Association Between Plasma Levels of ANGPTL3, 4, 8 and the Most Common Additional Cardiovascular Risk Factors in Patients with Hypertension.

Background: ANGPTL3, 4 and 8 have been reported to be involved in the regulation of lipid and glucose metabolism. The aim of this study was to investigate the expression of ANGPTL3, 4, 8 in hypertensive patients with or without overweight/obesity, T2D, and hyperlipidemia, and the possible association between their expression and the status of the aforementioned comorbidities. Methods: Plasma levels of ANGPTL3, 4, and 8 in 87 hospitalized patients with hypertension were measured using ELISA kits. Associations between circulating ANGPTLs levels and the most common additional cardiovascular risk factors were assessed using multivariate linear regression analyses. Pearson's correlation analysis was used to examine the association between ANGPTLs and clinical parameters. Results: In the context of hypertension, (1) although not statistically significant, circulating ANGPTL3 levels were higher in the overweight/obese group than in the normal weight group; (2) circulating levels of ANGPTL3 and ANGPTL8 were significantly lower in patients with T2D than in non-diabetic patients; (3) circulating ANGPTL3 levels were significantly higher in the hyperlipidemic group than in the non-hyperlipidemic group. ANGPTL3 was associated with T2D and hyperlipidemia status, whereas ANGPTL8 was independently associated with T2D status. In addition, circulating ANGPTL3 levels were positively correlated with TC, TG, LDL-C, HCY, and ANGPTL8, and circulating ANGPTL4 levels were positively correlated with UACR and BNP. Conclusion: Changes in circulating ANGPTL3 and ANGPTL8 levels have been observed in hypertensive patients with the most common additional cardiovascular risk factors, suggesting a role in the common comorbidities of hypertension and cardiovascular disease. Hypertensive patients with overweight/obesity or hyperlipidemia may benefit from therapies targeting ANGPTL3.

Association of Clinical Features of Colorectal Cancer with Circulating Tumor Cells and Systemic Inflammatory Markers.

Background: Circulating tumor cells (CTCs) in peripheral blood have been shown to reflect the prognosis of patients with colorectal cancer, and epithelial and mesenchymal markers further predict the likelihood of cancer dissemination. This study was conducted to identify possible association of clinical features of colorectal cancer with CTC counts, their subtypes, and systemic inflammatory markers. Methods: Blood samples of 316 colorectal cancer patients were used for CTC detection and subtyping with EpCAM, CK8/18/19, vimentin, and twist as biomarkers. The neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, C-reactive protein/albumin ratio, lymphocyte/monocyte ratio, and systemic immune-inflammation index (SII) were also measured. The relationship between clinical data and these markers or parameters was analyzed. Results: Total CTC counts were correlated with whether there was lymph node involvement but was not correlated with TNM staging. There was a difference in mesenchymal CTCs between patients with and without lymph node involvement (P < 0.05). Also, more patients with metastasis tested positive for mesenchymal CTCs (P < 0.05). Of the systemic inflammatory markers, platelet/lymphocyte ratio was positively correlated with CTC counts (P < 0.01), and lymphocyte/monocyte ratio was negatively correlated with CTC counts (P < 0.05). Conclusions: Colorectal cancer patients with the mesenchymal markers on their CTCs are more likely to have lymph node involvement or distant metastasis than those without these markers.

Characterization of E-cadherin expression in normal mucosa, dysplasia and adenocarcinoma of gastric cardia and its influence on prognosis.

BACKGROUND: Gastric cardia adenocarcinoma (GCA), which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries, is of similar geographic distribution with esophageal squamous cell carcinoma in China, and even referred as "sister cancer" by Chinese oncologists. The molecular mechanism for GCA is largely unknown. Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers. However, the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis. AIM: To characterize E-cadherin expression in normal gastric cardia mucosa, dysplasia and GCA tissues, and its influence on prognosis for GCA. METHODS: A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases. The enrollment criteria included radical surgery for GCA, but without any radio- or chemo-therapy before operation. The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue (n = 208) and dysplasia lesions (n = 156) were collected, and processed as tissue microarray for immunohistochemistry. The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter, telephone or home interview. E-cadherin protein expression was determined by two step immunohistochemistry. Kaplan-Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients. RESULTS: Of the 4561 GCA patients, there were 3607 males with a mean age of 61.6 ± 8.8 and 954 females with a mean age of 61.9 ± 8.6 years, respectively. With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA, the positive immunostaining rates for E-cadherin decreased significantly from 100% to 93.0% and 84.1%, respectively (R2 = 0.9948). Furthermore, E-cadherin positive immunostaining rate was significantly higher in patients at early stage (0 and I) than in those at late stage (II and III) (92.7% vs 83.7%, P = 0.001). E-cadherin positive expression rate was significantly associated with degree of differentiation (P = 0.001) and invasion depth (P < 0.001). Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative (P = 0.026). It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis. However, in patients with negative lymph node metastasis, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.036). Similarly, in patients with late stage GCA, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.011). CONCLUSION: E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.

Development and validation of a prognostic nomogram model for Chinese patients with primary small cell carcinoma of the esophagus.

BACKGROUND: Primary small cell carcinoma of the esophagus (PSCE) is a highly invasive malignant tumor with a poor prognosis compared with esophageal squamous cell carcinoma. Due to the limited samples size and the short follow-up time, there are few reports on elucidating the prognosis of PSCE, especially on the establishment and validation of a survival prediction nomogram model covering general information, pathological factors and specific biological proteins of PSCE patients. AIM: To establish an effective nomogram to predict the overall survival (OS) probability for PSCE patients in China. METHODS: The nomogram was based on a retrospective study of 256 PSCE patients. Univariate analysis and multivariate Cox proportional hazards regression analysis were used to examine the prognostic factors associated with PSCE, and establish the model for predicting 1-, 3-, and 5-year OS based on the Akaike information criterion. Discrimination and validation were assessed by the concordance index (C-index) and calibration curve and decision curve analysis (DCA). Histology type, age, tumor invasion depth, lymph node invasion, detectable metastasis, chromogranin A, and neuronal cell adhesion molecule 56 were integrated into the model. RESULTS: The C-index was prognostically superior to the 7th tumor node metastasis (TNM) staging in the primary cohort [0.659 (95%CI: 0.607-0.712) vs 0.591 (95%CI: 0.517-0.666), P = 0.033] and in the validation cohort [0.700 (95%CI: 0.622-0.778) vs 0.605 (95%CI: 0.490-0.721), P = 0.041]. Good calibration curves were observed for the prediction probabilities of 1-, 3-, and 5-year OS in both cohorts. DCA analysis showed that our nomogram model had a higher overall net benefit compared to the 7th TNM staging . CONCLUSION: Our nomogram can be used to predict the survival probability of PSCE patients, which can help clinicians to make individualized survival predictions.

Effects of a Caregiver Training Program on Oral Hygiene of Alzheimer's Patients in Institutional Care.

OBJECTIVES: To investigate the effects of a caregiver training program on the oral hygiene of caregivers and patients with Alzheimer's disease (AD) and to identify program components and parameters for accurate assessment of outcomes. DESIGN: Single-blinded prospective cohort study. SETTING AND PARTICIPANTS: Patients with AD and caregivers in nursing homes in the Greater Zhengzhou Area, China. METHODS: Initially 168 AD patient/caregiver pairs were recruited and randomly assigned to control, limited training, and comprehensive training groups. The mini-mental state examination, global deterioration scale, and Katz activities of daily living scale were conducted for patients with AD. Information on participants' oral hygiene habits and general oral health was collected. The modified Quigley-Hein Plaque Index (PI) and Gingival Index (GI) were used to assess oral hygiene and gingival health. Intervention included (1) an educational video showing the role of dental plaque and the modified Bass technique; and (2) caregivers practicing toothbrushing on themselves and patients with AD under professional guidance. Changes in oral hygiene and correlations between patient PI/GI and caregiver PI/GI were analyzed. RESULTS: After 6 weeks, complete data for 146 AD patient/caregiver pairs were collected. Before enrollment, most patients with AD had very poor oral hygiene. Compared with controls and limited training, only comprehensive training was able to achieve steady reduction in PI and GI scores in patients with AD, which still fell short of desirable levels (PI: 2.46 ± 0.52, GI: 1.24 ± 0.24, week 6). PI and GI scores in caregivers saw steady improvement only through comprehensive training (PI: 1.41 ± 0.38, GI: 0.88 ± 0.19, week 6). Number of training sessions had the greatest influence on both patient PI and GI scores. CONCLUSIONS AND IMPLICATIONS: Comprehensive caregiver training on toothbrushing skills is effective in improving the oral hygiene of caregivers and patients with AD in nursing homes. Additional evidence is needed to establish the optimal program structure.

Contribution of CYP24A1 variants in coronary heart disease among the Chinese population.

BACKGROUND: Cytochrome P450 (CYPs) participate in the mechanisms of cardiovascular disease. The purpose of this research was to evaluate the contributions of CYP24A1 variants to coronary heart disease (CHD) among the Chinese Han population. METHODS: This study included 505 CHD cases and 508 controls. Four variants of CYP24A1 (rs2762934, rs1570669, rs6068816 and rs2296241) were chosen and genotyped by the Agena MassARRAY system among the Chinese population. The linkage between CYP24A1 variants and CHD risk were assessed by logistic regression to compute the odds ratio (OR) and 95% confidence interval (CI). Then, multifactor dimensionality reduction (MDR) was applied to analyze the interactions of CYP24A1 variants. RESULTS: The results of this study showed that CYP24A1 rs6068816 significantly enhanced CHD risk in multiple genetic models (allele: P = 0.014; codominant: P = 0.015; dominant: P = 0.043; recessive: P = 0.040; additive: P = 0.013), whereas rs2296241 was likely to protect individuals from CHD (codominant: P = 0.019; recessive: P = 0.013; additive: P = 0.033). Stratification analysis revealed that CYP24A1 polymorphisms had strong relationships with CHD risk that were dependent on age, sex, Gensini grade and smoking status (P <  0.05). Moreover, a four-locus model (rs2762934, rs1570669, rs6068816 and rs2296241) had significant impact on CHD risk in MDR analysis. CONCLUSION: It revealed that CYP24A1 variants were significantly linked with CHD susceptibility in the Chinese population.

Evaluating and monitoring bone marrow hypoplasia in adults with aplastic anemia via high-resolution iliac magnetic resonance imaging in the current era.

The diagnosis and monitoring of aplastic anemia (AA) rely heavily on a complete blood count (CBC), and multiple-site bone marrow (BM) aspirations and biopsies. However, these approaches have certain limitations. We aimed to assess high-resolution magnetic resonance imaging (MRI) as a complementary approach for evaluating BM hypoplasia and monitoring treatment response in adults with AA in the current era.Twelve newly diagnosed AA patients and 12 sex- and age-matched healthy controls were enrolled in this study from January 2017 to August 2018. A bilateral iliac 3.0T MRI was used to collect data for each subject, and the signal intensity on the T1-weighted images (T1WIs) were expressed as a contrast-to-noise ratio (CNR). The MRI, CBC, and BM biopsy data were analyzed and compared.A qualitative analysis identified a significant difference in MRI signal characteristics between the AA group and the healthy control group. The clinical classifications of very severe aplastic anemia (VSAA) and severe aplastic anemia (SAA) corresponded to pattern I and pattern II on the MR images, respectively. However, this imaging classification did not correlate with the biopsy-based BM cellularity measure. A quantitative analysis showed a significantly higher signal intensity in AA patients than in controls. A within-group comparison revealed that more severe types of AA, based on the clinical classification, corresponded to stronger signals. Notably, MRI could detect treatment response earlier than CBC, regardless of whether there were improvements in hematopoiesis.MRI can be used to predict the therapeutic effects in patients with AA and is an important complementary tool for evaluating and monitoring BM hypoplasia.