APC mutations disrupt ß-catenin destruction complex condensates organized by Axin phase separation.

The Wnt/ß-catenin pathway is critical to maintaining cell fate decisions. Recent study showed that liquid-liquid-phase separation (LLPS) of Axin organized the ß-catenin destruction complex condensates in a normal cellular state. Mutations inactivating the APC gene are found in approximately 80% of all human colorectal cancer (CRC). However, the molecular mechanism of the formation of ß-catenin destruction complex condensates organized by Axin phase separation and how APC mutations impact the condensates are still unclear. Here, we report that the ß-catenin destruction complex, which is constructed by Axin, was assembled condensates via a phase separation process in CRC cells. The key role of wild-type APC is to stabilize destruction complex condensates. Surprisingly, truncated APC did not affect the formation of condensates, and GSK 3ß and CK1α were unsuccessfully recruited, preventing ß-catenin phosphorylation and resulting in accumulation in the cytoplasm of CRCs. Besides, we propose that the phase separation ability of Axin participates in the nucleus translocation of ß-catenin and be incorporated and concentrated into transcriptional condensates, affecting the transcriptional activity of Wnt signaling pathway.

IGF2BP3 promotes the progression of colorectal cancer and mediates cetuximab resistance by stabilizing EGFR mRNA in an m6A-dependent manner.

Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an RNA-binding protein, is associated with tumorigenesis and progression. However, the exact molecular mechanisms of IGF2BP3 in colorectal cancer (CRC) oncogenesis, progression, and drug resistance remain unclear. This study found that IGF2BP3 was upregulated in CRC tissues. Clinically, the elevated IGF2BP3 level is predictive of a poor prognosis. Functionally, IGF2BP3 enhances CRC tumorigenesis and progression both in vitro and in vivo. Mechanistically, IGF2BP3 promotes epidermal growth factor receptor (EGFR) mRNA stability and translation and further activates the EGFR pathway by serving as a reader in an N6-methyladenosine (m6A)-dependent manner by cooperating with METTL14. Furthermore, IGF2BP3 increases the drug resistance of CRC cells to the EGFR-targeted antibody cetuximab. Taken together, our results demonstrated that IGF2BP3 was a functional and clinical oncogene of CRC. Targeting IGF2BP3 and m6A modification may therefore offer rational therapeutic targets for patients with CRC.

The Predictive Value of CA-125 and Hb for Ocular Metastasis in Hepatocellular Carcinoma Patients.

Objective: To explore the risk factors of ocular metastasis (OM) in patients with hepatocellular carcinoma (HCC) by analyzing the demographic characteristics and serum markers. Methods: From July 2002 to December 2012, 1064 HCC patients were included in our study. The chi-squared test and Student's t-test were used to assess the difference between OM and any other metastasis (NOM). Receiver operating curve (ROC) was used to analyze the diagnostic value of serum biomarkers in HCC patients with OM. Results: The incidence of OM in HCC patients was 1.88% in our research. There are no significant differences in age, gender, or histopathology in the OM group and the group without any metastasis. Binary logistic regression analysis presented that compared with the patients without cancer metastasis, carbohydrate antigen 125 (CA-125) and hemoglobin (Hb) were risk factors in hepatocellular carcinoma patients with OM (P < 0.05). The ROC curve analysis showed that the areas under the CA-125, Hb, and CA125+Hb curves were 0.877, 0.554, and 0.431, and the cutoff values of CA-125 and Hb each were 115.78 u/mL and 120.50 g/L. Conclusion: Our data suggest that CA-125 and Hb are risk indicators in hepatocellular carcinoma patients with OM, and that CA-125+Hb has potentially greater utility in diagnosing hepatocellular carcinoma.

Retinal microvasculature alteration in patients with systemic sclerosis and chloroquine treatment.

Background: Retinal vascular abnormality is an important part of ocular systemic sclerosis (SSc), and long-term use of chloroquine can lead to retinal toxicity. This study was conducted to evaluate retinal microvascular changes using optical coherence tomography angiography (OCTA) in patients with SSc and SSc patients on long-term chloroquine treatment. Methods: Fifteen SSc patients without chloroquine (30 eyes), 15 SSc patients taking long-term chloroquine (30 eyes) and 15 healthy controls (30 eyes) were recruited to this cross-sectional study. OCTA was used to examine the superficial and deep retinal capillary plexus in the macular retina of each eye. The densities of microvessels (MIR), macrovessels (MAR) and total microvessels (TMI) in the superficial and deep retina of the three groups were calculated and compared. We used the hemisphere segmentation method [superior right (SR), superior left (SL), inferior left (IL), and inferior right (IR)] and Early Treatment Diabetic Retinopathy Study (ETDRS) method [right (R), superior (S), left (L), and inferior (I)] to analyze changes in retinal microvascular density. Results: The superficial and deep retinal MIR density in SSc patients decreased (P<0.05) compared with the healthy control group. This significant difference was found in both superficial and deep layers in S, L, SR, SL and IL regions (P<0.05), and additionally in the R and I regions in the superficial layer (P<0.05). Similarly, compared with SSc patients who did not take chloroquine, the superficial and deep retinal MIR density of SSc patients on long-term chloroquine also decreased (P<0.05). This significant difference was found in both superficial and deep layers in R, I and IL regions (P<0.05), and additionally in the IR region in the superficial layer (P<0.05). Conclusions: The OCTA results suggest that retinal MIR density is decreased in SSc patients, and that long-term use of chloroquine will aggravate this damage, resulting in a further decrease in retinal MIR density.

AFP and CA-125 as an accurate risk factor to predict eye metastasis in hypertension patients with liver carcinoma: A STROBE-compliant article.

Purpose: In this study, we analyzed the differences between hypertension patients with ocular metastasis of liver cancer and those with metastases to other sites, the correlation between history of HBV and liver cancer metastasis, and independent risk factors for ocular metastasis. Methods: We used treatment records from 488 patients with metastases of primary liver cancer from August 2001 to May 2015, divided into two groups based on metastatic sites: OM (ocular metastasis) and NOM (non-ocular, other sites of metastasis) groups. The Student's t-test and Chi-square test were used to assess the significance of differences between the groups and define the relationship between history of HBV and ocular metastasis of liver cancer. Binary logistic regression analysis was used to identify indicators of ocular metastasis of liver cancer and receiver operating curve (ROC) analyses to estimate their diagnostic value. Results: No significant differences in sex, age, tumor stage, pathological type, or treatment were identified between the OM and NOM groups, while the prevalence of HBV was higher in the former than that in latter. Binary logistic regression demonstrated that AFP and CA-125 were independent indicators of liver metastasis (both p < 0.001). ROC curve analyses generated cut-off values for AFP and CA-125 of 957.2 ng/ml and 114.25 U/ml, respectively, with corresponding AUC values of 0.739 and 0.810. The specificity of the combination of AFP and CA-125 was higher than either factor separately. Discussion: To explore the diagnostic value of AFP and CA125 in predicting the development of ocular metastases of hypertensive patients with liver cancer, which will help us to diagnose the occurrence and development of the disease more accurately and make the best clinical diagnosis and treatment measures.

Potential factors of cytokeratin fragment 21-1 and cancer embryonic antigen for mediastinal lymph node metastasis in lung cancer.

Objective: Lung cancer is a common malignant tumor, characterized by being difficult to detect and lacking specific clinical manifestations. This study aimed to find out the risk factors of mediastinal lymph node metastasis and explore the correlation between serum tumor markers and mediastinal lymph node metastasis and lung cancer prognosis. Methods: A retrospective study of 3,042 lung cancer patients (330 patients with mediastinal lymph node metastasis and 2,712 patients without mediastinal lymph node metastasis) collected from the First Affiliated Hospital of Nanchang University from April 1999 to July 2020. The patients were divided into two groups, namely, mediastinal lymph node metastasis group and non-mediastinal lymph node metastasis group. Student's t test, non-parametric rank sum test and chi-square test were used to describe whether there is a significant difference between the two groups. We compared the serum biomarkers of the two groups of patients, including exploring serum alkaline phosphatase (ALP), calcium hemoglobin (HB), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA125, CA-199, CA -153, cytokeratin fragment 19 (CYFRA 21-1), total prostate specific antigen (TPSA), neuron-specific enolase (NSE) levels and the incidence and prognosis of lung cancer mediastinal lymph node metastasis. Binary logistic regression analysis was used to determine its risk factors, and receiver operating curve (ROC) analysis was used to evaluate its diagnostic value for mediastinal lymph node metastasis. Results: Binary logistic regression analysis showed that carcinoembryonic antigen and CYFRA 21-1 were independent risk factors for mediastinal lymph node metastasis in patients with lung cancer (p < 0.001 and p = 0.002, respectively). The sensitivity and specificity of CEA for the diagnosis of mediastinal lymph node metastasis were 90.2 and 7.6%, respectively; CYFRA 21-1 were 0.6 and 99.0%, respectively. Conclusion: Serum CEA and CYFRA 21-1 have predictive value in the diagnosis of mediastinal lymph node metastasis in patients with lung cancer.

Altered Spontaneous Brain Activity Patterns in Children With Strabismic Amblyopia After Low-Frequency Repetitive Transcranial Magnetic Stimulation: A Resting-State Functional Magnetic Resonance Imaging Study.

Objective: Previous studies have demonstrated altered brain activity in strabismic amblyopia (SA). In this study, low-frequency repetitive transcranial magnetic stimulation (rTMS) was applied in children with strabismic amblyopia after they had undergone strabismus surgery. The effect of rTMS was investigated by measuring the changes of brain features using the amplitude of low-frequency fluctuation (ALFF). Materials and Methods: In this study, 21 SA patients (12 males and 9 females) were recruited based on their age (7-13 years old), weight, and sex. They all had SA in their left eyes and they received rTMS treatment one month after strabismus surgery. Their vision before and after surgery were categorized as pre-rTMS (PRT) and post-rTMS (POT). All participants received rTMS treatment, underwent magnetic resonance imaging (MRI), and their data were analyzed using the repeated measures t-test. The team used correlation analysis to explore the relationship between logMAR visual acuity and ALFF. Results: Pre- versus post-rTMS values of ALFF were significantly different within individuals. In the POT group, ALFF values were significantly decreased in the Angular_R (AR), Parietal_Inf_L (PIL), and Cingulum_Mid_R (CMR) while ALFF values were significantly increased in the Fusiform_R (FR) and Frontal_Inf_Orb_L(FIL) compared to the PRT stage. Conclusion: Our data showed that ALFF recorded from some brain regions was changed significantly after rTMS in strabismic amblyopes. The results may infer the pathological basis of SA and demonstrate that visual function may be improved using rTMS in strabismic amblyopic patients.

Ocular microvascular alteration in Sjögren syndrome.

BACKGROUND: Sjögren syndrome (SjS) is a systemic disease affecting exocrine, including ocular lacrimal, glands. It is uncertain whether ocular microvascular alterations are associated with this disease. In this study, we evaluated retinal and conjunctival microvascular changes in SjS patients using optical coherence tomography angiography (OCTA). METHODS: Twelve SjS patients (24 eyes) and 12 normal controls (24 eyes) were recruited to this study. Three-dimensional conjunctival and retinal OCTA images of each eye were captured and microvascular density was calculated. Each image was analyzed by retinal area based on the early treatment of diabetic retinopathy study method (R, S, L, and I) hemisphere segmentation method (SR, SL, IL, and IR); and central wheel division method (C1-C6). Correlation analyses were used to look for associations between retinal and conjunctival microvascular densities. RESULTS: Superficial and deep retinal layer microvascular density was decreased in SjS patients compared with normal controls (P<0.05). This significant difference was found in both superficial and deep layers in S, L, SL, IL and C1-C3 regions, and additionally in the I and SR regions in the superficial layer. Conversely, in the conjunctiva microvascular density was higher in SjS patients than in controls. In SjS patients, a significant negative correlation was found between conjunctival and both superficial (r=-0.641; P=0.025) and deep (r=-0.958; P<0.0001) microvascular densities. CONCLUSIONS: The changed microvascular densities measured in deep and superficial retinal layers and in the conjunctiva demonstrate that OCTA is a promising method in differentiating the eyes from those with SjS.

Clinical Significance of CYFRA21-1, AFP, CA-153, CEA, and CA-199 in the Diagnosis of Lung Cancer Ocular Metastasis in Hypertension Population.

Purpose: To detect lung metastases, we conducted a retrospective study to improve patient prognosis. Methods: Hypertension patients with ocular metastases (OM group; n = 58) and without metastases (NM group; n = 1,217) were selected from individuals with lung cancer admitted to our hospital from April 2005 to October 2019. The clinical characteristics were compared by Student's t-test and chi-square test. Independent risk factors were identified by binary logistic regression, and their diagnostic value evaluated by receiver operating characteristic curve analysis. Results: Age and sex did not differ significantly between OM and NM groups; There were significant differences in pathological type and treatment. Adenocarcinoma was the main pathological type in the OM group (67.24%), while squamous cell carcinoma was the largest proportion (46.43%) in the NM group, followed by adenocarcinoma (34.10%). The OM group were treated with chemotherapy (55.17%), while the NM group received both chemotherapy (39.93%) and surgical treatment (37.06%). Significant differences were detected in the concentrations of cancer antigen (CA)-125, CA-199, CA-153, alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), cytokeratin fraction 21-1 (CYFRA21-1), total prostate-specific antigen, alkaline phosphatase, and hemoglobin (Student's t-test). Binary logistic regression analysis indicated that CA-199, CA-153, AFP, CEA, and CYRFA21-1 were independent risk factors for lung cancer metastasis. AFP (98.3%) and CEA (89.3%) exhibited the highest sensitivity and specificity, respectively, while CYRFA21-1 had the highest area under the ROC curve value (0.875), with sensitivity and specificity values of 77.6 and 87.0%, respectively. Hence, CYFRA21-1 had the best diagnostic value.

Serum markers change for intraocular metastasis in renal cell carcinoma.

OBJECTIVE: Renal cell carcinoma is prone to early metastasis. In general, intraocular metastasis (IOM) is not common. In the present study, we studied the relationship between different biochemical indicators and the occurrence of IOM in renal cancer patients, and identified the potential risk factors. METHODS: A retrospective analysis of the clinical data of 214 patients with renal cell carcinoma from October 2001 to August 2016 was carried out. The difference and correlation of various indicators between the two groups with or without IOM was analyzed, and binary logistic regression analysis was used to explore the risk factors of IOM in renal cancer patients. The diagnostic value of each independent related factor was calculated according to the receiver operating curve (ROC). RESULTS: The level of neuron-specific enolase (NSE) in renal cell carcinoma patients with IOM was significantly higher than that in patients without IOM (P<0.05). There was no significant difference in alkaline phosphatase (ALP), hemoglobin (Hb), serum calcium concentration, α fetoprotein (AFP), carcinoembryonic antigen (CEA), CA-125 etc. between IOM group and non-IOM (NIOM) group (P>0.05). Binary logistic regression analysis showed that NSE was an independent risk factor for IOM in renal cell carcinoma patients (P<0.05). ROC curve shows that the factor has high accuracy in predicting IOM, and the area under the curve (AUC) is 0.774. The cut-off value of NSE was 49.5 U/l, the sensitivity was 72.2% and the specificity was 80.1%. CONCLUSION: NSE concentration is a risk factor for IOM in patients with renal cell cancer. If the concentration of NSE in the patient's body is ≥49.5 U/l, disease monitoring and eye scans should be strengthened.

Alternation of brain intrinsic activity in patients with hypertensive retinopathy: a resting-state fMRI study.

OBJECTIVE: To investigate the changes of amplitude of low-frequency fluctuation (ALFF) in brain regions of patients with hypertensive retinopathy by using resting-state functional magnetic resonance imaging (rs-fMRI) and change in the relationship of ALFF value with potential emotional and psychological changes. METHODS: Thirty-one patients with hypertensive retinopathy (HR) (16 men and 15 women) and 31 healthy controls (HCs; 16 men and 15 women) matched for age, sex, and weight were enrolled in the research. The changes in mean ALFF values could reflect brain activity between HR patients and HCs. We used the independent samples t-test to evaluate different demographic and general information between the two groups. Two-sample t-test was used to detect differences of mean ALFF values in the brain region between the two groups using the same software. RESULTS: The ALFF values in the brain areas of HR and HCs were different. HR patients had lower ALFF value in the left medial superior frontal gyrus and left middle frontal gyrus than the HCs. The higher ALFF values were found in the cerebellum (left inferior and right superior lobes, vermis) and left inferior temporal gyrus of the HR patients than the controls. CONCLUSION: Our findings showed fluctuations in ALFF values in the HR patients' brain regions. ALFF values reflect over or reduced activity in brain regions. Abnormal ALFF values in these brain areas can predict early HR development, preventing the malignant transformation of hypertensive microangiopathy.

Risk Factors and Their Diagnostic Values for Ocular Metastases in Gastric Adenocarcinoma.

OBJECTIVE: Gastric adenocarcinoma originates from the glands in the superficial layer or mucosa of the stomach. It is prone to metastases, of which ocular metastasis (OM) is rare, but once it occurs the disease is considered more serious. The aim of this study was to investigate the risk factors for OM in gastric adenocarcinoma. METHODS: Patients with gastric adenocarcinoma were recruited to this study between June 2003 and July 2019. Demographic data and serological indicators (SI) were compared between patients with and without OM, and binary logistic regression was used to explore whether the relevant SI may be risk factors for OM of gastric adenocarcinoma. Receiver operating characteristic (ROC) curves were used to analyze different SIs for OM in gastric cancer patients. RESULTS: Chi-square tests showed significant between-groups difference in gender composition (P < 0.05), but not in age or histological grade (P > 0.05). t-test results showed that low-density lipoprotein (LDL) and carbohydrate antigen-724 (CA724) were significantly higher in patients with than without OM (P < 0.05). Binary logistic regression analysis showed that LDL was an independent risk factor for OM (P < 0.001). ROC curve analysis showed that the areas under the curves (AUC) for LDL and CA724 were 0.903 and 0.913 respectively, with higher AUC for combined LDL and CA724 (0.934; P < 0.001). CONCLUSION: LDL and CA724 have value as predictors for OM in patients with gastric adenocarcinoma, with higher predictive value when these factors are combined.

Risk factors for intraocular metastasis of primary liver cancer in diabetic patients: Alpha-fetoprotein and cancer antigen 125.

BACKGROUND: In rare instances, primary liver cancer can be associated with intraocular metastasis (IOM). AIM: To investigate the correlation between a diverse range of clinical characteristics and IOM in diabetic patients with primary liver cancer, and to determine potential risk factors in predicting IOM. METHODS: We recruited a total of 722 diabetic patients with primary liver cancer. The differences between the IOM and non-intraocular metastasis (NIOM) groups in these patients were assessed using the chi-squared test and Student's t-test. Binary logistic regression analysis was subsequently used to determine risk factors. Finally, the diagnostic value of IOM in this cohort with primary liver cancer was analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS: In all, 13 patients had IOM. There were no remarkable intergroup differences with respect to age, sex, histopathological sub-types, or blood biochemical parameters. However, the IOM group had significantly higher alpha-fetoprotein (AFP) and cancer antigen 125 (CA125) values than the NIOM group. Binary logistic regression identified AFP and CA125 to be significant risk factors for IOM in diabetic patients with primary liver cancer. ROC curve analysis showed that the area under the curve values for AFP and CA125 were 0.727 and 0.796, with the cut-off values of 994.20 ng/mL and 120.23 U/mL, respectively. The sensitivity and specificity for AFP were 92.3% and 59.9%, while those for CA125 were 84.6% and 70.1%, respectively. CONCLUSION: Elevated AFP and CA125 represent significant risk factors for IOM in diabetic patients with primary liver cancer.

Risk factors and their diagnostic values for ocular metastases in invasive ductal carcinoma.

Invasive ductal carcinoma (IDC) is a major type of breast cancer. Ocular metastasis (OM) in IDC is rarely seen, but patients with OM often have a poor prognosis. Furthermore, OM is difficult to detect in the early stages by common imaging examinations. In the present study, we tried to figure out the risk factors of OM in IDC and evaluate their diagnostic values for early detection. There were 1192 IDC patients who were divided into two groups according to ocular metastasis involved in this study. Clinical parameters of those patients were used to detect differences. The binary logistic regression test was then used to determine the risk factors of OM in IDC. Furthermore, ROC curves of both single and combined risk factors were established to examine their diagnostic values. The incidence of axillary lymph node metastases was significantly higher in the OM group (p = 0.002). Higher carbohydrate antigen 153 (CA153), lower apolipoprotein A1 (ApoA1), and hemoglobin (Hb) were risk factors for OM in IDC (p < 0.001, p < 0.001, p = 0.038, respectively). In the single risk factor ROC analysis, cutoff values of CA153, ApoA1, and Hb were 43.3 u/mL (CI: 0.966-0.984, p < 0.001), 1.11 g/L (CI: 0.923-0.951, p < 0.001), and 112 g/L (CI: 0.815-0.857, p < 0.001), respectively. Among the ROC curves of combined risk factors, CA153+ApoA1+Hb had the best accuracy, with the sensitivity and specificity of 89.47% and 99.32%, respectively (CI: 0.964-0.983, p < 0.001). CA153, ApoA1, and Hb are risk factors for OM in IDC. In clinical practice, the three parameters could be used as predictive factors for the early detection of OM.

Evaluation of PTEN and CD4+FOXP3+ T cell expressions as diagnostic and predictive factors in endometrial cancer: A case control study.

To evaluate the potential role of Pten and CD4FOXP3 T cells in prognosis from endometrial cancer.Tissue samples and clinical data were collected from 200 patients with endometrial cancer and 100 control patients with benign uterine diseases. The expressions of Pten and CD4FOXP3 T cells were quantified by immunohistochemistry and immunofluorescence. After surgery, all patients were followed up for an average of 56.3 months. Surgical effects were evaluated based on the patients' symptoms and signs. A two-sided P value < .05 was considered significant.Pten diminished and CD4FOXP3 T cells significantly accumulated with the progression of endometial cancer, in comparison to the controls. Moreover, Pten expression was negatively correlated with the count of CD4FOXP3 T cells. Pten and CD4FOXP3 T cells were correlated with clinical characteristics, including tumor stage, differentiation and associated with patients' disease-free survival.Limited data were available between the expressions of Pten and CD4FOXP3 T cells in patients with endometrial cancer. Our study findings suggested that the expressions of Pten and CD4FOXP3 T cells might become possible biomarkers for the diagnosis and prediction in endometrial cancer.

Anti-inflammatory effect of a curcumin-aspirin derivative on Ureaplasma-induced cytokine expressions in neonatal monocytes.

One of the major contributors to death in infants is infant respiratory distress syndrome (IRDS). The transition from early acute inflammation to fibrotic hyperplasia is important in the development of IRDS. However, there are no available and effective remedies for suppression of the early inflammation. In this study, the effect of a curcumin-aspirin (C-A) derivative on the expressions of interleukin (IL)-10, IL-8, tumor necrosis factor (TNF)-α, IL-1ß, toll-like receptor (TLR)4 and TLR2 was investigated in neonatal monocytes exposed to Ureaplasma parvum. The techniques used were qPCR and flow cytometry. The results revealed that C-A exerted anti-inflammatory effects on stimulated monocytes and significantly suppressed Ureaplasma-stimulated changes in IL-8, TNF-α and IL-1ß levels. It did not produce any inflammation or apoptosis in the neonatal cells. Moreover, C-A enhanced IL-10 expression and suppressed the expressions of TLR2 and TLR4, indicating that curcumin-aspirin derivative might hold therapeutic potential for early IRDS.