SPOT.TB test combined with the specificity of Xpert MTB/RIF not only shorten the time of diagnosis but also improve the accuracy of diagnosis of BJTB and reduce the misdiagnosis rate. Therefore, they are useful for early diagnosis of BJTB.
Long noncoding RNAs (lncRNAs) play an important role in tumor development. With the development of sequencing technology, many new lncRNAs have been discovered. lncRNA TP73-AS1 is abnormally expressed in many cancers. A summary of the current literature related to TP73-AS1 reveals that TP73-AS1 mainly regulates the occurrence and development of tumors through the mechanism of competitive endogenous RNA (ceRNA). In addition, the abnormal expression of TP73-AS1 can regulate the malignant function of tumor cells through a variety of possible mechanisms. All evidence suggests that TP73-AS1 may be a potential diagnostic biomarker or a new cancer therapeutic target.
The SREBP2/LDLR pathway is sensitive to cholesterol content in the endoplasmic reticulum (ER), while membrane low-density lipoprotein receptor (LDLR) is influenced by sterol response element binding protein 2 (SREBP2), pro-protein convertase subtilisin/kexin type 9 (PCSK9) and inducible degrader of LDLR (IDOL). LDL-C, one of the risk factors in cardiovascular disease, is cleared through endocytosis recycling of LDLR. Therefore, we propose that a balance between LDLR endocytosis recycling and PCSK9-mediated and IDOL-mediated lysosomal LDLR degradation is responsible for cholesterol homeostasis in the ER. For statins that decrease serum LDL-C levels via cholesterol synthesis inhibition, the mechanism by which the statins increase the membrane LDLR may be regulated by cholesterol homeostasis in the ER.
Background: Evidence about whether remnant cholesterol (RC), especially non-fasting RC, is a causal risk factor for coronary heart disease (CHD) in Chinese subjects is rare. Recently, estimated RC level (RCe) was applied in many studies with large population. We aimed to compare fasting and non-fasting RCe calculated by LDL-C level determined by different methods in Chinese subjects, and investigate their contributions to CHD. Methods: Levels of TC, TG and HDL-C were measured directly in 273 CHD patients (CHD group) and 136 controls (CON group) before and at 4 h after a daily breakfast. LDL-C level was measured directly or calculated by Friedewald equation at TG < 4.5 mmol/L. RC level estimated by calculated or measured LDL-C was termed as RCe1 or RCe2. Contributions of different RC levels to CHD were evaluated by multivariable logistic regression analysis. Results: Both RCe1 and RCe2 increased significantly at 4h after breakfast (both p < 0.05). RCe1 was significantly higher than RCe2 in fasting or non-fasting state (p < 0.05). RCe1 was closely related to RCe2, especially in the highest quartile of RCe1 (p < 0.05). Non-fasting RCe1 or RCe2 and fasting RCe2 independently predicted CHD after adjustment for traditional risk factors (all p < 0.05). Conclusions: Although RCe1 was significantly higher than RCe2, non-fasting RCe, no matter RCe1 or RCe2, after a daily breakfast was an independent predictor for CHD risk in Chinese subjects, indicating that the non-fasting state is critical in the development of atherosclerosis.
Background: Type 2 diabetes (T2D), a typical metabolic disease, is closely associated with serum free fatty acids. But the association between serum total fatty acids (TFAs, free fatty acids plus esterified fatty acids) and T2D has not been reported. Methods: Serum esterified fatty acids were hydrolyzed under alkaline conditions, and serum TFAs were extracted after acidizing. Fourteen of serum TFAs in 1,828 serum samples, including 543 controls, 655 prediabetes, and 630 T2D patients, were simultaneously quantified based on the calibration curves of 8 fatty acids using matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS). Results: Correlation analysis revealed strong correlations among serum TFAs and ratios of the TFAs in T2D patients compared with controls or prediabetes both in males and females. Receiver operating characteristic analysis indicated that a panel including fasting plasma glucose, glycosylated hemoglobin type A1c, gammaglutamyltransferase, triglyceride, C18:1, and C20:3, has a good capability to distinguish prediabetes from T2D, with the sensitivity of 87.0%, the specificity of 91.0%, and the area under curve (AUC) of 0.96. Conclusions: In this study, rapid, absolute, and simultaneous quantification of serum TFAs was performed using MALDI-FTICR MS. C18:1 and C20:3 were significantly correlated with prediabetes and T2D.
Background: Oxidized low-density lipoprotein (ox-LDL) and its receptor, lectin-like ox-LDL receptor-1 (LOX-1) are involved in the pathogenesis of atherosclerosis. Expression of LOX-1 was substantially raised in the basilar arterial wall of subarachnoid hemorrhage (SAH) rabbits. We ascertained the relationship between serum soluble LOX-1 concentrations and functional outcome after human aneurysmal SAH. Methods: We enrolled 94 aneurysmal SAH patients and 94 healthy controls. Serum soluble TOX-1 concentrations were quantified using commercial enzyme-linked immunosorbent assay kit. A poor outcome was defined as Glasgow outcome scale score of 1-3. Results: Median values of serum soluble LOX-1 in stroke patients were significantly higher than those in controls (1.5 vs. 0.4 ng/ml, P < 0.001). Thirty patients (31.9%) had a poor outcome at 6 months after stroke. Serum soluble LOX-1 was a strong predictor of poor outcome (OR 5.20, 95% CI 1.25-22.04). Serum soluble LOX-1 concentrations exhibited a significant discriminatory capability (area under curve 0.811, 95% confidence interval 0.717-0.884). The predictive powers of World Federation of Neurological Surgeons grade, Hunt-Hess grade, modified Fisher grade, and serum soluble LOX-1 concentrations were comparable (all P > 0.05). Conclusions: Serum soluble LOX-1 appears to have the potential to become a promising prognostic predictor after human aneurysmal SAH.
Objective: Human epididymis protein 4 (HE4) has been suggested as a new biomarker for the detection of ovarian cancer. Because there are few reports on HE4 in terms of ovarian cancer diagnosis in the Chinese population, we evaluated the diagnostic performances of HE4 and the ROMA in Chinese women with pelvic masses. Methods: The serum concentrations of CA 125 and HE4 in 318 Chinese women with pelvic masses (39 of which were ovarian cancers) were determined. Results: For the discrimination of benign gynecological diseases from ovarian cancer, the sensitivity and specificity values were 87.2% and 75.8% for the ROMA and 51.3% and 97.3% for HE4. The ROMA also showed higher sensitivity than HE4 in both the early and advanced stages. In the ROC curve analysis, the AUC values for ROMA, HE4 and CA 125 were 0.927, 0.907 and 0.785, respectively. Conclusions: As a new tumor marker, HE4 shows high specificity and efficacy in the Chinese population, while the ROMA that combines HE4 and CA 125 shows high sensitivity and a high Youden's index. These markers should be extended to China since they have good diagnostic performances.
Background: Several international staging or scoring systems don't accurately predict overall survival (OS) after resection of primary hepatocellular carcinoma (PHCC). Therefore, we attempted to overcome this limitation by constructing the A-index and its associated nomogram. Methods: We selected 672 patients who underwent curative resection of PHCC between January 2007 and February 2015 at the first affiliated hospital of the Wenzhou medical university. These subjects were randomly divided into the training (n = 470) and the validation group (n = 202) according to the ratio of 7:3. Results: We prepared the nomogram using eight independent risk factors including the A-index (calculated by 100 x aspartate transaminase /albumin /albumin) in the training cohort. The concordance index (C-index) of the nomogram for both training and validation set was similar in indicating the OS rate. The nomogram showed the strongest predictive power for the 1-year, 3-year, and 5-year OS, with the area under the ROC curve being 0.8182, 0.7892, and 0.7669, respectively. Correction curves showed consistent performance for both groups, stratification of the Kaplan-Meier curve was significant (P < 0.001), and decision curve analysis (DCA) showed the superiority of nomograms considering clinical effects. Conclusions: The predictive power of the nomogram integrating the A-index for OS was optimal.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. HCC patients are commonly diagnosed at an advanced stage, for which highly effective therapies are limited. Hence, there is a growing need to discover promising biomarkers for HCC diagnosis, and in this context, microRNAs (miRNAs) hold great promise. MiRNAs function as gene expression regulators by directly binding messenger RNAs (mRNAs) and subsequently causing suppression of mRNA translation or degradation of target mRNAs. Two major types of noncoding RNAs act as competing endogenous sponges: circular RNAs and long non-coding RNAs. They can competitively bind to miRNA through miRNA response elements (MREs), thereby reducing the number of miRNAs binding mRNAs and regulating the expression of downstream target genes of miRNAs at the posttranscriptional level. The relationship between single miRNA sponge and HCC has been explored. However, comprehensive reviews on the sponge's function in HCC are lacking. In this review, we describe the methods to find endogenous sponges and construct exogenous sponges, and briefly compare endogenous and exogenous sponges. We also summarize the current progress on the functional role of miRNA sponges in HCC pathogenesis and present their potential value as diagnostic biomarkers and therapeutic targets. In-depth investigations on the function and mechanism of miRNA sponges in HCC will enrich our knowledge of HCC pathogenesis and contribute to the development of effective diagnostic biomarkers and therapeutic targets for HCC.