Radiation-induced liver disease (RILD) poses a major clinical challenge in radiotherapy, transplantation preconditioning, or radiation accidents, yet its pathogenesis is poorly understood due to limited animal models. Here, we establish a translational pig model recapitulating human RILD pathology within 4 weeks post-40 Gy irradiation, featuring veno-occlusive disease (VOD) and centrilobular necrosis. Single-cell atlas analyses identify ferroptosis as a key driver of hepatocyte death during RILD initiation. Ferroptosis inhibition with liproxstatin-1 (Lip-1) not only prevents RILD progression but also reverses histological damage and restores liver function. Mechanistically, Lip-1 treatment restores dysregulated gene expression profiles, particularly associated with hepatocyte ferroptosis, while stimulating hepatic regeneration via coordinated proliferation of hepatocytes and endothelial cells. Our findings establish ferroptosis inhibition as a therapeutic strategy for RILD, demonstrating its dual role in cytoprotection and regeneration. This large animal model provides a robust platform to optimize radiotherapy regimens, improve transplant conditioning, and develop targeted radioprotectants.
OBJECTIVE:To investigate whether sonocavitation, induced by low-intensity focused ultrasound combined with microbubbles, can overcome paclitaxel resistance in ovarian cancer by promoting apoptosis through reactive oxygen species (ROS)-mediated mitochondrial dysfunction. METHODS:Paclitaxel-resistant ovarian cancer tissues and cell lines were compared with chemotherapy-sensitive counterparts for the expression of apoptosis-related proteins. Sonocavitation treatment was applied to resistant cells using optimized ultrasound parameters. Apoptosis, ROS production, mitochondrial morphology, oxygen consumption, mitochondrial membrane potential and mitochondrial membrane proteins were evaluated by flow cytometry, transmission electron microscopy, oxygen consumption assays, adenosine triphosphate (ATP) measurements, mitochondrial membrane potential assay kit staining and Western blotting. In vivo antitumor efficacy and biosafety were examined in paclitaxel-resistant xenograft mouse models, with tumor growth curves, survival analysis, and hematological/organ histology assessments. RESULTS:Paclitaxel-resistant ovarian cancer tissues exhibited elevated Bcl-2 and reduced Bax and Caspase-3, indicating impaired intrinsic apoptosis. Sonocavitation significantly increased apoptosis in resistant ovarian cancer cells and induced marked mitochondrial dysfunction, including reduced mitochondrial size, disrupted oxygen consumption, decreased ATP levels, collapse of mitochondrial membrane potential and destruction of mitochondrial membrane proteins. Cytochrome c release and activation of cleaved Caspase-3 confirmed mitochondrial-dependent apoptosis. In vivo, sonocavitation suppressed tumor growth and prolonged survival without causing systemic toxicity. ROS scavengers partially reversed these effects, confirming that ROS accumulation is a key mediator of the therapeutic mechanism. CONCLUSION:Sonocavitation induces apoptosis in paclitaxel-resistant ovarian cancer through ROS-mediated mitochondrial dysfunction and demonstrates effective tumor-suppressive activity with a favorable safety profile. These findings support sonocavitation as a promising adjuvant strategy to overcome chemoresistance and enhance ovarian cancer treatment outcomes.
Objective:To explore the threshold and efficacy of thyroglobulin assessment in the needle washout after fine needle aspiration (FNA-Tg) in the preoperative diagnosis of cervical lymph metastasis of thyroid papillary carcinoma (PTC).Methods:A retrospective analysis was performed on the FNA-Tg results of a total of 541 lymph nodes in 410 patients who underwent thyroid node surgery at the Department of Head Neck Surgery, Sir Run Run Shaw Hospital of Zhejiang University College of Medicine from July 2016 to January 2018. Taking the postoperative lymph node pathological results as the "gold standard", the ROC curve was plotted to obtain the optimal diagnostic threshold of FNA-Tg for cervical lymph node metastasis and evaluate its diagnostic efficacy. According to the level of serum thyroglobulin (sTg), the lymph nodes were divided into either a low sTg group (sTg ≤10 ng/ml) or a high sTg group (sTg >10 ng/ml), the ROC curve was plotted to analyze the diagnostic threshold of FNA-Tg in the two groups. The diagnostic threshold and efficacy of FNA-Tg/sTg ratio and FNA-Tg-sTg difference were then analyzed.Results:The ROC curve of FNA-Tg for diagnosis of lymph node metastasis was plotted, and the optimal diagnostic threshold of FNA-Tg was determined to be 0.835 ng/ml. Using this threshold as the cut-off point, the sensitivity and specificity were 88.5% and 97.5%, respectively, and the area under the ROC curve (AUC) was 0.944 (95%CI: 0.914~0.974). The level of FNA-Tg was correlated with the level of sTg (r=0.350, P<0.001). Then, the lymph nodes were divided into either a low sTg group (n = 296) or a high sTg group (n = 245) according to the level of sTg, and the optimal diagnostic threshold for the two groups was determined to be 0.825 ng/ml (AUC = 0.909, 95%CI: 0.838~0.981) and 0.875 ng/ml (AUC = 0.951, 95%CI: 0.918~0.984), respectively. The optimal diagnostic cut-off of FNA-Tg/sTg ratio was determined to be 0.145; using this cut-off, the AUC of FNA-Tg/sTg ratio was 0.922 (95%CI: 0.889~0.955), and the sensitivity, specificity, positive predictive value, and negative predictive value were 82.7%, 95.5%, 85.3%, and 94.3%, respectively. The optimal diagnostic cut-off of FNA-Tg-sTg difference was determined to be >0; using this cut-off, the AUC of FNA-Tg-sTg difference was 0.841 (95%CI: 0.802~0.879), and the sensitivity, specificity, positive predictive value, and negative predictive value were 74.8%, 93.3%, 79.4%, and 91.5%, respectively.Conclusion:FNA-Tg can be used for the preoperative diagnosis of cervical lymph node metastasis in patients with papillary thyroid carcinoma. When 0.835 ng/ml is used as the cut-off value of FNA-Tg, the diagnostic performance is better. To avoid the possible impact of sTg level, FNA-Tg/sTg ratio and FNA-Tg-sTg difference could be used in combination.
As a result of their radiation-free nature and deep-penetration ability, tumor theranostics mediated by ultrasound have become increasingly recognized as a modality with high potential for translation into clinical cancer treatment. The effective integration of ultrasound imaging and sonodynamic therapy (SDT) into one nanoplatform remains an enormous challenge yet to be fully resolved. Here, a novel theranostic system, consisting of rattle-type SiO2 (r-SiO2) loaded with Mn-doped In2S3/InOOH (SMISO), was designed and synthesized to enable an improved ultrasound imaging-guided therapy. With Mn-doped In2S3/InOOH (MISO) and a heterojunction structure, this novel sonosensitizer facilitates the generation of reactive oxygen species (ROS) for SDT. By coupling interfaces between the shell and core in rattle-type SiO2, multiple reflections/scattering are generated, while MISO has high acoustic impedance. By integrating r-SiO2 and MISO, the SMISO composite nanoparticles (NPs) increase the acoustic reflection and provide enhanced contrast for ultrasound imaging. Through the effective accumulation in tumors, which was monitored by B-mode ultrasound imaging in vivo, SMISO composite NPs effectively inhibited tumor growth without adverse side effects under ultrasound irradiation treatment. This work therefore provides a new approach to integrate a novel gas-free ultrasound contrast agent and a semiconductor sonosensitizer for cancer theranostics.
Ultrasound targeted microbubble destruction (UTMD) was introduced as a promising method to improve anti-tumor therapeutic efficacy, while minimizing side effects to healthy tissues. Nevertheless, the acoustical phenomenon behind the UTMD as well as the exact mechanisms of autophagy action involved in the increased anti-cancer response are still not fully understood. Therefore, we examined the drug resistance-reversing effects of low-intensity focused ultrasound with microbubble (LIFU+MB) in paclitaxel (PTX)-resistant ovarian cancer cells. Cell viability was evaluated using CCK8 (Cell Counting Kit-8), apoptosis was detected by flow cytometry, quantitative real-time PCR and Western blot were used to detect the expressions of mRNA and protein, and autophagy was observed by transmission electron microscopy (TEM). We revealed that the level of autophagy was increased (p < 0.05) in PTX-resistant ovarian cancer cells. Treatment of LIFU+MB combined with PTX can notably inhibit proliferation as well as increase apoptosis (p < 0.01) in drug-resistant cells. We proposed that LIFU+MB might affect the sensitivity of ovarian cancer cells to PTX by modulating autophagy. To verify the hypothesis, we analyzed the autophagy level of drug-resistant cells after the treatment of LIFU+MB and found that autophagy was significantly inhibited. Altogether, our findings demonstrated that LIFU+MB could reverse PTX resistance in ovarian cancer via inhibiting autophagy, which provides a novel strategy to improve chemosensitivity in ovarian cancer.
Background: Glioma is a common type of tumor in the central nervous system characterized by high morbidity and mortality.Autophagy plays vital roles in the development and progression of glioma, and is involved in both normal physiological and various pathophysiological progresses.Patients and Methods: A total of 531 autophagy-related genes (ARGs) were obtained and 1738 glioma patients were collected from three public databases.We performed least absolute shrinkage and selection operator regression to identify the optimal prognosisrelated genes and constructed an autophagy-related risk signature.The performance of the signature was validated by receiver operating characteristic analysis, survival analysis, clinic correlation analysis, and Cox regression.A nomogram model was established by using multivariate Cox regression analysis.Schoenfeld's global and individual test were used to estimate time-varying covariance for the assumption of the Cox proportional hazard regression analysis.The R programming language was used as the main data analysis and visualizing tool.Results: An overall survival-related risk signature consisting of 15 ARGs was constructed and significantly stratified glioma patients into high-and low-risk groups (P < 0.0001).The area under the ROC curve of 1-, 3-, 5-year survival was 0.890, 0.923, and 0.889, respectively.Univariate and multivariate Cox analyses indicated that the risk signature was a satisfactory independent prognostic factor.Moreover, a nomogram model integrating risk signature with clinical information for predicting survival rates of patients with glioma was constructed (C-index=0.861±0.024). Conclusion:This study constructed a novel and reliable ARG-related risk signature, which was verified as a satisfactory prognostic marker.The nomogram model could provide a reference for individually predicting the prognosis for each patient with glioma and promoting the selection of optimal treatment.
Sonodynamic therapy (SDT), presenting spatial and temporal control of ROS generation triggered by ultrasound field, has attracted considerable attention in tumor treatment. However, its therapeutic efficacy is severely hindered by the intrinsic hypoxia of solid tumor and the lack of smart design in material band structure. Here in study, fine α-Fe2O3 nanoparticles armored with Pt nanocrystals (α-Fe2O3@Pt) was investigated as an alternative SDT agent with ingenious bandgap and structural design. The Schottky barrier, due to its unique heterostructure, suppresses the recombination of sono-induced electrons and holes, enabling superior ROS generation. More importantly, the composite nanoparticles may effectively trigger a reoxygenation phenomenon to supply sufficient content of oxygen, favoring the ROS induction under the hypoxic condition and its extra role played for ultrasound imaging. In consequence, α-Fe2O3@Pt appears to enable effective tumor inhibition with imaging guidance, both in vitro and in vivo. This study has therefore demonstrated a highly potential platform for ultrasound-driven tumor theranostic, which may spark a series of further explorations in therapeutic systems with more rational material design.
2020 年 9月 2 日,全国医学专业学位研究生教育指导委员会医专业学位委[2020]7 号文件"关于调整优化临床医学专业学位领域设置的通知"指出:为优化临床医学专业学位类别下的领域设置,进一步做好与住院医师规范化培训(以下简称"住培")科目对接工作,畅通临床医学人才培养路径,经国务院学位委员会办公室商定,就临床医学专业学位下设领域进行调整,其中影像医学与核医学调整为超声医学、放射影像学、核医学三个领域,为了适应新的形势,现将超声医学科住院医师规范化培训教学方式做一探讨.
Objective:To establish the prediction model of postoperative Gleason score (GS) risk of prostatic cancer (PCa), and to compare the diagnostic efficacy of the model and each independent risk factor for PCa medium-high risk group.Methods:The clinical data of 362 patients who accepted transrectal prostate biopsy in the Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine from January 2018 to December 2019 were analyzed retrospectively, and a total of 343 patients with prostate cancer who met the enrollment criteria were selected. According to the GS grading system, these patients were divided into low risk group, moderate risk group and high risk group. At first, the single factor analysis and Spearman rank correlation were used to find out the effective indicators with good correlation with GS risk. Then, multiple linear regression equation was applied for multi-factor analysis to obtain the independent risk factors and the prediction model for predicting GS risk, and then the ROC curve was used to compare the diagnostic efficacy of each independent risk factor and prediction model for PCa medium-high risk group.Results:In the single factor analysis, the differences of all indicators in GS risk were statistically significant (all P<0.05). In the correlation analysis with GS risk, except for the indicators of prostate volume (all P>0.05), the other indexes had linear correlations with the different risks of GS (all P<0.05). Among them, the total prostate specific antigen and two-dimensional ultrasound (2D-US) score showed moderate positive correlations( rs=0.402, 0.579, all P<0.001), contrast enhanced ultrasound (CEUS) score showed a high positive correlation ( rs=0.709, P<0.001), and the rest indexes showed low positive correlations. Multiple linear regression was used to obtain two independent risk factors of 2D-US score ( X1) and CEUS score ( X2) for the prediction of GS risk, then, a prediction model was established: Y=0.863+ 0.066 X1+ 0.27 X2, the corresponding linear coefficient differences were statistically significant(all P<0.05). By the ROC analysis, the areas under the curves of 2D-US score, CEUS score and the prediction model were 0.838, 0.906 and 0.907, respectively. Conclusions:2D-US score and CEUS score are independent risk factors for predicting postoperative GS risk, and the diagnostic efficacy of the prediction model is higher than those of the 2D-US score and CEUS score for the medium-high risk group.
Objective:To establish a predictive model of lateral lymph node metastasis in patients with papillary thyroid carcinoma(PTC), and further to compare the diagnostic efficiency of this model with the suspected abnormal lymph node thyroglobulin in fine-needle aspirate fluid (FNA-Tg) for lateral lymph node metastasis.Methods:The preoperative clinical and ultrasonographic data of 110 patients (257 lymph nodes) who underwent PTC cervical lymph node dissection were retrospectively analyzed. According to the postoperative pathological results, they were divided into lateral lymph node metastasis and non-metastasis group. Regression analysis was used to screen out independent risk factors affecting lateral lymph node metastasis and establish a predictive model. The ROC curve was used to evaluate the diagnostic efficacy and the best diagnostic cut-off point.Results:Prediction model: Logit( P)=-2.987+ 2.189(S/L ratio of lymph nodes)+ 1.748(hilum absent)+ 2.030(hyperechoic)+ 1.849(vascular abnormalities). The sensitivity, specificity, accuracy and AUC of the prediction model in the diagnosis of lateral lymph node metastasis were 92.1%, 83.9%, 87.9% and 0.929, respectively. The Homser-Lemeshow goodness of fit test showed that the Logistic model has a good fitting effect. The sensitivity, specificity, accuracy, and AUC of FNA-Tg in the diagnosis of lateral lymph node metastasis were 87.4%, 95.4%, 90.3% and 0.968, respectively. The sensitivity, specificity, accuracy, and AUC of the combined diagnosis of the predictive model and FNA-Tg were 92.9%, 96.9%, 94.2% and 0.989, respectively. Conclusions:The model has a good predictive value for PTC cervical lymph node metastasis. Combined with FNA-Tg, it can improve its diagnostic efficiency and provide more valuable information for the decision-making of clinical surgical procedures.
多形性脂肪肉瘤(Pleomorphic liposarcoma,PLS)是脂肪肉瘤中最罕见的亚型之一[1],好发于四肢近端的深部软组织,其次见于腹膜后[2-3],原发于胸壁的PLS罕见,文献报道其超声影像学表现较少.本文报道1例原发于胸壁的PLS超声影像学表现并结合相关文献进行复习.
Introduction: Multispectral imaging (MSI) shows increasing strengths in detection of retinal and choroidal disease. The aim of this study was to evaluate the capacity of javascript: void(0), detecting retinal and choroidal abnormalities of uveitis which have not been described previously. Patient concerns: The first case was a 49-year-old male patient who presented with visual disturbance and metamorphopsia in both eyes for 5 days, companying by a history of headache and hearing loss recently. The second case was related to a 45-year-old female patient who complained of blurred vision and a dark shadow before her right eye for 3 months. The third case corresponded to a 36-year-old male patient who presented with blurred vision and slight pain in his left eye for >1 week, and his blood tested positive for syphilis. Diagnosis: Three Chinese patients with representative kind of uveitis were described in the study, including Vogt-Koyanagi-Harada syndrome, posterior uveitis with choroidal neovascularization, and syphilis-infected uveitis. Each affected eye had corresponding retinal and choroidal abnormalities evaluated by multiple ophthalmologic examinations. Interventions: Case 1 was treated with oral prednisone at a dose of 1mg/kg/d started at the early stage and then slowed tapering of the prednisone dose based on follow-up examinations. Case 2 received anti-VEGF treatment. Case 3 received the standard treatment for neurosyphilis. Outcomes: Due to timely diagnosis and treatment, all patients had a better prognosis. Conclusion: MSI provides a novel way to view retinal and choroidal abnormalities of uveitis, and may provide a supplemental method to morphological changes.
Photonic cancer hyperthermia has been considered to be one of the most representative noninvasive cancer treatments with high therapeutic efficiency and biosafety. However, it still remains a crucial challenge to develop efficient photothermal nanoagents with satisfactory photothermal performance and biocompatibility, among which two-dimensional (2D) ultrathin nanosheets have recently been regarded as the promising multifunctional theranostic agents for photothermal tumor ablation. In this work, we report, for the first time, on the construction of a novel kind of photothermal agents based on the intriguing 2D antimony(III) selenide (Sb2Se3) nanosheets for highly efficient photoacoustic imaging-guided photonic cancer hyperthermia by near-infrared (NIR) laser activation. These Sb2Se3 nanosheets were easily fabricated by a novel but efficiently combined liquid nitrogen pretreatment and freezing-thawing approach, which were featured with high photothermal-conversion capability (extinction coefficient: 33.2 L g-1 cm-1; photothermal-conversion efficiency: 30.78%). The further surface engineering of these Sb2Se3 ultrathin nanosheets with poly(vinyl pyrrolidone) (PVP) substantially improved the biocompatibility of the nanosheets and their stability in physiological environments, guaranteeing the feasibility in photonic antitumor applications. Importantly, 2D Sb2Se3-PVP nanosheets have been certificated to efficiently eradicate the tumors by NIR-triggered photonic tumor hyperthermia. Especially, the biosafety in vitro and in vivo of these Sb2Se3 ultrathin nanosheets has been evaluated and demonstrated. This work meaningfully expands the biomedical applications of 2D bionanoplatforms with a planar topology through probing into new members (Sb2Se3 in this work) of 2D biomaterials with unique intrinsic physiochemical property and biological effect.
Objective To evaluate the correlation between ultrasound features of papillary thyroid carcinoma(PTC)and lymph node metastasis by preoperative ultrasound elemental observation of thyroid nodules.Methods Three hundred and seventy-six patients who underwent primary thyroid surgery and confirmed by ultrasound and pathological data as single-focal PTC from Jannary to December 2017 in Sir Run Run Shaw Hospital of Zhejiang Univbersity College of Medicine were retrospectively analyzed. According to the presence or absence of lymph node metastasis,they were divided into central and lateral lymph node metastasis group and non-metastasis group.Independent risk factors for central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) were analyzed byχ2 test and multivariate Logistic regression.Results Multivariate analysis showed that the posterior margin of the cancer was <0.25 cm from the posterior wall of the thyroid gland as an independent risk factor for CLNM(P=0.025). Compared with the tumor volume ≤0.38 cm3 ,the cancer volume >0.38 cm3(P=0.000),was more prone to CLNM.And multivariate analysis showed that the anterior margin of the cancer was <0.17 cm(P =0.006)from the anterior thyroid capsule and the inner wall of the foci was <0.26 cm (P =0.014) as independent risk factors for LLNM.Compared with the maximum diameter of the tumor lesion ≤1 cm,the maximum diameter >2 cm (P =0.001) group was more prone to LLNM.Compared with the tumor volume ≤0.38 cm3 ,the tumor volume >0.38 cm3(P =0.000)was more prone to LLNM.ConclusionsThe larger volume of single focal PTC carcinoma and the closer to the posterior thyroid capsule are independent risk factors for CLNM.The larger volume and diameter of single focal PTC,and the closer to the anterior and medial wall capsule are independent risk factors for LLNM.
Objective To investigate the sonographic features and diagnosis values of struma ovarii. Methods The sonographic features of 20 struma ovarii patients diagnosed by pathology from June 2015 to March 2018 were retrospectively analyzed. Results The age of the patients was 29 to 82 (41.5 ± 24.0) years old, and 5 cases were postmenopausal. Ultrasonography showed that ovarian goiter was mainly unilateral and solid-cystic, and most of them were thick partitions. The solid echo was similar to the thyroid gland, and more specific papillary protrusions and honeycomb structures could be found. Some of them could show crystallization speckle echo (high probability of cystic part), and blood flow signal could be seen in most of solid part. The pathological results showed that all cases were ovarian goiter except 1 case of ovarian goiter with local papillary thyroid carcinoma. Conclusions Struma ovarii is characteristic to a certain extent, and ultrasonography is helpful for the diagnosis of the disease.