Assessment of left ventricular myocardial work done by noninvasive pressure-strain loop technique in patients with essential hypertension.

OBJECTIVE: To investigate the value of the noninvasive pressure-strain loop (PSL) technique for assessing left ventricular myocardial work done in patients with essential hypertension. METHODS: Prospectively, 60 patients with hypertension visiting the hospital from August 2020 to July 2021 were collected and divided into the mild hypertension group (SBP 140-159 mmHg, 35 cases) and the moderate-to-severe hypertension group (SBP ≥160 mmHg, 25 cases). Another 40 cases of healthy adults were collected as the control group. The differences in the global long-axis strain (GLS) and peak strain dispersion (PSD) of the left ventricle, global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were compared among the three groups. The receiver operating characteristic curve was used to evaluate the PSD, GWI, GCW, and GWW. The myocardial work index (MWI) and MWI percentages in the apical, middle, and basal segments of the heart were also compared among the groups. RESULTS: (1) The PSD, GWI, GCW, and GWW were significantly different among the groups (Χ2  = 57.605, 79.203, 76.973, and 17.429, respectively, p < .05), while the GLS and GWE were not (Χ2  = 1.559 and 5.849, respectively, p > .05). (2) The GWI had the highest specificity (97.5%) and the GCW the highest sensitivity (95%) in predicting hypertension. The percentage of apical MWI gradually increased (F = 11.230, p < .05) and the percentage of basal MWI gradually decreased (F = 10.665, p < .05) from the control group to the mild hypertension group to the moderate-to-severe hypertension group; there was no significant difference in the percentage of mid-MWI (F = 0.593, p > .05). CONCLUSIONS: The noninvasive PSL technique could be used to assess myocardial work done in patients with essential hypertension.

Activation of C3 and C5 May Be Involved in the Inflammatory Progression of PCM and GM.

Plasma cell mastitis (PCM) and granulomatous mastitis (GM) are the most common inflammatory diseases constituting nonbacterial mastitis (NBM). However, the pathogenesis of NBM remains unclear. In this study, risk factors for NBM were assessed, as well as the pathological features of PCM and GM. The levels of C3/C3a-C3aR and C5/C5a-C5aR1 of tissues were detected by IHC and WB. Exosomes were isolated from serum and identified by transmission electron microscopy. Then, C3 and C5 levels were detected in peripheral blood, and exosomes were assessed by flow cytometry and immunoelectron microscopy. Obesity and prolonged lactation were risk factors for NBM. The infiltration of plasma cells and lymphocytes around the dilated catheter in PCM and the formation of granulomatous structures in GM were the respective pathological features. C3/C3a-C3aR and C5/C5a-C5aR1 levels were elevated in PCM and GM tissue samples. There were no differences in peripheral blood levels of C3 and C5, while C3a and C5a were highly expressed in exosomes. These results suggest that the complement family is activated in PCM and GM, exosomes enrich C3a and C5a, and mediate the spread of inflammation. These findings provide new insights into the molecular mechanisms of PCM and GM and identify therapeutic targets.

Value of Contrast-Enhanced Ultrasound in Adjusting the Classification of Chinese-TIRADS 4 Nodules.

OBJECTIVES: To explore the value of applying contrast-enhanced ultrasound (CEUS) in adjusting the classification of category 4 nodules in the Chinese-Thyroid Imaging Report and Data System (C-TIRADS). METHODS: The data of preoperative conventional ultrasound and CEUS examinations of 125 C-TIRADS 4 nodules in 109 patients were retrospectively analyzed. We divided the thyroid nodules into two groups based on whether recommend by the guide fine-needle aspiration (FNA). Group I included C-TIRADS 4A nodules with a maximum diameter ≤15 mm and C-TIRADS 4B and 4C nodules with a maximum diameter ≤10 mm, and Group II included C-TIRADS 4A nodules with a maximum diameter >15 mm and C-TIRADS 4B and 4C nodules with a maximum diameter >10 mm. In CEUS, thyroid nodules showing suspicious malignant features such as hypoenhancement or early washout were adjusted to a level higher in the C-TIRADS classification; thyroid nodules showing possible benign features such as iso- or hyperenhancement were adjusted to a level lower; and thyroid nodules showing no enhancement were adjusted to C-TIRADS 3. Taking the pathological results as the gold standard, the receiver operating characteristic (ROC) curves of the C-TIRADS classification before and after the adjustment based on CEUS were plotted, and the diagnostic efficiency was compared. RESULTS: The sensitivity, specificity, accuracy, and positive and negative predictive values of the C-TIRADS classification for the diagnosis of thyroid nodule malignancy before the adjustment based on the CEUS results were 83.6%, 63.8%, 74.4%, 72.7%, and 77.1%, respectively, and these values were 91.0%, 82.8%, 87.2%, 85.9%, and 88.9%, respectively, after the adjustment. The area under the ROC curve (AUC) was 0.737 and 0.869, respectively, showing a significant difference (Z = 3.288, P=0.001). The diagnostic efficiency of C-TIRADS classification after the adjustment based on the CEUS results in both groups was improved compared with the result before the adjustment, and the difference in Group II was significant (Z = 2.931, P=0.003). CONCLUSIONS: CEUS significantly improved the diagnostic performance in the adjustment of C-TIRADS 4 nodule classification, especially for the nodules which needs FNA recommended by the C-TIRADS.

Value of three-section contrast-enhanced transrectal ultrasonography in the detection of prostate cancer.

BACKGROUND: To assess the efficacy of three-section contrast-enhanced transrectal ultrasonography (CETRUS) in prostate cancer (PCa) detection. METHODS: A total of 169 consecutive patients with either PSA level ≥ 4 ng/ml or abnormal digital rectal examination findings were prospectively enrolled in this single center study. All patients underwent baseline transrectal ultrasonography (TRUS) and three-section CETRUS by one investigator blinded to any clinical data before TRUS-guided transperineal biopsy. The performances of baseline TRUS, single-section, and three-section CETRUS for PCa detection were compared. RESULTS: On a per-patient basis, the sensitivity, specificity, and overall accuracy for detecting PCa with three-section CETRUS was 92.3%, 69.2%, and 78.1%, respectively. In comparison with conventional (single-section) CETRUS (sensitivity 75.4%, specificity 72.1%, and accuracy 73.4%), three-section CETRUS performed significantly better (p < 0.05, McNemar test). Additionally, the low-grade PCa detection rate for three-section CETRUS was significantly higher than that of conventional CETRUS (26.7% versus 10.2%, p < 0.05). CONCLUSIONS: Our study demonstrated a significant benefit of three-section CETRUS relative to conventional CETRUS, and this technique may find more PCa patients eligible for active surveillance. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:304-309, 2017.

Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma.

Chromodomain helicase DNA binding protein 5 (CHD5) acts as a tumor suppressor in many cancers. In the present study, we demonstrated that reduced levels of CHD5 in hepatocellular carcinoma (HCC) tissues were significantly associated with metastasis and poor prognosis. Gain-of-function assays revealed that CHD5 suppressed motility and invasion of HCC cells. Subsequent investigations showed that CHD5 was epigenetically silenced by polycomb repressive complex 2 (PRC2)-mediated the trimethylation of histone H3 at lysine 27 (H3K27me3) in HCC cells. Furthermore, overexpression of CHD5 repressed enhancer of zeste homolog 2 (EZH2) and activated PRC2 target genes, such as p16 and p21. Chromatin immunoprecipitation and luciferase reporter assays also showed that CHD5 and EZH2 bind to each other's promoters and inhibit transcription. These findings uncovered, for the first time, a mutual suppression regulation between CHD5 and EZH2, which may provide new insights into their potential therapeutic significance for HCC.

Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma.

DLC1 has been shown to be downregulated or absent in hepatocellular carcinoma (HCC) and is associated with tumorigenesis and development. However, only a small number of studies have focused on genetic variations of DLC1. The present study performed exon sequencing for the DLC1 gene in HCC tissue samples from 105 patients to identify functional genetic variation of DLC1 and its association with HCC susceptibility, clinicopathological features and prognosis. A novel missense mutation and four non­synonymous single nucleotide polymorphisms (SNPs; rs3816748, rs11203495, rs3816747 and rs532841) were identified. A significant correlation of rs3816747 polymorphisms with HCC susceptibility was identified. Compared to individuals with the GG genotype of rs3816747, those with the GA (odds ratio (OR)=0.486; P=0.037) or GA+AA genotype (OR=0.51; P=0.039) were associated with a significantly decreased HCC risk. Furthermore, patients with the GC+CC genotype of rs3816748, the TC+CC genotype of rs11203495 or the GA+AA genotype of rs3816747 had small­sized tumors compared with those carrying the wild­type genotype. No significant association of DLC1 SNPs with the patients' prognosis was found. These results indicated that genetic variations in the DLC1 gene may confer a risk for HCC.

Intercellular adhesion molecule-1 inhibits osteogenic differentiation of mesenchymal stem cells and impairs bio-scaffold-mediated bone regeneration in vivo.

Mesenchymal stem cell (MSC) loaded bio-scaffold transplantation is a promising therapeutic approach for bone regeneration and repair. However, growing evidence shows that pro-inflammatory mediators from injured tissues suppress osteogenic differentiation and impair bone formation. To improve MSC-based bone regeneration, it is important to understand the mechanism of inflammation mediated osteogenic suppression. In the present study, we found that synovial fluid from rheumatoid arthritis patients and pro-inflammatory cytokines including interleukin-1α, interleukin-1ß, and tumor necrosis factor α, stimulated intercellular adhesion molecule-1(ICAM-1) expression and impaired osteogenic differentiation of MSCs. Interestingly, overexpression of ICAM-1 in MSCs using a genetic approach also inhibited osteogenesis. In contrast, ICAM-1 knockdown significantly reversed the osteogenic suppression. In addition, after transplanting a traceable MSC-poly(lactic-co-glycolic acid) construct in rat calvarial defects, we found that ICAM-1 suppressed MSC osteogenic differentiation and matrix mineralization in vivo. Mechanistically, we found that ICAM-1 enhances MSC proliferation but causes stem cell marker loss. Furthermore, overexpression of ICAM-1 stably activated the MAPK and NF-κB pathways but suppressed the PI3K/AKT pathway in MSCs. More importantly, specific inhibition of the ERK/MAPK and NF-κB pathways or activation of the PI3K/AKT pathway partially rescued osteogenic differentiation, while inhibition of the p38/MAPK and PI3K/AKT pathway caused more serious osteogenic suppression. In summary, our findings reveal a novel function of ICAM-1 in osteogenesis and suggest a new molecular target to improve bone regeneration and repair in inflammatory microenvironments.