Multiparametric US for Identifying Metabolic Dysfunction-associated Steatohepatitis: A Prospective Multicenter Study.

Background Noninvasive evaluation of metabolic dysfunction-associated fatty liver disease (MAFLD) with multiparametric US is essential, but multicenter studies are lacking. Purpose To evaluate the ability of multiparametric US with attenuation imaging (ATI) and two-dimensional (2D) shear-wave elastography (SWE) for predicting metabolic dysfunction-associated steatohepatitis (MASH) in participants with MAFLD, regardless of hepatitis B virus infection status. Materials and Methods This prospective cross-sectional multicenter study of consecutive adults with MAFLD who underwent multiparametric US with ATI and 2D SWE, as well as liver biopsy, from September 2020 to June 2022 was conducted in 12 tertiary hospitals in China. Multivariable logistic regression was performed to assess risk factors associated with MASH. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate diagnostic performance in predicting MASH in training and validation groups (6:4 ratio of participants), and for a post hoc subgroup analysis of hepatitis B virus infection and diabetes. Results A total of 424 participants (median age, 47 years; IQR, 34-59 years; 244 male) were evaluated, including 332 participants (78%) with MASH and 92 (22%) without. Attenuation coefficient (AC) (odds ratio [OR], 3.32 [95% CI: 1.94, 5.71]; P < .001), alanine aminotransferase (ALT) level (OR, 4.42 [95% CI: 1.78, 10.94]; P = .001), and international normalized ratio (INR) (OR, 0.59 [95% CI: 0.37, 0.95]; P = .03) were independently associated with MASH. A combined model (AC, ALT, and INR) had AUCs of 0.85 (95% CI: 0.79, 0.91) and 0.77 (95% CI: 0.69, 0.85) for predicting MASH in the training and validation groups, respectively. AUC values for the subgroups with and without diabetes were 0.83 (95% CI: 0.72, 0.94) and 0.81 (95% CI: 0.75, 0.87) and for the subgroups with and without hepatitis B were 0.82 (95% CI: 0.74, 0.90) and 0.79 (95% CI: 0.71, 0.87), respectively. Conclusion A model combining AC, ALT level, and INR showed good discrimination ability for predicting MASH in participants with MAFLD. Clinical trial registration no. NCT04551716 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Reuter in this issue.

Analysis of differentially expressed proteins in lymph fluids related to lymphatic metastasis in a breast cancer rabbit model guided by contrast­enhanced ultrasound.

The aim of the present study was to identify differentially expressed proteins in the lymph fluid of rabbits with breast cancer lymphatic metastasis compared with healthy rabbits and to analyze and verify these proteins using proteomics technologies. In the process of breast cancer metastasis, the composition of the lymph fluid will also change. Rabbits with breast cancer lymph node metastasis and normal rabbits were selected for analysis. Lymph fluid was extracted under the guidance of percutaneous contrast-enhanced ultrasound. Label-free quantitative proteomics was used to detect and compare differences between the rabbit cancer model and healthy rabbits and differential protein expression results were obtained. Bioinformatics analysis was performed using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis software, selecting the most significantly differentially expressed proteins. Finally, parallel reaction monitoring technology was applied for validation. A total of 547 significantly differentially expressed proteins were found in the present study, which included 371 upregulated proteins and 176 downregulated proteins. The aforementioned genes were mainly involved in various cellular and metabolic pathways, including upregulated proteins, such as biliverdin reductase A and isocitrate dehydrogenase 2 and downregulated proteins, such as pyridoxal kinase. The upregulated proteins protein disulfide-isomerase 3, protein kinase cAMP-dependent type I regulatory subunit α and ATP-binding cassette sub-family C member 4 participated in immune regulation, endocrine regulation and anti-tumor drug resistance regulation, respectively. Compared with healthy rabbits, rabbits with breast cancer metastasis differentially expressed of a number of different proteins in their lymph, which participate in the pathophysiological process of tumor occurrence and metastasis. Through further research, these differential proteins can be used as predictive indicators of breast cancer metastasis and new therapeutic targets.

The potential role of combined shear wave elastography and superb microvascular imaging for early prediction the pathological response to neoadjuvant chemotherapy in breast cancer.

Objectives: The potential role of shear wave elastography (SWE) and superb microvascular imaging (SMI) for early assessment of treatment response to neoadjuvant chemotherapy (NAC) in breast cancer remains unexplored. This study aimed to identify potential factors associated with the pathological response to NAC using these advanced ultrasound techniques. Methods: Between August 2021 and October 2022, 68 patients with breast cancer undergoing NAC were recruited. Patients underwent conventional ultrasonography, SMI, and SWE examinations at baseline and post-2nd cycle of NAC. Maximum tumor diameter (Dmax), maximum elastic value (Emax), peak systolic velocity (PSV), and resistance index (RI) at baseline and the rate of change of these parameters post-2nd cycle were recorded. After chemotherapy, all patients underwent surgery. Using the Miller-Payne's grade, patients were categorized into response (grades 3, 4, or 5) and non-response (grades 1 or 2) group. Parameters were compared using t-tests at baseline and post-2nd cycle. Binary logistic regression analysis was used to identify variables and their odds ratios (ORs) related to responses and a prediction model was established. ROC curves were drawn to analyze the efficacy of each parameter and their combined model for early NAC response prediction. Results: Among the 68 patients, 15(22.06%) were categorized into the non-response group, whereas 53(77.94%) were categorized into the response group. At baseline, no significant differences were observed between the two groups (p>0.05). Post-2nd cycle of NAC, rates of change of Emax, PSV and RI (ΔEmax, ΔPSV and ΔRI) were higher in responders than non-responders (p<0.05). Binary logistic regression analysis revealed that ΔEmax (OR 0.797 95% CI, 0.683-0.929), ΔPSV (OR 0.926, 95%CI, 0.860-0.998), and ΔRI (OR 0.841, 95%CI, 0.736-0.960) were independently associated with the pathological response of breast cancer after NAC. The combined prediction model exhibited higher accuracy in the early evaluation of the response to NAC (AUC 0.945, 95%CI, 0.873-1.000). Conclusion: SWE and SMI techniques enable early identification of tumor characteristics associated with the pathological response to NAC and may be potentially indicative of an effective response. These factors may eventually be used for the early assessment of NAC treatment for clinical management.

PAIP2 is a potential diagnostic and prognostic biomarker of breast cancer and is associated with immune infiltration.

Breast cancer is the second highest incidence of cancer in the world. It is of great significance to find biomarkers to diagnose breast cancer and predict the prognosis of breast cancer patients. PAIP2 is a poly (A) -binding protein interacting protein that regulates the expression of VEGF. However, the possible role of PAIP2 in the progression of breast cancer is still unknown. RT-qRCR and Western blotting were used to verify the expression of PAIP2 in breast cancer cells and normal breast cells. The data of breast cancer samples were obtained in the TCGA database and the HPA database to analyze the expression of PAIP2 in breast cancer samples. Transwell experiment and CCK8 experiment confirmed the changes in the invasion and proliferation ability of PAIP2 after siRNA was down-regulated. Using bioinformatics technology to explore the prognostic value of PAIP2 and its possible biological function, and its effect on tumor immunity and immunotherapy. Studies have shown that PAIP2 has higher expression in breast cancer tissues and breast cancer cells. PAIP2 can promote the proliferation and invasion of breast cancer cells and has significantly high expression in higher tumor stages. The high expression of PAIP2 is associated with better OS in breast cancer patients and is negatively correlated with most chemotherapeutic drug sensitivity and IPS in cancer immunotherapy. Our study explored the potential value of PAIP2 as a biomarker for diagnosis and prognosis and may predict the efficacy of immunotherapy, providing reference for the follow-up study on the role of PAIP2 in breast cancer.

Differential Diagnosis Value of Shear-Wave Elastography for Superficial Enlarged Lymph Nodes.

Objectives: To evaluate the diagnostic efficiency and diagnostic threshold of conventional US and shear-wave elastography (SWE) in superficial enlarged lymph nodes (LNs). Methods: A total of 204 patients with superficial enlarged LNs were enrolled in this retrospective study aged 46.0 ± 15.2 years from March 2020 to March 2021. LNs with a long axis larger than 0.7 cm were considered as superficial enlarged. Before the histological biopsy, LNs that were considered suspicious according to both conventional US and SWE were included, while LNs with no or unclear pathological results, or with no satisfactory SWE images, were excluded. The conventional and 2-D SWE examinations were performed with Aplio i800 and Acuson sequoia equipped with i18LX5 linear-array transducer (5-18 MHz) and 10L4 linear-array transducer (4-10 MHz), respectively. Both E Median and Vs Median parameters were investigated by two senior ultrasound physicians. The pathological results were performed as the gold standard. Results: Variables including transverse axis size, lymphatic hilum, L/T ratio, echogenicity, and color Doppler pattern were considered significant. The mean E Median value in benign, metastatic LNs, and lymphoma were 28.26 ± 8.87 kPa, 77.46 ± 22.85 kPa, and 50.37 ± 5.41 kPa (p <0.001), while Vs Median values were 3.02 ± 0.50 m/s, 4.87 ± 0.90 m/s, and 4.09 ± 0.22 m/s, respectively (p < 0.001). The diagnostic performance indicated the high sensitivity, specificity, PPV, NPV, and overall accuracy of conventional US combined with SWE. The optimal cutoff values of E Median and Vs Median for predicting malignant LNs were 42.90 kPa and 3.73 m/s, respectively. As AUC value, sensitivity, specificity, accuracy, PPV, and NPV revealed, the indexes of E Median were 0.976, 0.927, 0.975, 0.946, 0.983, and 0.897, respectively, while Vs Median were 0.970, 0.927, 0.963, 0.941, 0.975, and 0.895, respectively (p <0.001). The ROC curves of both E Median (AUC=0.976) Vs Median (AUC=0.970) suggested the remarkable diagnostic efficiency in distinguishing benignity between suspected malignant LNs. Conclusions: Above results indicated that conventional US together with 2-D SWE could elevate the diagnostic performance. Meanwhile, the parameters of 2-D SWE including E Median and Vs Median could effectively assess malignant LNs, which provide valuable differentiating information in superficial enlarged LNs.

Low-Intensity Focused Ultrasound-Augmented Multifunctional Nanoparticles for Integrating Ultrasound Imaging and Synergistic Therapy of Metastatic Breast Cancer.

The metastasis of breast cancer is believed to have a negative effect on its prognosis. Benefiting from the remarkable deep-penetrating and noninvasive characteristics, sonodynamic therapy (SDT) demonstrates a whole series of potential leading to cancer treatment. To relieve the limitation of monotherapy, a multifunctional nanoplatform has been explored to realize the synergistic treatment efficiency. Herein, we establish a novel multifunctional nano-system which encapsulates chlorin e6 (Ce6, for SDT), perfluoropentane (PFP, for ultrasound imaging), and docetaxel (DTX, for chemotherapy) in a well-designed PLGA core-shell structure. The synergistic Ce6/PFP/DTX/PLGA nanoparticles (CPDP NPs) featured with excellent biocompatibility and stability primarily enable its further application. Upon low-intensity focused ultrasound (LIFU) irradiation, the enhanced ultrasound imaging could be revealed both in vitro and in vivo. More importantly, combined with LIFU, the nanoparticles exhibit intriguing antitumor capability through Ce6-induced cytotoxic reactive oxygen species as well as DTX releasing to generate a concerted therapeutic efficiency. Furthermore, this treating strategy actives a strong anti-metastasis capability by which lung metastatic nodules have been significantly reduced. The results indicate that the SDT-oriented nanoplatform combined with chemotherapy could be provided as a promising approach in elevating effective synergistic therapy and suppressing lung metastasis of breast cancer.

2020 Chinese guidelines for ultrasound malignancy risk stratification of thyroid nodules: the C-TIRADS.

Thyroid nodules are very common all over the world, and China is no exception. Ultrasound plays an important role in determining the risk stratification of thyroid nodules, which is critical for clinical management of thyroid nodules. For the past few years, many versions of TIRADS (Thyroid Imaging Reporting and Data System) have been put forward by several institutions with the aim to identify whether nodules require fine-needle biopsy or ultrasound follow-up. However, no version of TIRADS has been widely adopted worldwide till date. In China, as many as ten versions of TIRADS have been used in different hospitals nationwide, causing a lot of confusion. With the support of the Superficial Organ and Vascular Ultrasound Group of the Society of Ultrasound in Medicine of the Chinese Medical Association, the Chinese-TIRADS that is in line with China's national conditions and medical status was established based on literature review, expert consensus, and multicenter data provided by the Chinese Artificial Intelligence Alliance for Thyroid and Breast Ultrasound.

Evaluation of Adenoid Hypertrophy with Ultrasonography.

OBJECTIVES: To determine the reliability of ultrasound in the diagnosis of adenoid hypertrophy in children. METHODS: The subjects were divided into three groups: Group A: Pre-experiment group: 30 children who were hospitalized for adenoidal hypertrophy were selected, and preoperative ultrasound was used to measure adenoid thickness. Their re-confirmed Adenoid ultrasound measurement thickness was obtained during surgery under the guidance of metal instruments; Group B: Ultrasound screening group: 1898 children aged 3-12 y were selected, and their adenoids were examined by ultrasonography to observe the size, shape, echo and blood flow of adenoids and the thickness of adenoids; Group C: Surgical resection group: 133 hospitalized patients were selected, and their adenoid ultrasound measurement thickness (AUT), the adenoid-nasopharynx (A/N) ratio was calculated based on nasopharyngeal lateral radiographs and obstruction ratio was obtained in electronic nasopharyngoscopy [extent of adenoid-posterior nostril occlusion (EANC)] were compared. RESULTS: In Group A, there was no statistical difference in the measurements of the adenoids between the preoperative ultrasound and the ultrasound measurements under the guidance of intraoperative metal instruments (P > 0.05). In Group B, the adenoids of 1898 children aged 3-12 y were measured and were found thickest at 6 y, with an average of 5.035 ± 0.0609 mm. There was no statistical difference in adenoid thickness between boys and girls (P > 0.05). In Group C, there was a linear correlation between AUT and A/N ratio (r = 0.999, P = 0.01) and between AUT and EANC (r = 0.950, P = 0.000). CONCLUSIONS: In children between 3 and 12 y of age, AUT greater than 6 mm may be considered for surgical resection of adenoid hypertrophy.

[Establishment of lymph node metastasis of MDA-MB-231 breast cancer model in nude mice].

OBJECTIVE: To establish lymph node metastasis of breast cancer model in nude mices using MDA-MB-231 cell lines or tumor masses. METHODS: Divided twelve female nude mices of five weeks into A, B groups randomly. A group had seven nude mices, B group had five nude mices. A group nude mices were injected with MDA-MB-231 cells suspension into the second right mammary fat pad. Two weeks after emerged tumors, the orthotopic tumors of two nude mices of A group were dissected and then implanted into the second right mammary fat pad of B group nude mices. The other mices of A group continued to be fed. After six weeks of inoculation, we excised the tumors and the swollen lymph nodes in right axilla of all nude mices to make pathological examination. RESULTS: ① A group have a 7/7 tumor formation rate 7 days after implanted, B group was 5/5 5 days after implanted. ② The tumor volumes between the two groups had evident difference (P = 0.023), and the tumor volume of B group was bigger than A group. ③ A group had three nude mices which had one tumid lymph node respectively, the lymph node enlargement rate was 3/5; B group only had one nude mice that had one tumid lymph node, the lymph node enlargement rate was 1/5, the lymph node enlargement rate between the two groups showed no significant difference (P = 0.524). ④ The result of pathology in the two groups testified the tumors were invasive ductal carcinoma. The swollen lymph nodes in A group were reactive hyperplasia lymph nodes; the swollen lymph nodes in B group was metastatic lymph node. CONCLUSIONS: The method of orthotopic implantation with MDA-MB-231 tumor mass to establish lymph node metastasis of breast cancer model in nude mice, can provide a useful mean to research the lymph node metastasis mechanism of breast cancer.