A Comprehensive Model Outperformed the Single Radiomics Model in Noninvasively Predicting the HER2 Status in Patients with Breast Cancer.

RATIONALE AND OBJECTIVES: This study aimed to develop predictive models based on conventional magnetic resonance imaging (cMRI) and radiomics features for predicting human epidermal growth factor receptor 2 (HER2) status of breast cancer (BC) and compare their performance. MATERIALS AND METHODS: A total of 287 patients with invasive BC in our hospital were retrospectively analyzed. All patients underwent preoperative breast MRI consisting of fat-suppressed T2-weighted imaging, axial dynamic contrast-enhanced MRI, and diffusion-weighted imaging sequences. From these sequences, radiomics features were derived. Three distinct models were established utilizing cMRI features, radiomics features, and a comprehensive model that amalgamated both. The predictive capabilities of these models were assessed using the receiver operating characteristic curve analysis. The comparative performance was then determined through the DeLong test and net reclassification improvement (NRI). RESULTS: In a randomized split, the 287 patients with BC were allotted to either training (234; 46 HER2-zero, 107 HER2-low, 81 HER2-positive) or test (53; 8 HER2-zero, 27 HER2-low, 18 HER2-positive) at an 8:2 ratio. The mean area under the curve (AUCs) for cMRI, radiomics, and comprehensive models predicting HER2 status were 0.705, 0.819, and 0.859 in training set and 0.639, 0.797, and 0.842 in test set, respectively. DeLong's test indicated that the combined model's AUC surpassed the radiomics model significantly (p < 0.05). NRI analysis verified superiority of the combined model over the radiomics for BC HER2 prediction (NRI 25.0) in the test set. CONCLUSION: The comprehensive model based on the combination of cMRI and radiomics features outperformed the single radiomics model in noninvasively predicting the three-tiered HER2 status in patients with BC.

EGFR mutations and abnormal trafficking in cancers.

Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor and a member of the ErbB receptor family. As a significant cancer driver, EGFR undergoes mutations such as gene amplification or overexpression in a wide range of malignant tumors and is closely associated with tumorigenesis. This review examines the aberrant expression of EGFR in several common cancers and summarizes the current therapeutic strategies developed for this receptor. Additionally, this review compares the differences in EGFR activation, internalization, endocytosis, and sorting in normal and cancer cells, and highlights some regulatory factors that influence its trafficking process.Kindly check and confirm the edit made in the title.Yes, correctAs per journal instructions structured abstract is mandatory kindly provideThe abstract format does not apply to Review articles.

Bilateral axillo-breast approach robotic thyroglossal duct cyst resection in an adolescent: a case report and literature review.

Background: Thyroglossal duct cyst (TGDC) is a common congenital neck mass that is the most frequent cause of neck swelling in children. The traditional open Sistrunk procedure for TGDC often leaves a visible scar on the neck. Therefore, it is essential to consider the impact of neck scarring on the quality of life for children and adolescents. Our study aimed to assess the safety and efficacy of robotic TGDC resection using the bilateral axillo-breast approach (BABA) in adolescents. Case Description: A 16-year-old female patient presented with a neck mass (no pain or redness) that had been present for 3 years. The palpable neck mass moved with swallowing and there was no history of other significant medical conditions. An ultrasound scan of the neck indicated a weak hypoechoic area in the thyrohyoid region measuring 29 mm × 20 mm. Additionally, the ultrasonography of the thyroid gland showed no obvious abnormalities. A computer tomography (CT) scan confirmed a low-density lesion on the right hyoid bone, measuring 27 mm × 18 mm × 26 mm, consistent with a TGDC. We successfully performed a BABA robotic TGDC resection on the 16-year-old female adolescent who had a strong desire for scar-free surgery. Conclusions: BABA robotic TGDC resection could achieve the same surgical effect as conventional open surgery while providing better cosmetic outcomes, which are essential for the physical and mental well-being of teenagers. Therefore, BABA robotic TGDC resection may be a safe and feasible treatment option with excellent cosmetic results in adolescents.

Structural and Property Characterizations of Dual-Responsive Core-Shell Tecto Dendrimers for Tumor Penetration and Gene Delivery Applications.

Core-shell tecto dendrimers (CSTDs) with excellent physicochemical properties and good tumor penetration and gene transfection efficiency have been demonstrated to have the potential to replace high-generation dendrimers in biomedical applications. However, their characterization and related biological properties of CSTDs for enhanced tumor penetration and gene delivery still lack in-depth investigation. Herein, three types of dual-responsive CSTDs are designed for thorough physicochemical characterization and investigation of their tumor penetration and gene delivery efficiency. Three types of CSTDs are prepared through phenylborate ester bonds of phenylboronic acid (PBA)-decorated generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers as cores and monose (galactose, glucose, or mannose)-conjugated G3 PAMAM dendrimers as shells and thoroughly characterized via NMR and other techniques. It is shown that the produced CSTDs display strong correlation signals between the PBA and monose protons, similar hydrodynamic diameters, and dual reactive oxygen species- and pH-responsivenesses. The dual-responsive CSTDs are proven to have structure-dependent tumor penetration property and gene delivery efficiency in terms of small interference RNA for gene silencing and plasmid DNA for gene editing, thus revealing a great potential for different biomedical applications.

Heterologous synthesis of ginsenoside F1 and its precursors in Nicotiana benthamiana.

Ginsenoside F1 has high medicinal values, which is a kind of rare triterpene saponin isolated from Panax plants. The extremely low content of ginsenoside F1 in herbs has limited its research and application in medical field. In this work, we constructed a pathway in tobacco for the biosynthesis of ginsenoside F1 by metabolic engineering. Four enzyme genes (PnDDS, CYP716A47, CYP716S1 and UGT71A56) isolated from Panax notoginseng were introduced into tobacco. Thus, a biosynthetic pathway for ginsenoside F1 synthesis was artificially constructed in tobacco cells; moreover, the four exogenous genes could be expressed in the roots, stems and leaves of transgenic plants. Consequently, ginsenoside F1 and its precursors were successfully synthesized in the transgenic tobacco, compared with Panax plants, the content of ginsenoside F1 in transgenic tobacco was doubled. In addition, accumulation of ginsenoside F1 and its precursors in transgenic tobacco shows organ specificity. Based on these results, a new approach was established to produce rare ginsenoside F1; meanwhile, such strategy could also be employed in plant hosts for the heterologous synthesis of other important or rare natural products.

Combined treatment with cetuximab and STA9090 has synergistic anticancer effects on human non-small cell lung cancer.

Cetuximab (CET), a human murine chimeric IgG monoclonal antibody and an inhibitor of epidermal growth factor receptor (EGFR), has been shown to be effective in treating various types of cancer. However, its use is hindered by limitations such as resistance development, variability in patient response, side effects, and challenges in biomarker identification. Therefore, CET is often combined with other targeted therapies or chemotherapies to enhance its effectiveness. In this study, we investigate the anticancer effects and underlying mechanisms of the combination of CET, an EGFR inhibitor, and STA9090, an inhibitor of heat shock protein 90 (Hsp90), in both in vitro and in vivo models of non-small cell lung cancer (NSCLC). The results demonstrate significantly stronger effects on NSCLC cells in response to combination therapy than to treatment with either agent alone, indicating that the combination of CET and STA9090 has potential synergistic effects. Additionally, the combination therapy inhibits tumor growth in a xenograft nude mouse model more effectively than treatment with either agent alone, suggesting improved efficacy when used together. Furthermore, the synergistic effects of the combination therapy are likely due to inactivation of the receptor tyrosine kinase (RTK) pathway, which is overly activated in cancer and contributes to tumor growth, angiogenesis, and metastasis. Consequently, our findings suggest that STA9090 has potent direct antitumor activity and synergizes with CET against NSCLC tumors. It is highly likely that these synergistic effects are mediated through RTK pathway inactivation caused by the combination. Therefore, our findings strongly and consistently support the potential synergistic effect of STA9090, an RTK inhibitor, in combination with EGFR-targeting agents.

Lumboperitoneal shunt and ventriculoperitoneal shunt for chronic hydrocephalus after aneurysmal subarachnoid hemorrhage: a comparison.

Objective: Chronic hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH) results in poor neurological outcomes and cognitive deficits. Currently, the main treatments for chronic hydrocephalus include ventriculoperitoneal shunt (VPS) and lumboperitoneal shunt (LPS); however, the optimal treatment for chronic hydrocephalus after aSAH remains controversial. Method: The records of 82 patients were retrospectively analyzed, and the patients were divided into VPS and LPS groups based on surgical methods. The efficacy, shunt successful rate and complications were compared. The assessments of treatment efficacy included the Evans index score (EIS), Keifer's hydrocephalus score (KHS), Mini-Mental State Examination (MMSE) score and functional independence measure (FIM). Patients were followed up for three months to observe the postoperative curative effects and complications. Results: The rate of shunt obstruction was significantly higher in the LPS group than that in the VPS group (p < 0.05), and the shunt successful rate was significantly higher in the VPS group than that in the LPS group (p < 0.05). The total rate of complications was 24.4% for LPS and 39% for VPS. The improvements in EIS, KHS, MMSE, and FIM within each group after the shunt were significantly different compared to those before shunt (p < 0.05). Compared to those in the LPS group, the improvements in EIS, KHS, MMSE, and FIM were significantly different in the VPS group after shunt (p < 0.05). Conclusion: Compared with LPS, VPS in the treatment for chronic hydrocephalus after aSAH had greater therapeutic efficacy, as indicated by improved radiological outcomes, improved shunt successful rate, improved clinical outcomes, and improved quality of life. Therefore, we believe that VPS is the preferred treatment option for chronic hydrocephalus after aSAH, while LPS should only be used as an alternative to VPS.

Mesenchymal stem/stromal cells armored by FGF21 ameliorate alcohol-induced liver injury through modulating polarization of macrophages.

BACKGROUND: Alcohol-associated liver disease (ALD) is a major health care challenge worldwide with limited therapeutic options. Although mesenchymal stem/stromal cells (MSCs) represent a newly emerging therapeutic approach to treat ALD, thus far, there have been extensive efforts to try and enhance their efficacy, including genetically engineering MSCs. FGF21, an endocrine stress-responsive hormone, has been shown to regulate energy balance, glucose, and lipid metabolism and to enhance the homing of MSCs toward injured sites. Therefore, the purpose of this study was to investigate whether MSCs that overexpress FGF21 (FGF21-MSCs) improve the therapeutic effect of MSCs in treating ALD. METHODS: Human umbilical cord-derived MSCs served as the gene delivery vehicle for the FGF21 gene. Human umbilical cord-derived MSCs were transduced with the FGF21 gene using lentiviral vectors to mediate FGF21 overexpression. We utilized both chronic Lieber-DeCarli and Gao-binge models of ethanol-induced liver injury to observe the therapeutic effect of FGF21-MSCs. Liver injury was phenotypically evaluated by performing biochemical methods, histology, and inflammatory cytokine levels. RESULTS: Compared with MSCs alone, administration of MSCs overexpressing FGF21(FGF21-MSCs) treatment significantly enhanced the therapeutic effect of ALD in mice, as indicated by the alleviation of liver injury with reduced steatosis, inflammatory infiltration, oxidative stress, and hepatic apoptosis, and the promotion of liver regeneration. Mechanistically, FGF21 could facilitate the immunomodulatory function of MSCs on macrophages by setting metabolic commitment for oxidative phosphorylation, which enables macrophages to exhibit anti-inflammatory inclination. CONCLUSIONS: Our data elucidate that MSC modification by FGF21 could enhance their therapeutic effect in ALD and may help in the exploration of effective MSCs-based cell therapies for the treatment of ALD.

Chimeric antigen receptor-modified macrophages ameliorate liver fibrosis in preclinical models.

BACKGROUND & AIMS: Treatments directly targeting fibrosis remain limited. Given the unique intrinsic features of macrophages and their capacity to engraft in the liver, we genetically engineered bone marrow-derived macrophages with a chimeric antigen receptor (CAR) to direct their phagocytic activity against hepatic stellate cells (HSCs) in multiple mouse models. This study aimed to demonstrate the therapeutic efficacy of CAR macrophages (CAR-Ms) in mouse models of fibrosis and cirrhosis and to elucidate the underlying mechanisms. METHODS: uPAR expression was studied in patients with fibrosis/cirrhosis and in murine models of liver fibrosis, including mice treated with carbon tetrachloride, a 5-diethoxycarbonyl-1, 4-dihydrocollidine diet, or a high-fat/cholesterol/fructose diet. The safety and efficacy of CAR-Ms were evaluated in vitro and in vivo. RESULTS: Adoptive transfer of CAR-Ms resulted in a significant reduction in liver fibrosis and the restoration of function in murine models of liver fibrosis. CAR-Ms modulated the hepatic immune microenvironment to recruit and modify the activation of endogenous immune cells to drive fibrosis regression. These CAR-Ms were able to recruit and present antigens to T cells and mount specific antifibrotic T-cell responses to reduce fibroblasts and liver fibrosis in mice. CONCLUSION: Collectively, our findings demonstrate the potential of using macrophages as a platform for CAR technology to provide an effective treatment option for liver fibrosis. CAR-Ms might be developed for treatment of patients with liver fibrosis. IMPACT AND IMPLICATIONS: Liver fibrosis is an incurable condition that afflicts millions of people globally. Despite the clear clinical need, therapies for liver fibrosis are limited. Our findings provide the first preclinical evidence that chimeric antigen receptor (CAR)-macrophages (CAR-Ms) targeting uPAR can attenuate liver fibrosis and cirrhosis. We show that macrophages expressing this uPAR CAR exert a direct antifibrotic effect and elicit a specific T-cell response that augments the immune response against liver fibrosis. These findings demonstrate the potential of using CAR-Ms as an effective cell-based therapy for the treatment of liver fibrosis.

SOD2 promotes the immunosuppressive function of mesenchymal stem cells at the expense of adipocyte differentiation.

The potent immunomodulatory function of mesenchymal stem/stromal cells (MSCs) elicited by proinflammatory cytokines IFN-γ and TNF-α (IT) is critical to resolve inflammation and promote tissue repair. However, little is known about how the immunomodulatory capability of MSCs is related to their differentiation competency in the inflammatory microenvironment. In this study, we demonstrate that the adipocyte differentiation and immunomodulatory function of human adipose tissue-derived MSCs (MSC(AD)s) are mutually exclusive. Mitochondrial reactive oxygen species (mtROS), which promote adipocyte differentiation, were decreased in MSC(AD)s due to IT-induced upregulation of superoxide dismutase 2 (SOD2). Furthermore, knockdown of SOD2 led to enhanced adipogenic differentiation but reduced immunosuppression capability of MSC(AD)s. Interestingly, the adipogenic differentiation was associated with increased mitochondrial biogenesis and upregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A/PGC-1α) expression. IT inhibited PGC-1α expression and decreased mitochondrial mass but promoted glycolysis in an SOD2-dependent manner. MSC(AD)s lacking SOD2 were compromised in their therapeutic efficacy in DSS-induced colitis in mice. Taken together, these findings indicate that the adipogenic differentiation and immunomodulation of MSC(AD)s may compete for resources in fulfilling the respective biosynthetic needs. Blocking of adipogenic differentiation by mitochondrial antioxidant may represent a novel strategy to enhance the immunosuppressive activity of MSCs in the inflammatory microenvironment.

Comparison of transoral vestibular robotic thyroidectomy with traditional low-collar incision thyroidectomy.

Transoral vestibular robotic thyroidectomy can really make the patient's body surface free of scar. This study aimed to compare the surgical and patient-related outcomes between the transoral vestibular robotic thyroidectomy and traditional low-collar incision thyroidectomy. The clinical data of 120 patients underwent transoral vestibular robotic thyroidectomy (TOVRT) or traditional low-collar incision thyroidectomy (TLCIT) were collected from May 2020 to October 2021. Propensity score matching analysis was used to minimize selection bias. All these patients were diagnosed with papillary thyroid carcinoma (PTC) through ultrasound-guided fine-needle aspiration prior to surgical intervention and surgical plan was tailored for each patient. An intraoperative recurrent laryngeal nerve (RLN) detection system was used in all patients, whose RLNs were identified and protected. We performed transoral vestibular robotic thyroidectomy with three intraoral incisions. Additional right axillary fold incisions were adopted occasionally to enhance fine reverse traction of tissue for radical tumor dissection. Clinical data including gender, age, tumor size, BMI, operation time, postoperative drainage volume and time, pain score, postoperative length of stay (LOS),number of lymph nodes removed, complications, and medical expense were observed and analyzed. Propensity score matching was used for 1:1 matching between the TOVRT group and the TLCIT group. All these patients accepted total thyroidectomy(or lobectomy) plus central lymph node dissection and all suffered from PTC confirmed by postoperative pathology. No conversion to open surgery happened in TOVRT group. The operative time of TOVRT group was longer than that of TLCIT group (P < 0.05). The postoperative drainage volume of TOVRT group was more than that of TLCIT group (P < 0.05). The drainage tube placement time of TOVRT group were longer than that of TLCIT group (P < 0.05). Significant differences were also found in intraoperative bleeding volume, pain score and medical expense between the two groups (P < 0.05). The incidence of perioperative common complications such as hypoparathyroidism and vocal cord paralysis in the two groups was almost identical (P > 0.05). However, there were some specific complications such as surgical area infection (one case), skin burn (one case), oral tear (two cases), and paresthesia of the lower lip and the chin (two cases) were found in TOVRT group. Obviously, the postoperative cosmetic effect of the TOVRT group was better than TLCIT group (P < 0.05). TOVRT is safe and feasible for low to moderate-risk PTC patients and is a potential alternative for patients who require no scar on their neck. Patients accepted TOVRT can get more satisfaction and have less psychologic injury caused by surgery.

Drug-repurposing by virtual and experimental screening of PFKFB3 inhibitors for pancreatic cancer therapy.

Pancreatic cancer (PC) is the most frequently occurring cancer, with few effective treatments and a 5-year survival rate of only about 11%. It is characterized by stiff interstitium and pressure on blood vessels, leading to an increased glycolytic metabolism. PFKFB3 plays an important role in glycolysis, and its products (fructose-2,6-bisphosphate), which are allosteric PFK1 activators, limit the glycolytic rate. In this study, 14 PFKFB3 inhibitors were obtained by virtually screening the FDA-approved compound library. Subsequently, the in-vitro investigations confirmed that Lomitapide and Cabozantinib S-malate exhibit the excellent potential to inhibit PFKFB3. The combined administration of Lomitapide and Gemcitabine at a certain molar ratio indicated an enhanced anti-tumor effect in Orthotopic Pancreatic Cancer (OPC) models. This investigation provides a new treatment strategy for PC therapy.

Decreased expression of TXNIP is associated with poor prognosis and immune infiltration in kidney renal clear cell carcinoma.

The most prevalent and insidious type of kidney cancer is kidney clear cell carcinoma (KIRC). Thioredoxin-interacting protein (TXNIP) encodes a thioredoxin-binding protein involved in cellular energy metabolism, redox homeostasis, apoptosis induction and inflammatory responses. However, the relationship between TXNIP, immune infiltration and its prognostic value in KIRC remains unclear. Thus, the present study evaluated the potential for TXNIP as a prognostic marker in patients with KIRC. Data from The Cancer Genome Atlas were used to assess relative mRNA expression levels of TXNIP in different types of cancer. The protein expression levels of TXNIP were evaluated using the Human Protein Atlas. Enrichment analysis of genes co-expressed with TXNIP was performed to assess relevant biological processes that TXNIP may be involved in. CIBERSORT was used to predict the infiltration of 21 tumor-infiltrating immune cells (TIICs). Univariate and multivariate Cox regression analyses were used to assess the relationship between TXNIP expression and prognosis. Single-cell RNA-sequencing datasets were used to evaluate the mRNA expression levels of TXNIP in certain immune cells in KIRC. The CellMiner database was used to analyze the relationship between TXNIP mRNA expression and drug sensitivity in KIRC. The results from the present study demonstrated that TXNIP expression was significantly decreased in KIRC tissue compared with that in normal tissue, as confirmed by western blotting and reverse transcription-quantitative PCR. In addition, downregulated TXNIP expression was significantly associated with poor prognosis, a high histological grade and an advanced stage. The Cell Counting Kit-8 assay demonstrated that TXNIP overexpression significantly suppressed tumor cell proliferation. Univariate and multivariate Cox regression analyses indicated that TXNIP served as a separate prognostic factor in KIRC. Moreover, TXNIP expression was significantly correlated with the accumulation of several TIICs and its overexpression significantly downregulated the mRNA expression levels of CD25 and cytotoxic T-lymphocyte-associated protein 4, immune cell surface markers in CD4+ T lymphocytes. In conclusion, TXNIP may be used as a possible biomarker to assess unfavorable prognostic outcomes and identify immunotherapy targets in KIRC.

Comparison of two minimally invasive surgical approaches for hypertensive intracerebral hemorrhage: a study based on postoperative intracranial pressure parameters.

BACKGROUND: Increased intracranial pressure (ICP) in patients with hypertensive intracerebral hemorrhage (HICH) has been associated with poor prognosis. The transsylvian insular approach (TIA) and the transcortical (TCA) approach are applied for patients with HICH. We aimed to compare the postoperative ICP parameters of TIA and TCA to identify which procedure yields better short-term outcomes in patients with basal ganglia hematoma volumes ranging from 30 to 50 mL. METHODS: Eighty patients with basal ganglia hematomas 30-50 mL were enrolled in this study. Patients were implanted with ICP probes and divided into TIA and TCA groups according to the procedure. The ICP values were continuously recorded for five days at four-hour intervals. Short-term outcomes were evaluated using the length of hospitalization and postoperative consciousness recovery time. RESULTS: No statistically significant differences were found in age, sex, GCS score at admission, hematoma volume, and hematoma clearance rate (p > 0.05). The results showed that postoperative initial ICP, ICP on the first postoperative day, mean ICP, DICP20 mmHg × 4 h, postoperative consciousness recovery time, the length of hospitalization, mannitol utilization rate and the mannitol dosage were lower in the TIA group than in the TCA group (p < 0.05). Postoperative consciousness recovery time was positively correlated with ICP on the first postoperative day, and the length of hospitalization was positively correlated with mean ICP. CONCLUSIONS: TIA is more effective than TCA in improving the short-term outcomes of patients with basal ganglia hematoma volumes ranging from 30 to 50 mL according to comparisons of postoperative ICP parameters.

The Identification of Gamma-Glutamyl Hydrolase in Uterine Corpus Endometrial Carcinoma: a Predictive Model and Machine Learning.

BACKGROUND: Poor neoplastic differentiation contributes to the rapid progression of uterine corpus endometrial carcinoma (UCEC). Thus, it is essential to identify candidate genes, clarifying the carcinogenesis and progression of UCEC. METHODS: We screened genes that affect differentiation and prognosis in UCEC. Least absolute selection and shrinkage operator (LASSO) regression, univariate Cox, and multivariate Cox proportional risk regression analyses were performed to screen out γ-glutamyl hydrolase (GGH) as the candidate gene. The clinical value of GGH on prognosis was evaluated. The relationship between GGH and immune infiltration was assessed by CIBERSORT, EPIC, ssGSEA, unsupervised clustering and immunohistochemistry (IHC). Additionally, we investigated the effect of GGH knockdown in vitro. RESULTS: Among the GGH, CDKN2A, and SIX1 genes, the impact of GGH was predominant on immune infiltration in UCEC. A nomogram containing GGH and other clinical features showed good predictive performance via curve analysis (DCA). In the functional analysis, GGH affected differentiation, tumour proliferation, and immune regulation. The immunosuppressive components were enriched in the GGH-high group, with poor immunotherapy efficacy. The study suggests that GGH may influence the progression of UCEC by regulating the glycolytic process. CONCLUSIONS: GGH is closely associated with various immune cell infiltrations. Our study demonstrates the prognostic role of GGH in carcinogenesis in UCEC.

The outstanding diagnostic value of DKI in multimodal magnetic resonance imaging for benign and malignant breast tumors: A diagnostic accuracy study.

To explore the value of applying different magnetic resonance imaging MRI sequences in the differential diagnosis of benign and malignant breast tumors. Routine breast magnetic resonance scans (T1-weighted image, T1WI; T2-weighted image, T2WI), dynamically enhanced scans, diffusion-weighted Imaging, and diffusion kurtosis imaging (DKI) scans were performed on 63 female patients with breast-occupying lesions. The benign and malignant lesions were confirmed by biopsy, excision-histopathology reports. There are 70 lesions, of which 46 are benign and 24 are malignant. Analyze the primary conditions, such as the shape, size, and boundary of the lesion, and determine the apparent diffusion coefficient (ADC), mean kurtosis (MK), and mean diffusion (MD) values. The receiver operating characteristic curve was used to evaluate the value and difference in differentiating benign and malignant lesions. In this study, the results of the 2 testers both showed that the MK of malignant lesions was significantly higher than that of benign lesions (P < .001), and the MD of benign lesions was higher than that of malignant lesions (P < .05). The ADC of benign lesions was higher than that of malignant lesions (P < .05). For MK, the area under the curve of the 2 testers was 0.855/0.869, respectively. When the best cutoff value of MK for tester 1 was 0.515, the sensitivity and specificity of MK for diagnosing malignant tumors were 83.3%/87.0%, respectively. For the 2 testers MD, and ADC, the area under the curve was < 0.5, and the diagnostic value was low. The MK value obtained by DKI has a specific value in the differential diagnosis of benign and malignant breast lesions. DKI is helpful in the identification of benign and malignant breast tumors. The diagnostic value is outstanding, and its importance to the changes in the microstructure of the organization needs to be further explored.

Application of radiomics based on chest CT-enhanced dual-phase imaging in the immunotherapy of non-small cell lung cancer.

OBJECTIVE: To explore the value of applying computed tomography (CT) radiomics based on different CT-enhanced phases to determine the immunotherapeutic efficacy of non-small cell lung cancer (NSCLC). METHODS: 106 patients with NSCLC who underwent immunotherapy are randomly divided into training (74) and validation (32) groups. CT-enhanced arterial and venous phase images of patients before treatment are collected. Region-of-interest (ROI) is segmented on the CT-enhanced images, and the radiomic features are extracted. One-way analysis of variance and least absolute shrinkage and selection operator (LASSO) are used to screen the optimal radiomics features and analyze the association between radiomics features and immunotherapy efficacy. The area under receiver-operated characteristic curves (AUC) along with the sensitivity and specificity are computed to evaluate diagnostic effectiveness. RESULTS: LASSO regression analysis screens and selects 6 and 8 optimal features in the arterial and venous phases images, respectively. Applying to the training group, AUCs based on CT-enhanced arterial and venous phase images are 0.867 (95% CI:0.82-0.94) and 0.880 (95% CI:0.86-0.91) with the sensitivities of 73.91% and 76.19%, and specificities of 66.67% and 72.19%, respectively, while in validation group, AUCs of the arterial and venous phase images are 0.732 (95% CI:0.71-0.78) and 0.832 (95% CI:0.78-0.91) with sensitivities of 75.00% and 76.00%, and specificities of 73.07% and 75.00%, respectively. There are no significant differences between AUC values computed from arterial phases and venous phases images in both training and validation groups (P < 0.05). CONCLUSION: The optimally selected radiomics features computed from CT-enhanced different-phase images can provide new imaging marks to evaluate efficacy of the targeted therapy in NSCLC with a high diagnostic value.

Mesenchymal stromal/stem cells and their extracellular vesicles in liver diseases: insights on their immunomodulatory roles and clinical applications.

Liver disease is a leading cause of mortality and morbidity that is rising globally. Liver dysfunctions are classified into acute and chronic diseases. Various insults, including viral infections, alcohol or drug abuse, and metabolic overload, may cause chronic inflammation and fibrosis, leading to irreversible liver dysfunction. Up to now, liver transplantation could be the last resort for patients with end-stage liver disease. However, liver transplantation still faces unavoidable difficulties. Mesenchymal stromal/stem cells (MSCs) with their broad ranging anti-inflammatory and immunomodulatory properties can be effectively used for treating liver diseases but without the limitation that are associated with liver transplantation. In this review, we summarize and discuss recent advances in the characteristics of MSCs and the potential action mechanisms of MSCs-based cell therapies for liver diseases. We also draw attention to strategies to potentiate the therapeutic properties of MSCs through pre-treatments or gene modifications. Finally, we discuss progress toward clinical application of MSCs or their extracellular vesicles in liver diseases.

High-performance flower-like and biocompatible nickel-coated Fe3O4@SiO2 magnetic nanoparticles decorated on a graphene electrocatalyst for the oxygen evolution reaction.

The electrocatalytic oxygen evolution reaction (OER) plays a crucial role in renewable clean energy conversion technologies and has developed into an important direction in the field of advanced energy, becoming the focus of basic research and industrial development. Herein, we report the synthesis and application of flower-like nickel-coated Fe3O4@SiO2 magnetic nanoparticles decorated on a graphene electrocatalyst for the OER that exhibit high efficiency and robust durability. The catalysts were optimized using a rotating ring-disk electrode to test their oxygen evolution properties in 1.0 M KOH solution. Importantly, owing to the high specific surface area and conductivity of C3N4 and graphene, the as-synthesized Fe3O4@SiO2@NiO/graphene/C3N4 exhibits a small Tafel slope of 40.46 mV dec-1, low overpotential of 288 mV at 10 mA cm-2, and robust OER durability within a prolonged test period of 100 h. The cytotoxicity of Fe3O4@SiO2, Fe3O4@SiO2@NiO, and Fe3O4@SiO2@NiO/graphene/C3N4 was evaluated in HeLa and MC3T3-E1 cells, demonstrating that they are efficient and biocompatible catalysts for the OER. Owing to its excellent electrocatalytic efficiency and eco-friendliness, Fe3O4@SiO2@NiO/graphene/C3N4 has considerable potential as a new multifunctional composite for large-scale applications in catalysis, biology, medicine, and high-efficiency hydrogen production.

Colchicine inhibits the proliferation and promotes the apoptosis of papillary thyroid carcinoma cells likely due to the inhibitory effect on HDAC1.

Although the prognosis for papillary thyroid carcinoma (PTC) is generally good, a certain proportion of patients show recurrent or advanced disease, indicating the need for further development of targeted medications. The purpose of this study was to explore the interventional effects of colchicine on PTC and the potential mechanisms or targets. We obtained PTC-related targets from the database and colchicine targets by predicting them. We screened the common targets of colchicine and the PTC-related target histone deacetylase 1 (HDAC1) and verified through molecular docking that colchicine has a good affinity for HDAC1, i.e., colchicine may act on PTC by affecting HDAC1. We then used CCK-8, colony formation, mitochondrial membrane potential and apoptosis assays to confirm that colchicine could inhibit the proliferation and promote the apoptosis of PTC cells and verified by RT‒qPCR, Western blot, and cellular immunofluorescence assays that colchicine could inhibit the expression of HDAC1 in PTC cells. The cytotoxicity and inhibitory effect of colchicine on HDAC1 in PTC cells was stronger than that in normal thyroid cells. We then applied an HDAC1 inhibitor, pyroxamide, to verify that inhibition of HDAC1 inhibits proliferation and promotes apoptosis in PTC cells. Therefore, we conclude that colchicine can inhibit the proliferation and promote the apoptosis of PTC cells likely due to its inhibitory effect on HDAC1. This finding implies that colchicine may be helpful for therapeutic intervention in PTC and that HDAC1 may be a promising clinical therapeutic target.