Delta Radiomics Based on Longitudinal Dual-modal Ultrasound Can Early Predict Response to Neoadjuvant Chemotherapy in Breast Cancer Patients.

RATIONALE AND OBJECTIVES: To develop a monitoring model using radiomics analysis based on longitudinal B-mode ultrasound (BUS) and shear wave elastography (SWE) to early predict pathological response to neoadjuvant chemotherapy (NAC) in breast cancer patients. MATERIALS AND METHODS: In this prospective study, 112 breast cancer patients who received NAC between September 2016 and March 2022 were included. The BUS and SWE data of breast cancer were obtained prior to treatment as well as after two and four cycles of NAC. Radiomics features were extracted followed by measuring the changes in radiomics features compared to baseline after the second and fourth cycles of NAC (△R [C2], △R [C4]), respectively. The delta radiomics signatures were established using a support vector machine classifier. RESULTS: The area under receiver operating characteristic curve (AUC) values of △RBUS (C2) and △RBUS (C4) for predicting the response to NAC were 0.83 and 0.84, while those of △RSWE (C2) and △RSWE (C4) were 0.88 and 0.90, respectively. △RSWE exhibited significantly superior performance to △RBUS for predicting NAC response (Delong test, p < 0.01). No significant differences were observed in the performances between △R (C2) and △R (C4) based on BUS or SWE data. The longitudinal dual-modal ultrasound radiomics (LDUR) model had an excellent discrimination, good calibration and clinical usefulness, with the AUC, sensitivity and specificity of 0.97, 95.52% and 91.11%, respectively. CONCLUSION: The LDUR model achieved excellent performance in predicting the pathological response to chemotherapy during the early stages of NAC for breast cancer.

Deep Learning Model Based on Dual-Modal Ultrasound and Molecular Data for Predicting Response to Neoadjuvant Chemotherapy in Breast Cancer.

RATIONALE AND OBJECTIVES: To carry out radiomics analysis/deep convolutional neural network (CNN) based on B-mode ultrasound (BUS) and shear wave elastography (SWE) to predict response to neoadjuvant chemotherapy (NAC) in breast cancer patients. MATERIALS AND METHODS: In this prospective study, 255 breast cancer patients who received NAC between September 2016 and December 2021 were included. Radiomics models were designed using a support vector machine classifier based on US images obtained before treatment, including BUS and SWE. And CNN models also were developed using ResNet architecture. The final predictive model was developed by combining the dual-modal US and independently associated clinicopathologic characteristics. The predictive performances of the models were assessed with five-fold cross-validation. RESULTS: Pretreatment SWE performed better than BUS in predicting the response to NAC for breast cancer for both the CNN and radiomics models (P < 0.001). The predictive results of the CNN models were significantly better than the radiomics models, with AUCs of 0.72 versus 0.69 for BUS and 0.80 versus 0.77 for SWE, respectively (P = 0.003). The CNN model based on the dual-modal US and molecular data exhibited outstanding performance in predicting NAC response, with an accuracy of 83.60% ± 2.63%, a sensitivity of 87.76% ± 6.44%, and a specificity of 77.45% ± 4.38%. CONCLUSION: The pretreatment CNN model based on the dual-modal US and molecular data achieved excellent performance for predicting the response to chemotherapy in breast cancer. Therefore, this model has the potential to serve as a non-invasive objective biomarker to predict NAC response and aid clinicians with individual treatments.

Combining conventional ultrasound and sonoelastography to predict axillary status after neoadjuvant chemotherapy for breast cancer.

OBJECTIVE: To determine the ability of conventional ultrasound (US) combined with shear wave elastography (SWE) to reveal axillary status after neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: From September 2016 to December 2021, 201 patients with node-positive breast cancer who underwent NAC were enrolled in this prospective study. Conventional US features of axillary lymph nodes and SWE characteristics of breast lesions after NAC were analyzed. The diagnostic performances of US, SWE, and their combination were assessed using multivariate logistic regression and receiver operator characteristic curve (ROC) analyses. RESULTS: The area under the ROC curve (AUC) for the ability of conventional US features to determine axillary status after NAC was 0.82, with a sensitivity of 85.23%, a specificity of 67.39%, and an accuracy of 76.11%. Shear wave velocity (SWV) displayed moderate performance for predicting axilla status after NAC with SWVmean demonstrating an AUC of 0.85. Cortical thickness and shape of axillary nodes and SWVmean of breast tumors were independently associated with axillary nodal metastasis after NAC. Compared to conventional US, the combination of conventional US of axillary lymph nodes with SWE of breast lesions achieved a significantly higher AUC (0.90 vs 0.82, p < 0.01, Delong's test) with a sensitivity of 87.50%, improved specificity of 82.61% and accuracy of 85.00%. CONCLUSIONS: Breast SWE was independently associated with residual metastasis of axillary node after NAC in patients with initially diagnosed positive axilla. Combining SWE with conventional US showed good diagnostic performance for axillary node disease after NAC. KEY POINTS: • Breast SWE can serve as a supplement to axilla US for the evaluation of the axilla after NAC. • The combination of axilla US with breast SWE may be a promising method to facilitate less-invasive treatment in patients receiving NAC.

[Preliminary study of the relationship between tumor like Sjögren's syndrome and malignant lymphoma].

OBJECTIVE: To investigate the clinical and laboratory characteristics of tumor like Sjögren's syndrome (TLSS) patients and non-tumor like Sjögren's syndrome (NTLSS) and the incidence of lymphoma in patients of Sjögren's syndrome (SS). METHODS: A retrospective analysis was carried out in 199 primary SS (including TLSS) patients who were recruited in Peking University School and Hospital of Stomatology from 1998 to 2010. Clinical and laboratory information were collected. The patients were divided into two groups: TLSS (n = 25) and NTLSS (n = 174). Clinical and laboratory characteristics were compared between these two groups by a statistical analysis. RESULTS: Of the 25 TLSS patients, 23 had enlargements of parotid glands and 2 had enlargements of submandibular glands. There were significant differences of salivary scintigraphy appearance (P = 0.018), hypergammaglobulinemia (P = 0.014), rheumatoid factor positive rate (P = 0.001), formation of the ectopic germinal centers (P = 0.014), double positive rate of anti-SSA antibody and anti-SSB antibody (P < 0.001) between the TLSS and NTLSS patients. Among the 25 TLSS patients, 3 developed lymphomas, accounting for 1.5% (3/199) of the total 199 patients and 12% (3/25) of the TLSS patients. Lymphoma subtypes included one diffused large B-cell lymphoma and two mucosa-associated lymphoid tissue lymphoma. There was no lymphoma detected in NTLSS patients. CONCLUSIONS: There are clinical and laboratory differences between TLSS and NTLSS patients, with a more tendency to develop lymphomas in TLSS patients.

Molecular behavior of water in TiO2 nano-slits with varying coverages of carbon: a molecular dynamics simulation study.

It is well known that titanium dioxide (TiO(2)) is biocompatible and environmentally friendly. Consequently, TiO(2) is widely applied in many fields, such as implant materials, photocatalysis, pigments, cosmetic additives, etc. Mesoporous TiO(2) finds many industrial applications, because of its high surface area and stable structure. However, the strong interaction between TiO(2) and water molecules sometimes limits its application to solution environments. Our previous computational work showed that changes to the surface chemistry of TiO(2) can affect the hydrogen bond network of water molecules on the TiO(2) surface, and so influence the diffusion of water in the slits. Thus, a carbon-modified TiO(2) surface could be an alternative way to avoid this limitation. In this work, a slit pore model with a modified TiO(2) surface (pore widths 1.2 nm, 1.6 nm and 2.0 nm) with varying carbon coverages (0%, 7%, 47%, 53%, 93% and 100%) was presented. Molecular dynamics (MD) simulations were then performed to investigate the sorption and diffusion of water in these slits. Simulation results showed that the interfacial water molecules on bare TiO(2) regions were little affected by the neighboring carbon, and they have the same properties as those on bare TiO(2) surfaces. However, the diffusion of water molecules in the center of the slit was enhanced on increase of carbon coverage, because the carbon layer broke the hydrogen bond network between the interfacial water molecules and those on the bare TiO(2) surface. It was found that in the slits (>1.2 nm) fully covered by carbon the diffusion coefficients of water are larger than that of bulk water. Moreover, large pore sizes caused an increase in the mobility of water molecules in carbon-modified TiO(2), in agreement with previous experimental work.

beta-catenin expression pattern in primary oral squamous cell carcinoma.

BACKGROUND: Beta-catenin, a 92 kDa protein that binds to the cytoplasmic tail of E-cadherin, has an essential role in intercellular adhesion and signal transduction. Aberrant expression of beta-catenin has been associated with progression and metastasis of various human cancers. The aim of this study was to elucidate the expression pattern of beta-catenin in primary oral squamous cell carcinoma and examine the correlation between beta-catenin expression and tumor differentiation, histological grade and lymph node status as well as its clinical significances. METHODS: Seventy-six patients with oral squamous cell carcinoma and sixteen metastatic lymph nodes were studied. The beta-catenin expression was determined by immunohistochemical staining. The correlation with clinical, histological data was analyzed statistically. RESULTS: Normal oral epithelium showed strong beta-catenin expression at the cell membrane, but no cytoplasmic or nuclear expression. Different degrees of reduced expression of beta-catenin at the cell membrane were found in 54 cases with squamous cell carcinoma (71%). Cytoplasmic beta-catenin expression was found in 17 tumors (22.4%). Three cases were found with nuclear beta-catenin expression. In sixteen lymph nodes with metastatic squamous cell carcinoma, negative beta-catenin expression at the cell membrane was seen in 13 tumors (81.2%) and weak expression in 3 tumors (18.8%). Statistical analysis showed that there was an inverse correlation between beta-catenin expression and lymph node status and histological grade of tumors. CONCLUSIONS: Reduced beta-catenin expression at the cell membrane is clearly associated with lymph node metastasis. A reduced expression of beta-catenin may constitute a hallmark of aggressive biological behavior of squamous cell carcinoma.

[Osteoclastic bone destruction and its regulating factors in oral squamous cell carcinoma].

OBJECTIVE: To investigate the osteoclastic activity in oral squamous cell carcinoma (OSCC) invading the jaws and to observe the expression of RANKL and OPG, the two bone resorption related cytokines, in these cases. METHODS: Twelve cases of OSCC invading the mandible were studied. After pathological diagnosis, operations were done to remove part of the mandible depending upon the X-ray findings. Fresh soft tissue specimens were frozen-sectioned and other specimens with the bone tissue were fixed and decalcified to make paraffin sections. Tartrate-resistant acid phosphatase(TRAP) staining and immunohistochemical staining were then applied to observe the location of osteoclasts and the expression of RANKL and OPG. RESULTS: TRAP positive multinuclear cells were detected near the interface between the bone and tumor. RANKL positive cells were commonly seen on the endothelium of blood vessel and basement membrane of the epithelium. But OPG reactivities were not seen in these sections. CONCLUSION: The bone destruction caused by OSCC is mediated by osteoclasts but not by cancer cell itself. It appears that the differentiation and activation of osteoclasts were induced by OSCC through cytokines like RANKL.

[Expression of receptor activator of NF-kappa B ligand and osteoprotegerin protein in the giant cell lesions of jaw].

OBJECTIVE: To detect the expression of RANKL and OPG protein in the giant cell lesions of jaw and to study the mechanism of this lesion. METHODS: RANKL and OPG were detected by immunohistochemistry (SP) in 24 paraffin-embedded and 2 frozen specimens of central giant cell lesion of jaw. RESULTS: RANKL signals were strongly positive in the vascular epithelial cells. They also could be found in fibrous stroma, bone matrix, and stromal spindle cells, even in some cytomembrane of multinucleated giant cells. OPG was detected in multinucleated giant cells and a fraction of round mononuclear cells. CONCLUSIONS: Active vascular epithelial cells are contributed to the formation of multinucleated giant cells through regulating RANKL, and RANKL could play its role by paracrine and autocrine, which might be inhibited by OPG.

[Expressions of PDCD5 and p53 in oral leukoplakia and oral squamous cell carcinoma].

OBJECTIVE: To study the relationship of the expressions of new apoptosis-related gene PDCD5 and p53 in oral normal mucosa, oral leukoplakia and oral squamous cell carcinoma. METHODS: The expressions of PDCD5 and p53 were observed separately in 17 samples of oral normal mucosa, 60 of oral leukoplakia, and 30 of oral squamous cell carcinoma by Immunohistochemical means. RESULTS: PDCD5 positive rate in oral normal mucosa was 88.2%, in oral leukoplakia was 63.3%, and in oral squamous cell carcinoma was 30%. P53 positive rate in oral normal mucosa was 0, in oral leukoplakia was 31.7%, and in oral squamous cell carcinoma was 60%. There was a negative relationship between PDCD5 SII and P53 SII in every lesion. CONCLUSION: It suggests that both PDCD5 and p53 could be used as molecular markers of carcinogenesis for oral epithelium.

[Enamelin transcriptional expression in developing postnatal rat tooth germ].

OBJECTIVE: To observe the transcriptional expression of enamelin in developing postnatal rat first mandibular molar germs, for further studies of functions of enamelin in enamel development and mineralization. METHODS: Tissue slices of first mandibular molar germ of rat 1, 3, 7, 10, 14 days after birth were prepared. The enamelin mRNA expression was identified by in situ hybridization. RESULTS: Enamelin mRNA was observed in both ameloblast and odontoblast in 1-10 day old rat postnatal first mandibular molar germs. Enamelin mRNA appeared very weakly at 1st day, and increased through 3rd day, reached the maximum at 7th day, and reduced at 10th day and became negative at 14th day postnatally; while the expression of enamelin mRNA in odontoblast maintained lower from 1st to 10th day and negative at 14th day postnatally. CONCLUSION: Enamelin gene transcriptional expression lasts from preameloblast to maturation ameloblast, which suggests that enamelin may participate in the development of enamel and mantle dentin.