Corrigendum: Ultrasound-based radiomics analysis for differentiating benign and malignant breast lesions: from static images to CEUS video analysis.

[This corrects the article DOI: 10.3389/fonc.2022.951973.].

Intramedullary administration of tranexamic acid reduces bleeding in proximal femoral nail antirotation surgery for intertrochanteric fractures in elderly individuals: A randomized controlled trial.

PURPOSE: Intertrochanteric fractures undergoing proximal femoral nail antirotation (PFNA) surgery are associated with significant hidden blood loss. This study aimed to explore whether intramedullary administration of tranexamic acid (TXA) can reduce bleeding in PFNA surgery for intertrochanteric fractures in elderly individuals. METHODS: A randomized controlled trial was conducted from January 2019 to December 2022. Patients aged over 60 years with intertrochanteric fractures who underwent intramedullary fixation surgery with PFNA were eligible for inclusion and grouped according to random numbers. A total of 249 patients were initially enrolled, of which 83 were randomly allocated to the TXA group and 82 were allocated to the saline group. The TXA group received intramedullary perfusion of TXA after the bone marrow was reamed. The primary outcomes were total peri-operative blood loss and post-operative transfusion rate. The occurrence of adverse events was also recorded. Continuous data was analyzed by unpaired t-test or Mann-Whitney U test, and categorical data was analyzed by Pearson Chi-square test. RESULTS: The total peri-operative blood loss (mL) in the TXA group was significantly lower than that in the saline group (577.23 ± 358.02 vs. 716.89 ± 420.30, p = 0.031). The post-operative transfusion rate was 30.67 % in the TXA group and 47.95 % in the saline group (p = 0.031). The extent of post-operative deep venous thrombosis and the 3-month mortality rate were similar between the 2 groups. CONCLUSION: We observed that intramedullary administration of TXA in PFNA surgery for intertrochanteric fractures in elderly individuals resulted in less peri-operative blood loss and decreased transfusion rate, without any adverse effects, and is, thus, recommended.

Improving the anti-tumor effect of EGCG in colorectal cancer cells by blocking EGCG-induced YAP activation.

(-)-Epigallocatechin-3-gallate (EGCG) is the primary active ingredient in green tea and has been used for cancer prevention in clinical trials. The anti-tumor effects of EGCG stem from its ability to inhibit the activities of many oncoproteins, such as AKT, VEGFR, STAT3, and mutant p53. However, the clinical efficacy of EGCG is unsatisfactory. How to improve the anti-tumor effects of EGCG is an open question. Here we report that EGCG inhibits the tumor suppressive Hippo signaling pathway and activates downstream YAP in colorectal cancer (CRC) cells. Activation of YAP impedes the anti-tumor effects of EGCG. YAP blockade increases the sensitivity of CRC cells to EGCG treatment.

Multimodal ultrasound features of breast cancers: correlation with molecular subtypes.

OBJECTIVES: To investigate whether multimodal intratumour and peritumour ultrasound features correlate with specific breast cancer molecular subtypes. METHODS: From March to November 2021, a total of 85 patients with histologically proven breast cancer underwent B-mode, real-time elastography (RTE), colour Doppler flow imaging (CDFI) and contrast-enhanced ultrasound (CEUS). The time intensity curve (TIC) of CEUS was obtained, and the peak and time to peak (TTP) were analysed. Chi-square and binary logistic regression were used to analyse the connection between multimodal ultrasound imaging features and breast cancer molecular subtype. RESULTS: Among 85 breast cancers, the subtypes were as follows: luminal A (36 cases, 42.4%), luminal B (20 cases, 23.5%), human epidermal growth factor receptor-2 positive (HER2+) (16 cases, 18.8%), and triple negative breast cancer (TNBC) (13 cases, 15.3%). Binary logistic regression models showed that RTE (P < 0.001) and CDFI (P = 0.036) were associated with the luminal A cancer subtype (C-index: 0.741), RTE (P = 0.016) and the peak ratio between intratumour and corpus mamma (P = 0.036) were related to the luminal B cancer subtype (C-index: 0.788). The peak ratio between peritumour and intratumour (P = 0.039) was related to the HER2 + cancer subtype (C-index: 0.859), and CDFI (P = 0.002) was associated with the TNBC subtype (C-index: 0.847). CONCLUSIONS: Multimodal ultrasound features could be powerful predictors of specific breast cancer molecular subtypes. The intra- and peritumour CEUS features play assignable roles in separating luminal B and HER2 + breast cancer subtypes.

Ultrasound-based radiomics analysis for differentiating benign and malignant breast lesions: From static images to CEUS video analysis.

Background: Continuous contrast-enhanced ultrasound (CEUS) video is a challenging direction for radiomics research. We aimed to evaluate machine learning (ML) approaches with radiomics combined with the XGBoost model and a convolutional neural network (CNN) for discriminating between benign and malignant lesions in CEUS videos with a duration of more than 1 min. Methods: We gathered breast CEUS videos of 109 benign and 81 malignant tumors from two centers. Radiomics combined with the XGBoost model and a CNN was used to classify the breast lesions on the CEUS videos. The lesions were manually segmented by one radiologist. Radiomics combined with the XGBoost model was conducted with a variety of data sampling methods. The CNN used pretrained 3D residual network (ResNet) models with 18, 34, 50, and 101 layers. The machine interpretations were compared with prospective interpretations by two radiologists. Breast biopsies or pathological examinations were used as the reference standard. Areas under the receiver operating curves (AUCs) were used to compare the diagnostic performance of the models. Results: The CNN model achieved the best AUC of 0.84 on the test cohort with the 3D-ResNet-50 model. The radiomics model obtained AUCs between 0.65 and 0.75. Radiologists 1 and 2 had AUCs of 0.75 and 0.70, respectively. Conclusions: The 3D-ResNet-50 model was superior to the radiomics combined with the XGBoost model in classifying enhanced lesions as benign or malignant on CEUS videos. The CNN model was superior to the radiologists, and the radiomics model performance was close to the performance of the radiologists.

Expression and potential role of FOSB in glioma.

Background: FOSB is reported to be an oncogene in a variety of tumors. However, the expression and role of FOSB in glioma remain obscure. In this study, we aimed to explore the expression of FOSB in glioma and its biological role in glioblastoma multiforme (GBM). Methods: Western blot, immunohistochemical staining, and quantitative real-time polymerase chain reaction (RT-qPCR) were used to detect the expression of FOSB in clinical samples. FOSB was knocked down in cells to determine the effects of FOSB on the phenotypic changes of tumors by plate cloning, CCK-8 assay, and Transwell assay. Finally, subcutaneous tumorigenesis in nude mice was used to observe the tumorigenesis of glioma cell lines after the knockdown of the FOSB gene. Results: FOSB expression was higher in glioma compared with normal brain tissue. After the downregulation of FOSB, the expression of cleaved caspase-3 increased. Plate cloning and CCK-8 experiments showed that the proliferation of glioma cell lines decreased. The Transwell assay demonstrated that the glioblastoma cell lines had lower migration ability after the knockdown of FOSB. Finally, the tumor volume of U87 glioma cells in group sh-FOSB was smaller than that in the control group. The TUNEL staining in vitro showed that the apoptosis of sh-FOSB glioma cells increased. Conclusion: FOSB was highly expressed in glioma tissues. The viability of glioma cells decreased, and the ability of glioma cells to proliferate and migrate was reduced when FOSB was downregulated. Hence, FOSB may promote the development and migration of gliomas.

Inhibition of TRPA1 Attenuates Oxidative Stress-induced Damage After Traumatic Brain Injury via the ERK/AKT Signaling Pathway.

Neuron apoptosis is a feature of secondary injury after traumatic brain injury (TBI). Evidence implies that excess calcium (Ca2+) ions and reactive oxidative species (ROS) play critical roles in apoptosis. In reaction to increased ROS, the anti-oxidative master transcription factor, Transient receptor potential Ankyrin 1 (TRPA1) allows Ca2+ ions to enter cells. However, the effect of TBI on the expression of TRPA1 and the role of TRPA1 in TBI are unclear. In the present study, TBI in the mouse brain was simulated using the weight-drop model. The process of neuronal oxidative stress was simulated in HT22 neuronal cells by treatment with hydrogen peroxide. We found that TRPA1 was significantly upregulated in neurons at 24 h after TBI. Neuronal apoptosis was increased in the in vivo and in vitro models; however, this increase was reduced by the functional inhibition of TRPA1 in both models. After TBI, TRPA1 was upregulated via nuclear factor, erythroid 2 like 2 (Nrf2) in neurons. TRPA1-mediated neuronal apoptosis after TBI might be achieved in part through the CaMKII/AKT/ERK signaling pathway. To sum up, TBI-triggered TRPA1 upregulation in neurons is mediated by Nrf2 and the functional blockade of TRPA1 attenuates neuronal apoptosis and improves neuronal dysfunction, partially mediated through the activation of the calcium/calmodulin dependent protein kinase II (CaMKII) extracellular regulated kinase (ERK)/protein kinase B (AKT) signaling pathway. Our results suggest that functional blockade of TRPA1 might be a promising therapeutic intervention related to ROS and Nrf2 in TBI.

SIRT1 Promotes M2 Microglia Polarization via Reducing ROS-Mediated NLRP3 Inflammasome Signaling After Subarachnoid Hemorrhage.

Mounting evidence has suggested that modulating microglia polarization from pro-inflammatory M1 phenotype to anti-inflammatory M2 state might be a potential therapeutic approach in the treatment of subarachnoid hemorrhage (SAH) injury. Our previous study has indicated that sirtuin 1 (SIRT1) could ameliorate early brain injury (EBI) in SAH by reducing oxidative damage and neuroinflammation. However, the effects of SIRT1 on microglial polarization and the underlying molecular mechanisms after SAH have not been fully illustrated. In the present study, we first observed that EX527, a potent selective SIRT1 inhibitor, enhanced microglial M1 polarization and nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation in microglia after SAH. Administration of SRT1720, an agonist of SIRT1, significantly enhanced SIRT1 expression, improved functional recovery, and ameliorated brain edema and neuronal death after SAH. Moreover, SRT1720 modulated the microglia polarization shift from the M1 phenotype and skewed toward the M2 phenotype. Additionally, SRT1720 significantly decreased acetylation of forkhead box protein O1, inhibited the overproduction of reactive oxygen species (ROS) and suppressed NLRP3 inflammasome signaling. In contrast, EX527 abated the upregulation of SIRT1 and reversed the inhibitory effects of SRT1720 on ROS-NLRP3 inflammasome activation and EBI. Similarly, in vitro, SRT1720 suppressed inflammatory response, oxidative damage, and neuronal degeneration, and improved cell viability in neurons and microglia co-culture system. These effects were associated with the suppression of ROS-NLRP3 inflammasome and stimulation of SIRT1 signaling, which could be abated by EX527. Altogether, these findings indicate that SRT1720, an SIRT1 agonist, can ameliorate EBI after SAH by shifting the microglial phenotype toward M2 via modulation of ROS-mediated NLRP3 inflammasome signaling.

Atorvastatin combined with dexamethasone in chronic subdural haematoma (ATOCH II): study protocol for a randomized controlled trial.

BACKGROUND: Chronic subdural haematoma (CSDH) is a common condition in the elderly that often requires neurosurgical management. For small CSDH, evidence has emerged that statins may reduce haematoma volume and improve outcomes, presumably by reducing local inflammation and promoting vascular repair. We wish to extend this evidence in a study that aims to determine the efficacy and safety of atorvastatin combined with low-dose dexamethasone in patients with CSDH. METHODS: The second ATorvastatin On Chronic subdural Hematoma (ATOCH-II) study is a multi-centre, randomized, placebo-controlled, double-blind trial which aims to enrol 240 adult patients with a conservative therapeutic indication for CSDH, randomly allocated to standard treatment with atorvastatin 20 mg combined with low-dose dexamethasone (or matching placebos) daily for 28 days, and with 152 days of follow-up. The primary outcome is a composite good outcome defined by any reduction from baseline in haematoma volume and survival free of surgery at 28 days. Secondary outcomes include functional outcome on the modified Rankin scale (mRS) and modified Barthel Index at 28 days, surgical transition and reduction in haematoma volumes at 14, 28 and 90 days. DISCUSSION: This multi-centre clinical trial aims to provide high-quality evidence on the efficacy and safety of the combined treatment of atorvastatin and low-dose dexamethasone to reduce inflammation and enhance angiogenesis in CSDH. TRIAL REGISTRATION: ChiCTR, ChiCTR1900021659 . Registered on 3 March 2019, http://www.chictr.org.cn/showproj.aspx?proj=36157 .

[Preliminary research of deqi and the tissue depth of acupoint thread embedding therapy on weight reduction under ultrasonic guidance].

OBJECTIVE: To explore the impacts on weight reduction effect treated with acupoint thread embedding therapy at different tissue levels under ultrasonic guidance. METHODS: A total of 70 patients with overweight or obesity were randomized into a shallow-tissue thread embedding group (35 cases, 5 cases dropped off) and a deep-tissue thread embedding group (35 cases, 4 cases dropped off). Under ultrasonic guidance, the thread was embedded in the shallow tissue level and the deep tissue level respectively. The acupoints were Zhongwan (CV 12), Xiawan (CV 10), Shuifen (CV 9), Zhongji (CV 3), etc. The thread embedding therapy was exerted once every 2 weeks, totally for 3 times. Before and 2 weeks after treatment, body mass, body mass index (BMI), waist circumference and hip circumference were recorded in the patients of the two groups separately. After each treatment, the number and the property of blood vessels under each acupoint were detected by ultrasound. Besides, the needling sensation and the intensity were scored and the adverse events were observed after thread embedding therapy. RESULTS: After treatment, the reduction range of body mass, BMI and waist circumference in the deep-tissue thread embedding group were larger than those in the shallow-tissue thread embedding group successively (P<0.05). The scores of distention and fullness sensation, needling sensation and intensity in the deep-tissue thread embedding group were higher than those in the shallow-tissue thread embedding group successively (P<0.05). Of 29 cases in the shallow-tissue thread embedding group and 27 cases of the deep-tissue thread embedding group, under at least one acupoint, the vessels were found and distributed unevenly (P<0.05). There were no adverse events, i.e. bleeding and infection in the two groups. CONCLUSION: The deep-tissue thread embedding therapy achieves the stronger deqi (needling sensation) and better effect of weight reduction. The acupoint thread embedding therapy under ultrasonic guidance can accurately locate the tissue depth and reduce the incidence of adverse events of thread embedding treatment.

FOXO4 expression associates with glioblastoma development and FOXO4 expression inhibits cell malignant phenotypes in vitro and in vivo.

BACKGROUND AND AIM: Forkhead box protein O4 (FOXO4) is a transcription factor, and aberrant FOXO4 expression is associated with development of various human cancers. This study explored the role of FOXO4 in glioma in vitro and in vivo. METHODS: FOXO4 expression was first assessed in normal brain tissues, low-grade glioma, glioblastoma multiforme (GBM), normal human astrocytes (HA), and GBM cell lines, while manipulation of FOXO4 expression in glioma cell lines was assessed using qRT-PCR, Western blot, and cell viability CCK-8, Transwell, and a nude mouse subcutaneous xenograft assays. KEY FINDINGS: The data showed downregulated FOXO4 expression in GBM tissues and cell lines. FOXO4 overexpression induced by transfection with FOXO4 cDNA significantly inhibited GBM cell proliferation, migration, and invasion, but increased tumor cells to undergo apoptosis in vitro, while suppressed growth of GBM cell subcutaneous xenografts in nude mice. In conclusion, FOXO4 possesses an anti-cancer glioma activity, which could be a novel target for future control of GBM.

Ghrelin alleviates traumatic brain injury-induced acute lung injury through pyroptosis/NF-κB pathway.

Acute lung injury (ALI) is one of the severe complications in patients with traumatic brain injury (TBI), contributing to the high mortality. Ghrelin has protective effects against various inflammatory diseases, but the effects of Ghrelin on TBI-induced ALI and its mechanisms remain unknown. In this study, Ghrelin administration was performed on the mice with TBI, then histological change in cortex and lung tissues, lung vascular permeability and macrophage number in bronchoalveolar lavage fluid (BALF) were examined, respectively. Simultaneously, the alterations of proinflammatory factors and pyroptosis-related proteins in lung tissues were detected. As a result, TBI-induced ALI was ameliorated after Ghrelin treatment, which was demonstrated by improved histology, reduced lung vascular permeability, and peripheral macrophage number. Furthermore, Ghrelin decreased the mRNA levels of proinflammatory factors (IL-1ß, IL-6, TNF-α and IL-18), the protein levels of pyroptosis-related proteins (NLRP3, Caspase1-P20, HMGB1 and Gasdermin D), and the phosphorylation levels of NF-κB in lung tissues. These results showed that Ghrelin attenuating TBI-induced ALI might be via ameliorating inflammasome-induced pyroptosis by blocking NF-κB signal, which are important for the prevention and treatment of TBI-induced ALI.

S100A8 Promotes Inflammation via Toll-Like Receptor 4 After Experimental Traumatic Brain Injury.

INTRODUCTION: S100 calcium-binding protein A8 (S100A8) is also known as macrophage-related protein 8, which is involved in various pathological processes in the central nervous system post-traumatic brain injury (TBI), and plays a critical role in inducing inflammatory cytokines. Accumulating evidences have indicated that toll-like receptor 4 (TLR4) is considered to be involved in inflammatory responses post TBI. The present study was designed to analyze the hypothesis that S100A8 is the key molecule that induces inflammation via TLR4 in TBI. METHODS: The weight-drop TBI model was used and randomly implemented on mice that were categorized into six groups: Sham, NS, S100A8, S100A8+TAK-242, TBI, and TBI+TAK-242 groups. In the S100A8+TAK-242 and TBI+TAK-242 groups, at half an hour prior to the intracerebroventricular administration of S100A8 or TBI, mice were intraperitoneally treated with TAK-242 that acts as a selective antagonist and inhibitor of TLR4. Furthermore, the protein recombinant of S100A8 was injected into the lateral ventricle of the brain of mice in the S100A8 and S100A8+TAK-242 groups. Sterile normal saline was injected into the lateral ventricle in the NS group. To evaluate the association between S100A8 and TLR4, Western blot, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Nissl staining were employed. Simultaneously, the neurological score and brain water content were assessed. In the in vitro analysis, BV-2 microglial cells were stimulated with lipopolysaccharide LPS or S100A8 recombinant protein, with or without TAK-242. The expression of the related proteins was subsequently detected by Western blot or enzyme-linked immunosorbent assay. RESULTS: The levels of S100A8 protein and pro-inflammatory cytokines were significantly elevated after TBI. There was a reduction in the neurological scores of non-TBI animals with remarkable severe brain edema after the intracerebroventricular administration of S100A8. Furthermore, the TLR4, p-p65, and myeloid differentiation factor 88 (MyD88) levels were elevated after the administration of S100A8 or TBI, which could be restored by TAK-242. Meanwhile, in the in vitro analysis, due to the stimulation of S100A8 or LPS, there was an upregulation of p-p65 and MyD88, which could also be suppressed by TAK-242. CONCLUSION: The present study demonstrated that the TLR4-MyD88 pathway was activated by S100A8, which is essential for the development of inflammation in the brain after TBI.

Clinical and radiological factors predicting recurrence of chronic subdural hematoma: A retrospective cohort study.

BACKGROUND: Chronic subdural hematoma (CSDH) is commonly encountered in the elderly patients and the recurrence rate is still high, therefore, identifying risk factors for CSDH recurrence is essential. The present study aimed to identify clinical and radiological factors predicting the recurrence of CSDH. METHODS: We retrospectively identified 461 patients with CSDH who underwent surgical evacuation in our department. Univariable analyses were performed at first, variables with a P-value of <0.05 were entered into multivariable logistic regression model. Kendall's tau-b test was used to evaluate the relationship between brain atrophy and postoperative pneumocephalus. RESULTS: Univariable analyses revealed that patients with the following characteristics have a higher recurrence rate, including age ≥80 years, antiplatelet and/or anticoagulant use, GOS = 3, the volume of drainage ≥100 ml, midline shift ≥10 mm, severe brain atrophy, severe postoperative pneumocephalus. Multivariable logistic regression demonstrated that midline shift ≥10 mm, severe brain atrophy, severe postoperative pneumocephalus, and volume of drainage ≥100 ml were independent risk factors for CSDH recurrence. Kendall's tau-b test revealed that there was no correlation between brain atrophy and postoperative pneumocephalus. CONCLUSIONS: Midline shift ≥10 mm, severe brain atrophy, severe postoperative pneumocephalus, and volume of drainage ≥100 ml were independent risk factors for CSDH recurrence, CSDH patients with these characteristics should be taken precautions of recurrence and a closely follow-up should be carried out.

Cerebral Syphilitic Gumma Misdiagnosed as a Malignant Brain Tumor.

Syphilitic gumma involvement of the central nervous system is extremely rare and frequently misdiagnosed. The authors report a patient of a cerebral syphilitic gumma resembling a malignant brain tumor in a 62-year-old male. He was first suspected of a malignant brain tumor, but the pathological diagnosis was cerebral syphilitic gumma. This patient with unusual findings illustrates the clinical manifestations, imaging, and therapeutic aspects of cerebral syphilitic gumma.

Expression and functional significance of ezrin in human brain astrocytoma.

Ezrin is overexpressed in a variety of neoplastic cells and is involved in the later stages of tumor progression and metastasis. The present study investigated the expression and functional significance of ezrin in human brain astrocytoma. Ezrin expression was examined in specimens from healthy human brains (10 autopsies) or human astrocytoma (107 cases) by immunohistochemistry. All healthy specimens were negative for ezrin expression, while this expression was positive in a great majority of human astrocytoma tissues (96/107; 89.7%; p < 0.05 vs. healthy). Ezrin expression was positively correlated with tumor grade (r = 0.551, p < 0.01). Analysis of clinicopathologic data revealed that the post-operation disease-free survival times were significantly (p < 0.001) different between those with a strong positive ezrin expression and those with a weak or negative expression. Specifically, median DFS in patients with a strongly positive ezrin expression was 13 months (range 2-46 months), while it was significantly (p < 0.001) longer in patients with weakly positive or negative expression (median of 28 months, range 6-56 months). In conclusion, there is a strong association between ezrin expression and increased malignancy in astrocytoma. Thus, enhanced ezrin expression may play an important role in the development of astrocytoma. Our results further indicate that ezrin may be useful for grading of astrocytoma and as a molecular marker for the prognosis.