The Performance of GALAD Score for Diagnosing Hepatocellular Carcinoma in Patients with Chronic Liver Diseases: A Systematic Review and Meta-Analysis.

Background GALAD score, comprising five clinical parameters, is a predictive model developed for hepatocellular carcinoma (HCC) detection. Since its emergence, its diagnostic ability has been validated in different populations with a wide variation. Therefore, we conducted a meta-analysis to investigate its overall diagnostic performance in differentiating HCC in chronic liver diseases. Methods Eligible studies were searched in the Web of Science, PubMed, Scopus, Ovid, Cochrane Library, and Embase databases by 29 May 2022. Pooled sensitivity, pooled specificity, and area under the receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals (CI) were estimated. Results Fifteen original studies (comprising 19,021 patients) were included. For detecting any-stage HCC, GALAD score yielded an excellent ability, with pooled sensitivity, specificity, and AUC of 0.82 (95%CI: 0.78-0.85), 0.89 (95%CI: 0.85-0.91), and 0.92 (95%CI: 0.89-0.94), respectively. Notably, further analyses demonstrated a good diagnostic accuracy of GALAD score for identifying Barcelona Clinic Liver Cancer staging (BCLC) 0/A HCC, with a moderate sensitivity (0.73 (95%CI: 0.66-0.79)) and a high specificity (0.87 (95%CI: 0.81-0.91)); by contrast, only 38% of early-stage patients can be identified by alpha-fetoprotein, with an AUC value of 0.70 (95%CI: 0.66-0.74). Following subgroup analyses based on different HCC etiologies, higher sensitivities and AUC values were observed in subgroups with hepatitis C or non-viral liver diseases. For detecting BCLC 0/A HCC in the cirrhotic population, GALAD score had a pooled sensitivity, specificity, and AUC of 0.78 (95%CI: 0.66-0.87), 0.80 (95%CI: 0.72-0.87), and 0.86 (95%CI: 0.83-0.89). Conclusions We highlighted the superior diagnostic accuracy of GALAD score for detecting any-stage HCC with a high sensitivity and specificity, especially for early-stage HCC, with a relatively stable diagnostic performance. The addition of GALAD score into ultrasound surveillance may identify more HCC patients. Our findings imply the robust power of the GALAD score as a HCC screening or diagnostic tool, and it should be further validated by more studies with high quality.

Restless legs syndrome in maintenance hemodialysis patients: an epidemiologic survey in Hefei.

OBJECTIVE: To investigate the prevalence of restless legs syndrome (RLS) in maintenance hemodialysis (MHD) patients and its possible influencing factors. METHODS: MHD patients were consecutively enrolled from five hemodialysis centers in Hefei. Clinical, demographics, and laboratory data were recorded from December 2013 to March 2014. RLS diagnosis scale, Zung Self-Rating Depression Scale (SDS), Zung Self-Rating Anxiety Scale (SAS), Pittsburgh Sleep Quality Index (PSQI), and kidney disease and quality of life (KDQOLTM-36) were used for analysis. RESULTS: A total of 269 MHD patients (81 women, 188 men) were enrolled, among which 39 patients were diagnosed as RLS. The median duration of dialysis therapy was 33 months and the prevalence of RLS was 14.5%. Compared with RLS-negative patients, RLS-positive patients had lower hemoglobin level (98.67 ± 13.50 vs 106.34 ± 17.75, P = 0.011) and higher alkaline phosphatase concentration [131.0 (98.0, 226.0) vs 94.0 (69.8, 157.5), P = 0.001]. The multivariate logistic regression showed that high hemoglobin level (OR 0.975, 95% CI 0.956-0.995, P = 0.015) was a protective factor for RLS, while high alkaline phosphatase (OR 1.003, 95% CI 1.001-1.005, P = 0.018) was an independent risk factor for RLS. RLS patients had significantly higher PSQI scores (P < 0.001), reduced subjective sleep quality (P < 0.001), increased sleep latency (P < 0.007), shorter sleep duration (P < 0.001), lower sleep efficiency (P = 0.001), higher sleep disturbances (P < 0.001), and increased daytime dysfunction (P = 0.019). CONCLUSION: Our findings demonstrated that the prevalence of RLS was 14.5% in Hefei. High hemoglobin level was a protective factor for RLS, and high alkaline phosphatase was an independent risk factor. RLS affects many aspects of quality of life and sleep quality, which may contribute to the presence of depression and anxiety.

Regulation of mRNA expression of matrix extracellular phosphoglycoprotein (MEPE)/ osteoblast/osteocyte factor 45 (OF45) by fibroblast growth factor 2 in cultures of rat bone marrow-derived osteoblastic cells.

Matrix extracellular phosphoglycoprotein (MEPE)/ osteoblast/osteocyte factor 45 (OF45) is a recently isolated RGD-containing matrix protein that acts as the tumor-derived phosphaturic factor in oncogenic hypophosphatemic osteomalacia. It is also highly expressed by osteoblasts and osteocytes. We examined the regulation of MEPE/OF45 mRNA expression in osteoblastic cells derived from high-density cultures of primary rat bone marrow stromal cells incubated with dexamethasone, beta-glycerophosphate, and ascorbic acid. The level of MEPE/OF45 mRNA in these cells was down-regulated by the addition of fibroblast growth factor 2 (FGF2) for 48 h. These effects were observed in a dose-dependent manner between 2 and 10 ng/mL. FGF2 also reduced the expression of osteocalcin mRNA in these cells. In contrast, bone sialoprotein mRNA expression was increased by FGF2, while alpha1(I) procollagen mRNA expression was not altered. Additionally, neither Runx2 and osterix mRNA expression nor cell proliferation were affected by the addition of FGF2 in these high-density cultures, indicating that regulation by FGF2 may not be dependent on these transcription factors or on the proliferation of cells. Experiments using actinomycin D indicated that FGF2 decreased the stability of the MEPE/OF45 mRNA. Moreover, inhibition of a specific mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase (MEK) by PD98059 blocked FGF2-regulated MEPE/OF45 expressions, indicating that this regulation requires the MAPK pathway. These results suggest that MEPE/OF45 gene is one of the targets of FGF2 and may play an important role during bone formation and calcification.

Periodontal ligament cells under intermittent tensile stress regulate mRNA expression of osteoprotegerin and tissue inhibitor of matrix metalloprotease-1 and -2.

We studied the mRNA expression of osteoprotegerin (OPG), receptor activator of NF-kappa B ligand (RANKL), tissue inhibitor of matrix metalloprotease (TIMP)-1 and -2, and matrix metalloprotease (MMP)-1 and -2 by human periodontal ligament (PDL) cells under intermittent tensile stress using a Flexercell Strain Unit. Analysis by reverse transcriptase-polymerase chain reaction showed that mechanical force upregulated OPG mRNA. We also demonstrated that the protein concentration of OPG in conditioned medium increased upon loading with tensile stress, as determined by enzyme-linked immunosorbent assay. TIMP-1 and -2 mRNA levels also increased, whereas levels of RANKL, MMP-1, and MMP-2 mRNA were barely affected. We further examined the effect of loading with tensile stress and addition of Salmonella abortus equi lipopolysaccharide (LPS) on the mRNA expression of PDL cells. The amount of OPG mRNA induced by mechanical strain was found to decrease with the addition of LPS to cultures. The induction of OPG mRNA expression by stretching was inhibited in the presence of indomethacin or genistein, whereas TIMP-1 mRNA expression induced by stretching was inhibited by the addition of cycloheximide, suggesting that tensile stress regulates cyclooxygenase activities, tyrosine phosphorylation, and de novo protein synthesis in PDL cells through the induction of OPG and TIMP-1 mRNA expression. These results provide evidence that the mechanical stimulus of stretching is responsible for the observed regulation of bone resorption and tissue degradation in PDL tissue.

Type I collagen regulated dentin matrix protein-1 (Dmp-1) and osteocalcin (OCN) gene expression of rat dental pulp cells.

In this study, we investigated the effect of type I collagen on dentin matrix protein-1 (Dmp-1) and osteocalcin (OCN) gene expression of dental pulp cells. The mRNA level of Dmp-1 gene was down-regulated; however, OCN gene expression was up-regulated by the culture of dental pulp cells with type I collagen. These findings imply that type I collagen regulates mRNA level of Dmp-1 and OCN gene that are predominantly expressed in active odontoblasts. The change of gene expression by type I collagen was suppressed by the blocking of collagen-integrin interaction. We could conclude that the effect of type I collagen was mediated via binding of collagen to integrin receptors.