Association between serum antinuclear antibody and rheumatoid arthritis.

Background: The relationship between serum antinuclear antibody (ANA) and rheumatoid arthritis (RA) remains unknown. Therefore, we aimed to evaluate whether serum ANA was associated with an increased risk of RA in a case-control study. Methods: Patients with rheumatoid arthritis hospitalized at Shandong Provincial Hospital from January 2018 to December 2022 were recruited as the case group, and patients with other types of arthritis and healthy people at the same time were taken as the control group. Antinuclear antibody (ANA) was detected by indirect immunofluorescence assays. Propensity score matching was employed to construct a cohort of patients exhibiting comparable baseline characteristics. The relationship between serum ANA and the risk of rheumatoid arthritis was analyzed by logistic regression analysis. Results: A total of 1,175 patients with RA and 1,662 control subjects were included in this study. After adjusting for potential confounding factors in the propensity-score matched cohort, the risk of RA gradually increased with rising of ANA titers. When ANA titers were divided into three groups (1:100, 1:320, and 1:1,000), the OR (95% CI) for ANA titers from low to high was 3.95 (3.01, 5.18), 16.63 (9.44, 29.30), and 17.34 (9.53, 31.54), respectively, compared to those when ANA was negative. The ANA patterns closely related to the occurrence of RA include nuclear homogeneous, nuclear speckled, and cytoplasmic speckled. Among them, the positive rate of nuclear homogeneous was the highest, which accounted for 42.64%. The OR (95% CI) of ANA patterns including nuclear homogeneous, nuclear speckled, and cytoplasmic speckled was 16.81 (11.46, 24.65), 3.40 (2.49, 4.63), and 3.09 (1.77, 5.40), respectively. Conclusion: There was a curve relation between ANA titer and RA, and the higher the ANA titer, the higher the probability of RA. However, there was no statistical difference in probability of RA for 1:320 versus 1:1,000 ANA titers. The most important kind of ANA pattern in the blood of RA patients was nuclear homogeneous. These findings suggest that ANA may be a novel risk marker for RA.

PBX3 as a biomarker for the early diagnosis and prediction of prognosis of glioma.

BACKGROUND: Increasing evidence have elucidated that PBX3 played a crucial role in cancer initiation and progression. PBX3 was differentially expressed in many cancer types. However, PBX3 potential involvement in gliomas remains to be explored. METHODS: The expression level of PBX3 in glioma tissues and glioma cells, and its correlation with clinical features were analyzed by data from TCGA, GEPIA, CGGA and CCLE. Univariable survival and Multivariate Cox analysis was used to compare several clinical characteristics with survival. We also analyzed the correlation between PBX3 expression level and survival outcome and survival time of LGG and GBM patients by using linear regression equation. GSEA was used to generate an ordered list of all genes related to PBX3 expression and screening of genes co-expressed with PBX3 mRNA by "limma" package. RESULTS: The results showed that PBX3 was highly expressed in gliomas and its expression increased with the increase of malignancy. Survival analysis found that PBX3 is more valuable in predicting the OS and PFI of LGG patients than that of GBM. For further study, TCGA and CGGA data were downloaded for univariate Cox analysis and multivariate Cox analysis which showed that the expression of PBX3 was independent influencing factors for poor prognosis of LGG patients. Meanwhile, Receiver operating characteristic (ROC) curve showed that PBX3 was a predictor of overall survival rate and progression-free survival rate of LGG. Linear regression model analysis indicated that the higher expression of PBX3 the higher the risk of death of LGG patients, and the higher expression of PBX3 the higher the risk of disease progression of LGG patients. Next, TCGA data were downloaded for GSEA and Co-expression analyses, which was performed to study the function of PBX3. CONCLUSION: PBX3 may be involved in the occurrence and development of glioma, and has potential reference value for the early diagnosis and prediction of prognosis of glioma.

An Efficient Nomogram for Discriminating Intrahepatic Cholangiocarcinoma From Hepatocellular Carcinoma: A Retrospective Study.

Objective: This study aims to establish a nomogram and provide an effective method to distinguish between intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). Methods: A total of 1,591 patients with HCC or ICC hospitalized at Shandong Provincial Hospital between January 2016 and August 2021 were included and randomly divided into development and validation groups in a ratio of 3:1. Univariate and multivariate analyses were performed to determine the independent differential factors between HCC and ICC patients in the development cohort. By combining these independent differential factors, the nomogram was established for discriminating ICC from HCC. The accuracy of the nomogram was estimated by using receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Furthermore, the predictive nomogram was assessed in the internal testing set. Results: Through multivariate analysis, independent differential factors between HCC and ICC involved hepatitis B virus (HBV), logarithm of alpha-fetoprotein (Log AFP), logarithm of protein induced by vitamin K absence or antagonist-II (Log PIVKA-II), logarithm of carbohydrate antigen 199 (Log CA199), and logarithm of carbohydrate antigen 125 (Log CA125). A nomogram was finally established by incorporating these five independent differential factors. Comparing a model of conventional tumor biomarkers including AFP and CA199, the nomogram showed a better distinction between ICC and HCC. The area under the ROC curve (AUC) of ICC diagnosis was 0.951 (95% CI, 0.938-0.964) for the nomogram. The results were consistent in the validation cohort with an AUC of 0.958 (95% CI, 0.938-0.978). After integrating patient preferences into the analysis, the DCA showed that using this nomogram to distinguish ICC and HCC increased more benefit compared with the conventional model. Conclusion: An efficient nomogram has been established for the differential diagnosis between ICC and HCC, which may facilitate the detection and diagnosis of ICC. Further use of the nomogram in multicenter investigations will confirm the practicality of the tool for future clinical application.

Value of AFP and PIVKA-II in diagnosis of HBV-related hepatocellular carcinoma and prediction of vascular invasion and tumor differentiation.

BACKGROUND: To explore the value of alpha fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in diagnosis of HBV-related hepatocellular carcinoma (HCC) and their relationship with vascular invasion, tumor differentiation and size. METHODS: A total of 433 participants were enrolled in this study including 266 cases with HBV-related HCC, 87 cases with HBV DNA positive benign liver disease and 80 healthy individuals. Then we explored the correlation between AFP, PIVKA-II serum level and several pathological features such as vascular invasion, tumor differentiation and size. The value of these two markers used singly or jointly in diagnosing HBV-related HCC was evaluated by receiver operating characteristic (ROC) curve. The ROC curve was also plotted to identify AFP, PIVKA-II serum cut-off values that would best distinguish HBV-related HCC patients with and without vascular invasion. RESULTS: The level of AFP and PIVKA-II in HBV-related HCC group was significantly higher (Z was 7.428, 11.243 respectively, all P < 0.01). When AFP and PIVKA-II were used as the individual tumor marker, the areas under the ROC curve (AUC) of HBV-related HCC diagnosis were 0.765 (95% CI, 0.713 ~ 0.8170) for AFP, 0.901 (95% CI, 0.868 ~ 0.935) for PIVKA-II, and 0.917 (95% CI, 0.886 ~ 0.948) for AFP and PIVKA-II simultaneously. The serum levels of AFP and PIVKA-II were positively correlated with tumor differentiation and size. High AFP and PIVKA-II expression was significantly associated with the presence of vascular invasion (P was 0.007 and 0.014 respectively). The AFP level > 64.4 ng/ml or PIVKA-II level > 957.61mAU/ml was the best critical value to predict the presence of vascular invasion. CONCLUSION: Our results validate that AFP and PIVKA-II play a significant role in the diagnosis of HBV-related HCC. The diagnostic value of AFP and PIVKA-II combined detection or single assay of PIVKA-II is higher than that of separate assay of AFP. Moreover, their concentration has important clinical value in judging tumor size, tumor cell differentiation and vascular invasion.

MiR-320 inhibits the growth of glioma cells through downregulating PBX3.

BACKGROUND: MiR-320 is downregulated in multiple cancers, including glioma and acts as tumor suppressor through inhibiting tumor cells proliferation and inducing apoptosis. PBX3 (Pre-B cell leukemia homeobox 3), a putative target gene of miR-320, has been reported to be upregulated in various tumors and promote tumor cell growth through regulating MAKP/ERK pathway. This study aimed to verify whether miR-320 influences glioma cells growth through regulating PBX3. METHODS: Twenty-four human glioma and paired adjacent nontumorous tissues were collected for determination of miR-320 and PBX3 expression using RT-qPCR and western blot assays. Luciferase reporter assay was performed to verify the interaction between miR-320 and its targeting sequence in the 3' UTR of PBX3 in glioma cells U87 and U251. Increased miR-320 level in U87 and U251 cells was achieved through miR-320 mimic transfection and the effect of which on glioma cells growth, proliferation, cell cycle, apoptosis and activation of Raf-1/MAPK pathway was determined using MTT, colony formation, flow cytometry and western blot assays. PBX3 knockdown was performed using shPBX3 and the influence on MAPK pathway activation was evaluated. RESULTS: MiR-320 downregulation and PBX3 upregulation was found in glioma tissues. Luciferase reporter assays identified miR-320 directly blinds to the 3' UTR of PBX3 in glioma cells. MiR-320 mimic transfection suppressed glioma cells proliferation, and induced cell cycle arrest and apoptosis. Both miR-320 overexpression and PBX3 knockdown inhibited Raf-1/MAPK activation. CONCLUSION: MiR-320 may suppress glioma cells growth and induced apoptosis through the PBX3/Raf-1/MAPK axis, and miR-320 oligonucleotides may be a potential cancer therapeutic for glioma.

MiR-320 inhibits the growth of glioma cells through downregulating PBX3

BACKGROUND: MiR-320 is downregulated in multiple cancers, including glioma and acts as tumor suppressor through inhibiting tumor cells proliferation and inducing apoptosis. PBX3 (Pre-B cell leukemia homeobox 3), a putative target gene of miR-320, has been reported to be upregulated in various tumors and promote tumor cell growth through regulating MAKP/ERK pathway. This study aimed to verify whether miR-320 influences glioma cells growth through regulating PBX3. METHODS: Twenty-four human glioma and paired adjacent nontumorous tissues were collected for determination of miR-320 and PBX3 expression using RT-qPCR and western blot assays. Luciferase reporter assay was performed to verify the interaction between miR-320 and its targeting sequence in the 3' UTR of PBX3 in glioma cells U87 and U251. Increased miR-320 level in U87 and U251 cells was achieved through miR-320 mimic transfection and the effect of which on glioma cells growth, proliferation, cell cycle, apoptosis and activation of Raf-1/MAPK pathway was determined using MTT, colony formation, flow cytometry and western blot assays. PBX3 knockdown was performed using shPBX3 and the influence on MAPK pathway activation was evaluated. RESULTS: MiR-320 downregulation and PBX3 upregulation was found in glioma tissues. Luciferase reporter assays identified miR-320 directly blinds to the 3' UTR of PBX3 in glioma cells. MiR-320 mimic transfection suppressed glioma cells proliferation, and induced cell cycle arrest and apoptosis. Both miR-320 overexpression and PBX3 knockdown inhibited Raf-1/MAPK activation. CONCLUSION: MiR-320 may suppress glioma cells growth and induced apoptosis through the PBX3/Raf-1/MAPK axis, and miR-320 oligonucleotides may be a potential cancer therapeutic for glioma.

Tunable fluorescent pH sensor based on water-soluble perylene tetracarboxylic acid/Fe(3+).

A novel fluorescent pH sensor with tunable response range was designed based on highly fluorescent 3,4:9,10-perylene tetracarboxylic ammonium, which could coordinate the paramagnetic Fe(3+) ions to turn off its fluorescence and could also release Fe(3+) to turn on the fluorescence again at higher pH. The fluorescent pH sensor was tunable in the presence of different ligands in aqueous solution.

Zinc(II)-selective ratiometric fluorescent probe based on perylene bisimide derivative.

A fluorescent probe of N,N'-biscyclohexyl-1,7-di(3-pyridoxy)-perylene-3,4:9,10-tetracarboxylic acid diimide has been synthesized, and exhibited excellent selectivity and sensitivity for Zn(2+) over other competing biological cations. The Zn(2+) -selective fluorescence blue-shift and enhancing property in conjunction with a visible colorimetric change from orange to green could be observed. With favorable photophysical properties in the visible region, the perylene bisimide derivatives remarkably improved the performance of the probe.

Expression and clinical significance of hepaCAM and VEGF in urothelial carcinoma.

PURPOSE: Investigate the expression of hepatocyte cell adhesion molecule (hepaCAM) and vascular endothelial growth factor (VEGF) mRNA in 55 cases of urothelial carcinoma to examine the potential relationship between hepaCAM and VEGF in urothelial carcinoma. METHODS: Expression of hepaCAM and VEGF gene was determined by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) in 55 paired urothelial carcinoma specimens. T24 cells stably expressing hepaCAM gene were established by Lipofectamine 2000. RT-PCR and western blot analysis were used to detect gene and protein expression of hepaCAM and VEGF before and after transfection. MTT test was used to detect the effect of hepaCAM gene on the cell proliferation. RESULTS: RT-PCR showed that hepaCAM expression level was significantly lower, and VEGF was significantly higher in urothelial carcinoma tissues than in adjacent tissues (P < 0.05, P < 0.05). hepaCAM and VEGF were strongly correlated with tumor stage (P < 0.05, P < 0.05). Spearman correlation analysis showed lower hepaCAM level was associated with higher VEGF level (r = -0.277 P = 0.041). Experiments with T24 cells in vitro demonstrated the expression of VEGF mRNA and protein were significantly decreased after transfection of hepaCAM gene (P < 0.05, P < 0.05). Expression of hepaCAM resulted in a significant inhibition of T24 cells proliferation (P < 0.05). CONCLUSION: There is a close relationship between hepaCAM and VEGF in urothelial carcinoma. hepaCAM may be defined as a new target for diagnosis and anticancer therapy.

Exon 2 methylation inhibits hepaCAM expression in transitional cell carcinoma of the bladder.

AIM: We aimed to investigate the mechanisms of hepaCAM inactivation in transitional cell carcinoma of the bladder through the analysis of hepaCAM exon 2 methylation. METHODS: The methylation of hepaCAM exon 2 and the expression of hepaCAM were determined by methylation-specific restriction PCR assay and RT-PCR in bladder cancer cells (T24, BIU-87) as well as in 55 paired bladder cancer specimens. The methylated bladder cancer cells were treated with 5-Aza- 2'-deoxycytidine (5-Aza-CdR), a demethylating agent. MTT was used to detect the proliferation of T24 and BIU-87 cells. RESULTS: The proliferation of T24 and BIU-87 cells was suppressed by treatment with different concentrations of 5-Aza-CdR; the expression of hepaCAM was absent in T24 and BIU-87 cells, and we found that exon 2 of hepaCAM was methylated in the 2 cells. hepaCAM mRNA was re-expressed and the methylation status of hepaCAM exon 2 was reversed after treatment with 5-Aza-CdR. The expression of hepaCAM mRNA in bladder cancer tissues was significantly lower than that in adjacent tissues. The methylation rate of hepaCAM exon 2 was significantly higher in bladder cancer tissues than in adjacent tissues. The methylation of hepaCAM exon 2 was related to hepaCAM expression in bladder cancer tissues. CONCLUSIONS: Downregulation of hepaCAM expression plays an important role in the tumorigenesis and development of bladder cancer. DNA methylation may be important for downregulation of hepaCAM expression in bladder cancer.