Correlation of ultrasound features with Bcl-2 protein expression in basal cell carcinomas (BCCs).

BACKGROUND: The expression of the Bcl-2 protein is frequently observed in basal cell carcinomas (BCCs), making it a significant biological marker and potential therapeutic target. Skin ultrasonography offers a noninvasive means of obtaining anatomical information about cutaneous tumors. OBJECTIVES: The purpose of this study was to investigate the correlation between ultrasound features and Bcl-2 expression in BCCs, to provide a reference for developing pharmacological treatment plans. METHODS: According to the Bcl-2 protein expression, 74 BCCs confirmed by surgical pathology were divided into high Bcl-2 expression BCCs (HB-BCCs) and low Bcl-2 expression BCCs (LB-BCCs). Preoperative lesion ultrasound features were analyzed retrospectively based on Liang's criteria, which included the following features: shape, surface, keratinization, base, infiltration level, internal echogenicity, distribution of hyperechoic spots, posterior echogenic changes, internal Doppler signal, and lesion size (maximum diameter and infiltration depth). The differences of two groups were compared using a chi-square test or a paired t-test. RESULTS: Based on ultrasound features, cystic areas were more frequent in LB-BCCs (χ2 = 7.015, P = .008). Furthermore, LB-BCCs exhibited greater infiltration depth than HB-BCCs (4.86 ± 2.12 mm vs. 2.72 ± 1.40 mm, P = .000), had a higher propensity to infiltrate the subcutaneous tissue (χ2 = 12.422, P = .002), and displayed a more abundant internal Doppler signal within the lesions (χ2 = 24.696, P = .000). Conversely, maximum diameter of the lesions, shape, surface, keratinization, base, hyperechoic spots distribution, and posterior echogenic changes of the lesions did not differ significantly between the two groups. CONCLUSIONS: Ultrasound features are correlated with Bcl-2 protein expression level in BCCs. LB-BCCs show greater infiltration depth, subcutaneous infiltration, more cystic changes and more abundant internal Doppler signal than HB-BCCs, which may suggest a potential basis for drug selection in BCC chemotherapy.

Comparison of Sonographic Characteristics Between Superficial Basal Cell Carcinoma and Non-Superficial Basal Cell Carcinomas.

OBJECTIVES: To compare the sonographic characteristics of superficial basal cell carcinoma (sBCC) and non-superficial basal cell carcinomas (nsBCC). METHODS: The ultrasound characteristics of 73 basal cell carcinoma (BCC) confirmed by surgical pathology were retrospectively analyzed, and the cases were divided into 11 cases of sBCC and 62 cases of nsBCC according to pathological subtypes. Ultrasound characteristics between groups were compared. RESULTS: Among all the ultrasound characteristics, lesion thickness (P = .000), shape (χ2  = 39.293, P = .000), basal changes (χ2  = 8.473, P = .037), infiltration level (χ2  = 46.140, P = .000), and distribution of intralesional hyperechogenic spots (χ2  = 15.699, P = .000) of the lesions had statistically significant correlation with pathological diagnosis of sBCC. While no significant differences were shown in surface morphology, keratinization, maximum diameter, intralesional echogenicity, posterior echogenic changes, and intralesional color Doppler flow of the lesions. CONCLUSIONS: Small lesion thickness, oblate shape, superficial dermal local infiltration, and <3 internal hyperechogenic spots distribution of BCC determined by high frequency ultrasound may positively correlate with pathological diagnosis of sBCC. This is beneficial for treatment planning.

Usefulness of Shear Wave Elastography in Determining the Tumor Extent of Basal Cell Carcinomas.

OBJECTIVES: The purpose of this study was to investigate the value of shear wave elastography (SWE) in determining tumor extent of basal cell carcinomas (BCC), and thereby determine the optimal surgical margins (OSM). METHODS: 10 patients (40 surgical margins) with BCC were collected, the visual observation boundaries (VOB) were marked, and the SWE parameters of soft tissues were measured 1 mm intervals in "3, 6, 9, 12" clock directions, starting from VOB. Then tumors were resected with a 5 mm surgical margin outward expansion of VOB. All specimens were examined pathologically 1 mm intervals from VOB in four clock directions. With the positive margins furthest from the tumor as the real tumor boundaries (RTB) and the negative margins closest to the tumor as the optimal surgical margins (OSM). The SWE parameters were compared between these two groups. RESULTS: The elasticity ratio (Eratio ) of average young's modulus between region of interest and adjacent normal soft tissue had statistically significant differences between groups (P = .000), while other parameters show no difference. The Eratio of RTB and OSM were 1.22 ± 0.14 and 0.99 ± 0.07. The area under the ROC curve was .947. Taking 1.075 as the threshold of Eratio for the diagnosis of tumor extent, the sensitivity, specificity and accuracy were 87.5%, 90.0% and 90.0%. The surgical margins designed according to OSM were better than those designed according to VOB + 5 mm (P = .000). CONCLUSIONS: The Eratio of SWE is helpful in determining tumor extent of BCC. This is beneficial for surgical margin designing.

Clinical Prediction Nomograms to Assess Overall Survival and Disease-Specific Survival of Patients with Salivary Gland Adenoid Cystic Carcinoma.

Aim: Salivary gland adenoid cystic carcinoma (SACC) is the second highest incidence of malignant salivary gland tumor. The purpose of this study was to establish nomograms combined with SACC patients based on the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Patients with SACC were included in the SEER∗Stat Database from 2004 to 2016. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to filter potential prognostic clinical variables. Multivariate analysis from the Cox proportional hazards model was performed to determine the independent prognostic factors on overall survival (OS) and disease-specific survival (DSS), applied to develop nomograms. The Schönfeld residual test verified the proportional hazard assumption. The discrimination and consistency of nomograms was assessed and validated according to concordance index (C-index), receiver operating characteristic (ROC) curves, and calibration curves using an internal 1,000 times bootstrap resampling. The nomogram's net clinical benefit was assessed through decision curve analysis (DCA). Results: A total of 658 patients with SACC were included. Age, T stage, N stage, M stage, histologic grade, and surgery were independent prognostic factors for OS and DSS. Based on these independent prognostic factors, nomograms were developed to predict 3-, 5-, and 10-year OS and DSS. In the validation of 1,000 times bootstrap resampling, the C-index and ROC curves had good discriminatory ability. The calibration curves indicated excellent consistency between the predicted and actual survival results in the nomograms. The DCA curves demonstrated that the nomograms had good clinical benefit and were superior to the TNM stage and other variables. Conclusions: Two nomograms developed in this study precisely predicted the 3-, 5-, and 10-year OS and DSS rates of patients with SACC in accordance with independent prognostic factors, and their clinical value is better than TNM staging, providing a prognostic reference for other SACC patients.

High-Frequency Ultrasound and Shear Wave Elastography in Quantitative Differential Diagnosis of High-Risk and Low-Risk Basal Cell Carcinomas.

OBJECTIVES: The purpose of this study was to investigate the value of high-frequency ultrasound and shear wave elastography (SWE) in quantitative differential diagnosis of high-risk and low-risk basal cell carcinomas (BCCs). METHODS: A total of 52 BCCs confirmed by surgical pathology were studied. Taking pathologic subtypes as reference, all the cases were classified as high-risk BCCs or low-risk BCCs. High-frequency ultrasound parameters and SWE parameters recorded preoperatively were retrospectively analyzed. The differences of two groups were compared. RESULTS: There were 12 high-risk BCCs and 40 low-risk BCCs. The maximum infiltration depth (MID) and average Young's modulus (Eave ) of high-risk BCCs were 5.76 ± 2.56 mm and 31.61 ± 12.36 kPa, whereas of low-risk BCCs were 4.29 ± 1.77 mm and 20.04 ± 4.74 kPa, respectively, P < .05. The area under the receiver operator characteristic curve of MID and Eave were 0.714 and 0.811, P > .05. Taking 5.5 mm of MID and 24.45 kPa of Eave as the threshold for the diagnosis of high-risk BCCs, the sensitivity, specificity, and accuracy were 58.3%, 82.5%, 76.9% and 75.0%, 82.5%, 80.8%, P > .05. CONCLUSIONS: The MID and Eave of the lesion can be used to determine the recurrence risk of BCCs and provide a reference for the development of individualized treatment plans.

Long Non-Coding KCNQ1OT1 Promotes Oxygen-Glucose-Deprivation/Reoxygenation-Induced Neurons Injury Through Regulating MIR-153-3p/FOXO3 Axis.

BACKGROUND: Long non-coding RNAs (LncRNAs) have been reported to play important roles in the pathogenesis and development of many diseases, including cerebral ischemia and reperfusion (I/R) injury. In this study, we aimed to investigate the role of LncRNA-Potassium Voltage-Gated Channel Subfamily Q Member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) in cerebral I/R induced neuronal injury, and its underlying mechanisms. METHODS: Primary mouse cerebral cortical neurons treated with oxygen-glucose deprivation and reoxygenation (OGD/R) in vitro and mice subjected to middle cerebral artery occlusion (MCAO) and reperfusion were used to mimic cerebral I/R injury. Small inference RNA (siRNA) was used to knockdown KCNQ1OT1 or microRNA-153-3p (miR-153-3p). Dual-luciferase assay was performed to detect the interaction between KCNQ1OT1 and miR-153-3p and interaction between miR-153-3p and Fork head box O3a (Foxo3). Flow cytometry analysis was performed to detect neuronal apoptosis. qRT-PCR and Western blotting were performed to detect RNA and protein expressions. RESULTS: KCNQ1OT1 and Foxo3 expressions were significantly increased in neurons subjected to I/R injury in vitro and in vivo, and miR-153-3p expression were significantly decreased. Knockdown of KCNQ1OT1 or overexpression of miR-153-3p weakened OGD/R-induced neuronal injury and regulated Foxo3 expressions. Dual-luciferase analysis showed that KCNQ1OT1 directly interacted with miR-153-3p and Foxo3 is a direct target of miR-153-3p. CONCLUSIONS: Our results indicate that LncRNA-KCNQ1OT1 promotes OGD/R-induced neuronal injury at least partially through acting as a competing endogenous RNA (ceRNA) for miR-153-3p to regulate Foxo3a expression, suggesting LncRNA-KCNQ1OT1 as a potential therapeutic target for cerebral I/R injury.

Endothelial progenitor cells from human fetal aorta cure diabetic foot in a rat model.

OBJECTIVE: Recent evidence has suggested that circulating endothelial progenitor cells (EPCs) can repair the arterial endothelium during vascular injury. However, a reliable source of human EPCs is needed for therapeutic applications. In this study, we isolated human fetal aorta (HFA)-derived EPCs and analyzed the capacity of EPCs to differentiate into endothelial cells. In addition, because microvascular dysfunction is considered to be the major cause of diabetic foot (DF), we investigated whether transplantation of HFA-derived EPCs could treat DF in a rat model. METHODS: EPCs were isolated from clinically aborted fetal aorta. RT-PCR, fluorescence-activated cell sorting, immunofluorescence, and an enzyme-linked immunosorbent assay were used to examine the expressions of CD133, CD34, CD31, Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), von Willebrand Factor (vWF), and Endothelial Leukocyte Adhesion Molecule-1 (ELAM-1). Morphology and Dil-uptake were used to assess function of the EPCs. We then established a DF model by injecting microcarriers into the hind-limb arteries of Goto-Kakizaki rats and then transplanting the cultured EPCs into the ischemic hind limbs. Thermal infrared imaging, oxygen saturation apparatus, and laser Doppler perfusion imaging were used to monitor the progression of the disease. Immunohistochemistry was performed to examine the microvascular tissue formed by HFA-derived EPCs. RESULTS: We found that CD133, CD34, and VEGFR2 were expressed by HFA-derived EPCs. After VEGF induction, CD133 expression was significantly decreased, but expression levels of vWF and ELAM-1 were markedly increased. Furthermore, tube formation and Dil-uptake were improved after VEGF induction. These observations suggest that EPCs could differentiate into endothelial cells. In the DF model, temperature, blood flow, and oxygen saturation were reduced but recovered to a nearly normal level following injection of the EPCs in the hind limb. Ischemic symptoms also improved. Injected EPCs were preferentially and durably engrafted into the blood vessels. In addition, anti-human CD31+-AMA+-vWF+ microvasculars were detected after transplantation of EPCs. CONCLUSION: Early fetal aorta-derived EPCs possess strong self-renewal ability and can differentiate into endothelial cells. We demonstrated for the first time that transplanting HFA-derived EPCs could ameliorate DF prognosis in a rat model. These findings suggest that the transplantation of HFA-derived EPCs could serve as an innovative therapeutic strategy for managing DF.

Impact of BMI on gonadorelin-stimulated LH peak in premenarcheal girls with idiopathic central precocious puberty.

OBJECTIVE: To clarify the impact of body mass index (BMI) on luteinizing hormone (LH) secretion in response to gonadorelin (GnRH) stimulation testing in girls diagnosed with idiopathic central precocious puberty (ICPP). METHODS: Retrospective single-center cohort study was carried out in 865 confirmed ICPP girls who underwent GnRH stimulation tests. Pubertal development according to Tanner, sex hormone parameters, and LH secretion in response to GnRH-stimulation was compared. RESULTS: Around 609 girls were of normal weight (70.4%), while 168 children (19.4%) were overweight, and 88 (10.2%) were obese. Peak LH levels after GnRH were much higher in the normal-weight group, with a median of 9.1 mIU ml(-1) (interquartile 5.2-13.1), compared with the median peak LH in the overweight and obese groups (8.5 mIU ml(-1), interquartile 5.3-11.6, and 6.2 mIU ml(-1), interquartile 5.3-11.0, respectively P < 0.001 for all comparisons). Peak LH/FSH ratio was also lower in the obese group (median 0.6, interquartile 0.68-0.90) compared with the normal-weight (median 0.8, interquartile 0.61-1.11) and overweight (median 0.8, interquartile 0.64-0.92) groups. CONCLUSIONS: Higher BMI is associated with lower LH response to GnRH-stimulation testing in girls with ICPP. It is recommended that BMI should be considered when interpreting GnRH-stimulation tests.

[Treatment of advanced Wilms' tumor].

OBJECTIVE: To improve prognosis of the patients with advanced Wilms' tumor, the authors compared different therapeutic strategies including preoperative transcatheter arterial chemoembolization (TACE), conventional preoperative chemotherapy and initial surgery. METHODS: Sixty-two patients aged from 5 months to 10 years (mean 3.2 years) were identified from medical records to have histologically confirmed advanced Wilms' tumor during the period from January 1993 to December 2002. The criteria for choice were huge tumor size with a volume more than 550 ml or the mass extending beyond the midline, involvement of vital structures, inferior vena cava invasion, distal metastasis or bilateral Wilms' tumor judged by imaging examination. All cases were divided into 3 groups according to the treatment received: 31 cases in group TACE received preoperative transcatheter arterial chemoembolization with Lipiodol-Epirubicin (EPI)-Vincristine emulsion. One week after TACE, systemic chemotherapy with Actinomycin D (ACTD) was administered and tumor resected at two weeks after TACE. 20 cases in group PC received conventional preoperative chemotherapy with VCR, ACTD plus EPI for 4-5 weeks, and 11 cases in group IS underwent initial surgery. Postoperative treatment for all patients was based on the postoperative staging and tumor histology. RESULTS: In the patients treated with TACE, no drug-induced complications such as cardiotoxicity, nephrotoxicity, hepatic dysfunction or bone marrow suppression were observed except for mild fever due to tumor necrosis. The percentages of tumor size shrinkage were 32.4% and 20.3% in group TACE and group PC, respectively (P < 0.05). Complete surgical removal of the tumor was achieved in 27 patients (87.1%) in group TACE, significantly higher in comparison with 14 in group PC (70.0%, P < 0.05) and 2 in group IS (18.2%, P < 0.01). Event-free survival (EFS) at 2 years was 87.1% (27/ 31), 60.0% (12/20) and 18.2% (2/11), respectivrely. EFS at 4 years was 84.6% (11/13), 56.3% (9/16 ) and 18.2% (2/11) in groups TACE, PC and IS, respectively. CONCLUSION: The present study has shown that both preoperative TACE and conventional preoperative chemotherapy can be applied to the patients with advanced Wilms' tumor who are not candidates for immediately surgical resection. The survival is significantly increased in the patients undergoing preoperativeTACE when compared with conventional preoperative chemotherapy and initial surgery.