Advances of ultrasound in tumor immunotherapy.

Immunotherapy has become a revolutionary method for treating tumors, offering new hope to cancer patients worldwide. Immunotherapy strategies such as checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T) therapy, and cancer vaccines have shown significant potential in clinical trials. Despite the promising results, there are still limitations that impede the overall effectiveness of immunotherapy; the response to immunotherapy is uneven, the response rate of patients is still low, and systemic immune toxicity accompanied with tumor cell immune evasion is common. Ultrasound technology has evolved rapidly in recent years and has become a significant player in tumor immunotherapy. The introductions of high intensity focused ultrasound and ultrasound-stimulated microbubbles have opened doors for new therapeutic strategies in the fight against tumor. This paper explores the revolutionary advancements of ultrasound combined with immunotherapy in this particular field.

Persistent Cytopenia After CD19 CAR T Therapy in Relapsed/Refractory DLBCL Patients Could Be a Predictor of Efficacy and Side Effects.

Hematological toxicity is a severe adverse event (AE) in anti-CD19 chimeric antigen receptor (CAR) T cell therapy for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, the pathophysiological mechanism underlying prolonged cytopenia and the relationship between persistent cytopenia, efficacy, and AEs after anti-CD19 CAR T cell therapy are unknown. Therefore, this study explored whether persistent cytopenia after anti-CD19 CAR T cell therapy in patients with R/R DLBCL can predict therapeutic efficacy and AEs. Thirty-eight patients with R/R DLBCL were enrolled in an anti-CD19 CAR T cell therapy clinical trial. Patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide before CAR T cell therapy. The degree and duration of cytopenia, clinical response, proportion of CAR T cells, interleukin-6 (IL-6) levels, AEs, and follow-up were observed after therapy. Grades 3-4 persistent cytopenia occurred in 14 patients with R/R DLBCL, who recovered 8-18 weeks after CAR T cell infusion. These patients achieved an objective response rate (ORR) for anti-CD19 CAR T cell therapy. In patients who achieved ORR, the incidence of Grades 3-4 persistent cytopenia was higher in patients with a high tumor load than in those without a high tumor load. The mean peaks of IL-6 and anti-CD19 CAR T cells and the cytokine release syndrome grade in patients with Grades 3-4 persistent cytopenia were higher than those in patients without persistent cytopenia. Anti-CD19 CAR T cells were observed 21 and 28 days after infusion, and patients had Grades 3-4 persistent cytopenia. Progression-free and overall survival were higher in patients with Grades 3-4 persistent cytopenia than in those without cytopenia. Therefore, persistent cytopenia after anti-CD19 CAR T cell therapy in patients with R/R DLBCL can predict therapeutic efficacy and AEs, allowing clinicians to determine the efficiency of CD-19 CAR T cell therapy and the associated AEs.

Regulation of Erythroid Differentiation via the HIF1α-NFIL3-PIM1 Signaling Axis Under Hypoxia.

Aims: Erythropoiesis is controlled by several factors, including oxygen level under different circumstances. However, the role of hypoxia in erythroid differentiation and the underlying mechanisms are poorly understood. We studied the effect and mechanism of hypoxia on erythroid differentiation of K562 cells and observed the effect of hypoxia on early erythropoiesis of zebrafish. Results: Compared with normal oxygen culture, both hemin-induced erythroid differentiation of K562 cells and the early erythropoiesis of zebrafish were inhibited under hypoxic treatment conditions. Hypoxia-inducible factor 1 alpha (HIF1α) plays a major role in the response to hypoxia. Here, we obtained a stable HIF1α knockout K562 cell line using the CRISPR-Cas9 technology and further demonstrated that HIF1α knockout promoted hemin-induced erythroid differentiation of K562 cells under hypoxia. We demonstrated an HIF1-mediated induction of the nuclear factor interleukin-3 (NFIL3) regulated in K562 cells under hypoxia. Interestingly, a gradual decrease in NFIL3 expression was detected during erythroid differentiation of erythropoietin-induced CD34+ hematopoietic stem/progenitor cells (HSPCs) and hemin-induced K562 cells. Notably, erythroid differentiation was inhibited by enforced expression of NFIL3 under normoxia and was promoted by the knockdown of NFIL3 under hypoxia in hemin-treated K562 cells. In addition, a target of NFIL3, pim-1 proto-oncogene, serine/threonine kinase (PIM1), was obtained by RNA microarray after NFIL3 knockdown. PIM1 can rescue the inhibitory effect of NFIL3 on hemin-induced erythroid differentiation of K562 cells. Innovation and Conclusion: Our findings demonstrate that the HIF1α-NFIL3-PIM1 signaling axis plays an important role in erythroid differentiation under hypoxia. These results will provide useful clues for preventing the damage of acute hypoxia to erythropoiesis.

A Retrospective Study to Compare Patient Outcomes from Standard Total Knee Arthroplasty (TKA) versus Navigation-Guided Arthroplasty Using the Brainlab Software-Guided Surgical System at a Center in Hebei Province January 2021 to July 2023.

BACKGROUND This retrospective study aimed to compare patient outcomes from standard total knee arthroplasty (TKA) vs navigation-guided arthroplasty using the Brainlab software-guided surgical system at Cangzhou Hospital of Integrated TCM-WM, Hebei, Hebei Province, China from January 2021 to July 2023. MATERIAL AND METHODS A total of 239 patients who underwent total knee arthroplasty in Cangzhou Hospital of Integrated TCM-WM, Hebei from January 2021 to July 2023 were retrospectively analyzed. According to the inclusion criteria, 212 eligible patients were selected for analysis and divided into a Navigation Group (NG) (n=105) and a Traditional Group (TG) (n=107) according to surgical method used. Outcomes measured included duration of disease, operative time, intraoperative blood loss volume, postoperative length of hospital stay, and pain measured by the hospital for special surgery knee score (HSS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and forgotten joint score (FJS). RESULTS The comparison of perioperative results between the 2 groups showed that the incision length in the NG was significantly longer than that in the TG (P<0.001, 95% Cl 2.59-3.35). At 3 months after surgery, the HSS score of the NG was statistically higher than that of the TG (P=0.002, 95% Cl 3.42-4.46); the WOMAC score of the NG was lower than that of the TG (P<0.001, 95% Cl -4.41-2.87); and the FJS score of the NG was significantly higher than that of the TG (P=0.003, 95% Cl 2.39-3.67). CONCLUSIONS Compared with conventional TKA, use of the Brainlab navigation system is associated with a longer incision, more accurate implantation position of the prosthesis, faster recovery of knee joint function, and helps patients to "forget" about their knee prosthesis in the short term.

Efficacy and side effects of anti-CD19 CAR T-cell therapy in patients with relapsed/refractory gastrointestinal lymphoma.

INTRODUCTION: Although anti-CD19 chimeric antigen receptor (CAR) T cell therapy was approved as a very effective salvage strategy in relapsed/refractory (R/R) B cell lymphoma, the experience in R/R gastrointestinal (GI) lymphoma is still insufficient. METHODS: We summarized the efficacy and side effects of anti-CD19 CAR T-cell therapy in 12 patients with R/R GI lymphoma. Based on literature, the R/R GI lymphoma patients were divided into subgroups with different characteristics: Bulky/No bulky disease, Gastric/Gastrointestinal involvement, Gastrointestinal/Combined extra-gastrointestinal lesions, Ulcer/Lumps or nodules type, With/without gastrointestinal bleeding. RESULTS: The objective response rate (ORR) was 66.67% in these 12 patients. The ORR was 83.33% in no bulky disease group, 80.00% in gastric involvement group, 100.00% in ulcer type group, and 80.00% in no gastrointestinal bleeding group. The CR rate was 33.33% in these 12 patients. The CR was 50.0% in no bulky disease group, 60.00% in gastric involvement group, and 80.00% in ulcer type group. The PFS and OS rate of the 12 patients at 6 months after infusion were 54.55% and 58.33%, respectively. The overall survival (OS) at 6 months was higher in no bulky disease group. There was no difference of the OS or the progression free survival (PFS) at 6 months between the other groups. The mean peak of CAR-T cells and Cytokine Release Syndrome (CRS) grade were higher in gastrointestinal lesions group. The mean peak of IFN-γ and CRS grade were higher in gastrointestinal bleeding group. Four out of six patients in group of gastrointestinal lesions group were patient with high tumor burden. Patients with gastrointestinal involvement only were at higher risk for gastrointestinal bleeding. CONCLUSIONS: The ORR and CR of high tumor load, gastrointestinal involvement, lumps or nodules type and gastrointestinal bleeding group were lower. The CRS grade was higher in gastrointestinal lesions group and in gastrointestinal bleeding group. Patients with gastrointestinal involvement only were at higher risk for gastrointestinal bleeding.

Contrast-enhanced ultrasound with microbubbles containing sulfur hexafluoride and perfluorobutane with Kupffer phase for the detection of colorectal liver metastases.

OBJECTIVE: To compare contrast-enhanced ultrasound (CEUS) with microbubbles containing sulfur hexafluoride (SHF) and perfluorobutane (PFB) for the detection of colorectal liver metastasis (CRLM). METHODS: In this prospective study, conducted from September to November 2021, patients with colorectal cancer were consecutively recruited and underwent same-day ultrasound, SHF-CEUS, and PFB-CEUS. The reference standard was contrast-enhanced MRI and follow-up imaging. The size, depth, echogenicity, and calcification of each focal liver lesion were recorded. The number and conspicuity of CRLMs, based on washout appearance during the late phase (LP) (> 120 s)/Kupffer phase (KP), were evaluated offsite by two blinded readers. RESULTS: Overall, 230 lesions (CRLMs, n = 219; benign lesions, n = 11) in 78 patients were evaluated. Lesion conspicuity (p = 0.344) and accuracy in the detection of CRLM were comparable for SHF- and PFB-CEUS (0.877 for SHF vs. 0.770 for PFB, p = 0.087). More CRLMs ≥ 10 mm were identified by LP contrast washout in SHF-CEUS than in KP PFB-CEUS (p < 0.001). More CRLMs < 10 mm were identified by KP washout in PFB-CEUS than in LP SHF-CEUS (p < 0.001). Conspicuity was better on PFB-CEUS than on SHF-CEUS (p = 0.027). In hyperechoic lesions, lesions located deeper than 80 mm, and calcified lesions, CRLM conspicuity on PFB-CEUS was inferior to that on SHF-CEUS (p < 0.05). CONCLUSIONS: The overall accuracy of detection and conspicuity of washout in CRLMs were comparable between SHF and PFB-CEUS. PFB-CEUS has the advantage of identifying washout in small CRLMs. However, larger, hyperechogenic, deep-seated, or calcified lesions were better identified using SHF-CEUS. CLINICAL RELEVANCE STATEMENT: Accuracy of detection and conspicuity of washout in CRLMs were comparable between SHF- and PFB-CEUS. PFB-CEUS has the advantage in detecting small CRLMs, whereas SHF-CEUS is better for detecting larger, hyperechogenic, deep-seated, or calcified lesions. KEY POINTS: Contrast-enhanced ultrasound with sulfur hexafluoride in the late phase and perfluorobutane microbubbles in the Kupffer phase were comparable in terms of accuracy in the detection and conspicuity of colorectal liver metastases. Small colorectal liver metastases (< 10 mm) were more often identified in the Kupffer phase contrast-enhanced ultrasound imaging when using perfluorobutane microbubbles. Larger, hyperechogenic, deep-seated, or calcified lesions were better identified in the late phase contrast-enhanced ultrasound imaging (> 120 s) when using sulfur hexafluoride microbubbles.

Associations between liver function and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in non-demented adults: The CABLE study.

Liver function has been suggested as a possible factor in the progression of Alzheimer's disease (AD) development. However, the association between liver function and cerebrospinal fluid (CSF) levels of AD biomarkers remains unclear. In this study, we analyzed the data from 1687 adults without dementia from the Chinese Alzheimer's Biomarker and LifestylE study to investigate differences in liver function between pathological and clinical AD groups, as defined by the 2018 National Institute on Aging-Alzheimer's Association Research Framework. We also examined the linear relationship between liver function, CSF AD biomarkers, and cognition using linear regression models. Furthermore, mediation analyses were applied to explore the potential mediation effects of AD pathological biomarkers on cognition. Our findings indicated that, with AD pathological and clinical progression, the concentrations of total protein (TP), globulin (GLO), and aspartate aminotransferase/alanine transaminase (ALT) increased, while albumin/globulin (A/G), adenosine deaminase, alpha-L-fucosidase, albumin, prealbumin, ALT, and glutamate dehydrogenase (GLDH) concentrations decreased. Furthermore, we also identified significant relationships between TP (ß = -0.115, pFDR < 0.001), GLO (ß = -0.184, pFDR < 0.001), and A/G (ß = 0.182, pFDR < 0.001) and CSF ß-amyloid1-42 (Aß1-42 ) (and its related CSF AD biomarkers). Moreover, after 10 000 bootstrapped iterations, we identified a potential mechanism by which TP and GLDH may affect cognition by mediating CSF AD biomarkers, with mediation effect sizes ranging from 3.91% to 16.44%. Overall, our results suggested that abnormal liver function might be involved in the clinical and pathological progression of AD. Amyloid and tau pathologies also might partially mediate the relationship between liver function and cognition. Future research is needed to fully understand the underlying mechanisms and causality to develop an approach to AD prevention and treatment approach.

Hyperbranched polyphthalocyanine micelles with dual PTT/PDT functions for bacteria eradication under an NIR window.

A Zinc phthalocyanine-based (ZnPc-PA) polymeric micelle around 70 nm and with dual-modal PTT/PDT functions for non-antibiotic bacteria eradication was developed. It showed an excellent bacterial killing efficiency of 95.2% and 96.7% in vitro against Methicillin-resistant Staphylococcus aureus (MRSA) and its biofilm, respectively. Furthermore, the in vivo experiments proved its great potential for implant-associated infection (IAI).

Percutaneous ablation of colorectal liver metastases: a comparison between the outcomes of grayscale US guidance and Sonazoid CEUS Kupffer phase guidance using propensity score matching.

PURPOSE: To assess the utility of Sonazoid contrast-enhanced ultrasound (CEUS) for guiding percutaneous microwave ablation (MWA) for colorectal liver metastases (CRLMs). MATERIALS AND METHODS: The medical records of patients who had undergone ultrasound (US)-guided percutaneous MWA between July 2020 and June 2022, were reviewed. Propensity score matching (PSM) with a ratio of 1:1 was used to balance the potential bias between the grayscale US-guided and Sonazoid CEUS-guided groups. Local tumor progression (LTP), intrahepatic recurrence (IR), and complication rates were compared between the two groups. RESULTS: Of 252 patients enrolled, 247 achieved complete ablation, and the technical effectiveness was 98.0% (247/252). Of these 247 patients, 158 were in the grayscale US-guided group and 89 in the Sonazoid CEUS-guided group. The median follow-up period was 14.6 months. After PSM, there were no significant differences in LTP, IR, or complication rates between the two groups (p = 0.100, p = 0.511, p > 0.99, respectively). Multivariate analysis identified tumor size ≥ 3 cm (hazard ratio [HR], 7.945; 95% CI, 2.591-24.370; p < 0.001), perivascular (HR, 2.331; 95% CI, 1.068-5.087; p = 0.034), and tumor depth > 8 cm (HR, 3.194; 95% CI, 1.439-7.091; p = 0.004) as significant factors associated with LTP. For tumors with poor vision on grayscale US, Sonazoid CEUS-guided ablation achieved a better LTP rate than grayscale US-guided ablation (3.7% vs.14.8%, p = 0.032). CONCLUSION: For tumors with poor vision on grayscale US, Sonazoid CEUS guidance is recommended for better local tumor control.

Efficient removal of phosphate from aqueous media using magnetic bimetallic lanthanum­iron-modified sulfonylmethylated lignin biochar.

The use of lignin carbon as an adsorbent for the adsorption of phosphates from wastewater is a promising technology. However, most lignin carbon-based adsorbents still suffer from low adsorption efficiency and poor selectivity. Herein, a novel FeLaO3-modified sulfomethylated lignin (SL) biochar adsorbent (FLO@CSL) was prepared for phosphate removal. The development of this adsorbent took into consideration the strong affinity of lanthanum (La) and iron (Fe) (hydro) oxides for phosphate and the excellent carrier properties of lignin-based biochar. As the core of FLO@CSL, FeLaO3 active sites are highly dispersed on the surface of SL biochar. Besides, doping of Fe(III) not only imparts magnetic properties to FLO@CSL, thereby effectively improving the separation efficiency of the adsorbent, but also enhances the phosphate adsorption performance. Performance studies revealed that FLO@CSL exhibits remarkable adsorption selectivity and substantial phosphate-adsorption capacity. Notably, the maximum adsorption capacity was found to be 137.14 mg P g-1. Phosphate adsorption on the FLO@CSL surfaces proceeds via chemisorption in a single layer, and ligand exchange plays an important role in determining the adsorption behaviour. Because of its exceptional selectivity, remarkable adsorption capacity and outstanding magnetic separation efficiency, FLO@CSL is a highly promising adsorbent material for effectively treating phosphates in wastewater.

Comparison of total corneal power measurements obtained with different devices after myopic keratorefractive surgery.

AIM: To analyze the differences, agreements, and correlation among total corneal power parameters generated by different instruments after myopic keratorefractive surgery. METHODS: The prospective cross-sectional study included patients who underwent myopic keratorefractive surgery and received measurements of corneal power 3mo after surgery. Automated keratometer was used for the measurement of simulated keratometry (SimK), swept-source optical coherence tomography (SS-OCT) based biometer for total keratometry (TK), anterior segment-OCT for real keratometry (RK), and Scheimpflug keratometer for the true net power (TNP), the total corneal refractive power (TCRP) and equivalent K-readings (EKR). The differences among these parameters were analyzed, and the agreements and correlation between SimK and other total corneal power parameters were investigated. RESULTS: A total of 70 eyes of 70 patients after myopic keratorefractive surgery were included. The evaluated corneal power parameters were as follows: SimK 38.32±1.93 D, TK 37.54±2.12 D, RK 36.64±2.09 D, TNP 36.56±1.97 D, TCRP 36.70±2.01 D, and EKR 37.55±2.00 D. Pairwise comparison showed that there were significant differences (P<0.001) among all parameters except for between TK and EKR, RK and TNP, RK and TCRP (P=1.000, 1.000, 1.000, respectively). The limits of agreement between SimK and TK, RK, TNP, TCPR, and EKR were 1.08, 1.08, 1.43, 1.48, and 1.73 D, respectively. All parameters showed good correlation with SimK, and the correlation coefficients were 0.995, 0.994, 0.983, 0.982, and 0.975. CONCLUSION: Among the corneal power parameters after myopic keratorefractive surgery, the value of SimK is the largest, followed by TK and EKR, with TCRP, RK, and TNP being the smallest. The differences among the parameters may be attributable to the different calculation principles. Correct understanding and evaluation of corneal power parameters can provide a theoretical basis for taking advantage of the total corneal power to improve the accuracy of intraocular lens calculation after keratorefractive surgery.

Comparative analysis of ultrasonic elastosonography and contrast-enhanced ultrasonography in the diagnosis of benign and malignant intraocular tumors.

PURPOSE: To compare the diagnostic value of ultrasonic elastosonography (UE) and contrast-enhanced ultrasonography (CEUS) for benign and malignant intraocular tumors. METHODS: This retrospective study enrolled patients with intraocular tumors at Beijing Tongren Hospital, Capital Medical University (August 2016 to January 2020). The strain rate ratio (strain rate of tumor tissue divided by strain rate of surrounding normal tissue) was measured by UE. CEUS was performed using SonoVue® contrast agent. The performance of each method at differentiating benign from malignant intraocular tumors was evaluated by receiver operating characteristic curve analysis. RESULTS: The analysis included 147 eyes in 145 patients (45.6 ± 13.4 years-old; 66 males): 117 patients (119 eyes) with malignant tumors and 28 patients (28 eyes) with benign tumors. At an optimal cutoff of 22.67 for the strain rate ratio, UE distinguished benign from malignant tumors with a sensitivity of 86.6% and a specificity of 96.4%. CEUS showed that 117 eyes with malignant tumors had a fast-in, fast-out time-intensity curve, and only two eyes with malignant tumors had a fast-in, slow-out curve, while all 28 eyes with benign tumors had a fast-in, slow-out curve. CEUS differentiated benign from malignant tumors with a sensitivity of 98.3% and a specificity of 100%. The diagnostic results differed significantly between the two methods (P = 0.004, McNemar test). The diagnostic performances of the two tests were moderately consistent (κ = 0.657, P < 0.001). CONCLUSION: Both CEUS and UE have good diagnostic value in the differentiation of benign intraocular tumors from malignant intraocular tumors.

Efficacy and safety-related factors of BTK inhibitors as a bridge to CAR-T therapy in R/R FL.

Although anti-CD19 chimeric antigen receptor (CAR) T cell therapy has achieved satisfactory results in relapsed/refractory (R/R) follicular lymphoma (FL), patients with R/R FL and high-risk disease characteristics, previous hematopoietic stem cell transplantation, bulky disease, and progression of disease within 2 years (POD24) had a low complete response (CR). Twenty-seven patients with R/R FL, later disease stages, higher tumor burden, or higher previous treatment lines who had received Bruton tyrosine kinase (BTK) inhibitors before anti-CD19 CAR T cell therapy, or received BTK inhibitors as combination therapy, were included in this study. The clinical response and adverse events (AEs) in anti-CD19 CAR T cell therapy were observed. All patients with R/R FL who received BTK inhibitors combined with anti-CD19-CAR T cell therapy had later disease stages, higher tumor burden, and higher treatment lines than those who did not receive BTK inhibitor combination therapy. However, no difference in the clinical response was found between the two groups. The clinical response in the POD24 group was lower than that in the non-POD24 group; however, no difference in the clinical response was found between the FL and transformed FL (tFL) groups, between the follicular lymphoma international prognostic index (FLIPI) 1 1-2 and FLIPI 1 3-5 groups, and between the FLIPI 2 1-2 and FLIPI 2 3-5 groups. The mean anti-CD19 CAR T cell peak was higher in the CAR-T group with BTK inhibitor than in the CAR-T group without BTK inhibitor. Meanwhile, a higher proportion of patients in the non-POD24 group, FL group, and PR group achieved CR after 2 months. No difference in cytokine secretion was found between the CAR-T group with and without BTK inhibitors. It was higher in the non-POD24 group, FLIPI 1 3-5 group, and FLIPI 2 3-5 group. No difference in cytokine release syndrome and immune effector cell-associated neurotoxic syndrome grades was found between the CAR-T groups with or without BTK inhibitors and between the other groups. Poor prognostic factors, other than POD24, did not affect the clinical response to BTK inhibitors in combination with anti-CD19 CAR T cell therapy in patients with R/R FL. Therefore, BTK inhibitors combined with anti-CD19 CAR-T therapy may be an effective and safe approach for patients with R/R FL and high-risk factors.Trial registration: The study was registered at http://www.chictr.org.cn/index.aspx as ChiCTR-ONN-16009862 and http://www.chictr.org.cn/index.aspx as ChiCTR1800019622.

Value of the strain ratio in the differential diagnosis of intraocular tumors by elastosonography: A retrospective case-control study.

Purpose: To examine the role of the strain ratio in elastosonography for the differential diagnosis of common intraocular tumors such as choroidal melanoma, choroidal hemangioma, choroidal metastatic carcinoma, and retinoblastoma. Methods: This study included patients suffering from intraocular space-occupying lesions and who visited Beijing Tongren Eye Center of Beijing Tongren Hospital affiliated to Capital Medical University from June 2016 to March 2020. All patients underwent a physical examination, fundus examination with mydriasis, color Doppler ultrasonography, elastosonography, magnetic resonance imaging (MRI), and fundus angiography within 1 week. All patients were grouped as choroidal melanoma, choroidal metastatic carcinoma, retinoblastoma, choroidal hemangioma, and optic disk melanocytoma. A receiver operating characteristic (ROC) curve analysis was performed to assess the strain ratio for diagnosing malignant intraocular tumors. Results: A total of 155 patients (161 eyes) were recruited. The strain ratios measured were 39.59 ± 15.92 for choroidal melanoma, 36.85 ± 13.64 for choroidal metastatic carcinoma, 38.93 ± 17.27 for retinoblastoma, 13.42 ± 10.93 for choroidal hemangioma, and 3.84 ± 1.32 for optic disk melanocytoma. The strain ratios of the three malignant lesions were significantly higher than those of the two benign lesions (all P < 0.001). The area under the ROC curve was 0.95 ± 0.028. The optimal cutoff point was 22.67, with 85.7% sensitivity and 96.4% specificity. Conclusion: There were significant differences in elasticity between the malignant and benign intraocular tumors. The strain ratio using elastosonography could serve as an important auxiliary examination to distinguish between benign and malignant intraocular tumors.

Bone marrow mesenchymal stem cells derived exosomal Lnc TUG1 promotes bone fracture recovery via miR-22-5p/Anxa8 axis.

Bone fracture healing is a complex physiologic process that involves changes in the expression of several thousand genes. Long noncoding RNAs (lncRNAs) may have critical biological roles in this process. The objectives of the present study were to determine whether BMSC-derived exosomal lncTUG1 can enhance osteogenic differentiation and thereby promoting bone fracture recovery and to investigate its potential mechanisms of action. Bone marrow mesenchymal stromal cells were isolated from mice and cultured for the following experiments. After adipogenic and osteogenic differentiation induction, Oil Red O, alizarin red S, and alkaline phosphatase staining solutions were applied to confirm the formation of lipid droplets and calcium nodules. Western blotting analyses, real-time reverse transcription PCR assays, luciferase reporter were performed to confirm relative RNA and protein expressions and luciferase activities of transfected cells. RNA pull-down and RNA immunoprecipitation assays were also carried to verify the interaction between lncTUG1 and miR-22-5p. Additionally, a mouse model of closed femoral fractures was generated to evaluate the in vivo effect of increased lncTUG1 on fracture healing. BMSC-derived exosomal lncTUG1 enhanced the activity of osteoblasts. Overexpression of miR-22-5p reversed the osteopromoting effect of increased lncTUG1. The knockdown of Anxa8 reversed the osteogenic effect of miR-22-5p inhibitors, indicating an interaction between Anxa8 and miR-22-5p. Upregulation of lncTUG1 could promote the fracture recovery in vivo. In conclusion, the present study highlights the functional importance of BMSC-derived exosomal lncTUG1 in the process of bone fracture recovery.

Model and online calculator for prediction of fistula maturation based on vein dilation and age: A retrospective cohort study in a single-center.

OBJECTIVE: A model that considers the characteristics of dialysis patients may help predict successful fistula maturation. We evaluated factors associated with radiocephalic arteriovenous fistula (RCAVF) maturation at 3 months in dialysis patients with end-stage renal disease (ESRD). METHODS: A total of 184 patients who received an initial RCAVF at Beijing Haidian Hospital (Haidian Section of Peking University Third Hospital) were recruited. Fistula maturation was assessed within 3 months. Patient characteristics and preoperative vascular assessment indices were examined. Factors associated with fistula maturation were analyzed using logistic regression and least absolute shrinkage and selection operator (LASSO) binary logistic regression. Boostrapping was used for internal validation. RESULTS: The development data consisted of 184 ESRD patients receiving an initial RCAVF, 140 (76%) of whom achieved fistula maturation. The main predictors of RCAVF maturation in the final model were sex, age-adjusted vein dilation (eVD), radial artery volume (Vartery), and diastolic blood pressure. The difference of vein diameter with and without a tourniquet was significantly larger in the mature RCAVF group (3.0 ± 0.5 vs. 2.2 ± 0.5 mm). The area under receiver operating characteristic (AUROC) curve for prediction of fistula maturation was 0.77, and the Hosmer-Lemeshow statistic indicated agreement between observed and predicted values (P = 0.792). Analysis of internal validation using bootstrapping indicated the C-index was 0.75. CONCLUSION: The ratio of vein dilation and age were the major predictors of fistula maturation at 3 months in our patients. The resulting online prediction model may help in clinical decision-making for patients receiving a RCAVF.

Mechanistic studies of polyphenols reducing the trypsin inhibitory activity of ovomucoid: Structure, conformation, and interactions.

Ovomucoid (OVM) is a critical anti-nutritional factor in egg, which may reduce nutrient utilization. In this study, the effects of polyphenols on the trypsin inhibitory activity (TIA) of OVM were investigated by exploring the structural changes and interaction mechanisms. The results found that TIA decreased to 62.34% and 90.41% as epigallocatechin gallate (EGCG) and gallic acid (GA) were added individually. EGCG and GA interacted with OVM via static quenching and hydrophobic interaction. They induced a transition of OVM conformation from disorder to order. Infrared and fluorescence quenching analysis showed that the interaction between EGCG or GA and OVM was spontaneous, and hydrophobic interaction was the predominant force. The mechanism suggested that polyphenols affect the protein conformation by spontaneously binding to OVM in hydrophobic interactions, and lowering the TIA through reduced hydrophobicity. In summary, EGCG may be a promising OVM trypsin activity inactivator, which could also guarantee safety of egg products.

Construction of a ferroptosis-related signature based on seven lncRNAs for prognosis and immune landscape in clear cell renal cell carcinoma.

BACKGROUND: Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are involved in regulating tumor cell ferroptosis. However, prognostic signatures based on ferroptosis-related lncRNAs (FRLs) and their relationship to the immune microenvironment have not been comprehensively explored in clear cell renal cell carcinoma (ccRCC). METHODS: In the present study, the expression profiles of ccRCC were acquired from The Cancer Genome Atlas (TCGA) database; 459 patient specimens and 69 adjacent normal tissues were randomly separated into training or validation cohorts at a 7:3 ratio. We identified 7 FRLs that constitute a prognostic signature according to the differential analysis, correlation analysis, univariate regression, and least absolute shrinkage and selection operator (LASSO) Cox analysis. To identify the independence of risk score as a prognostic factor, univariate and multivariate regression analyses were also performed. Furthermore, CIBERSORT was conducted to analyze the immune infiltration of patients in the high-risk and low-risk groups. Subsequently, the differential expression of immune checkpoint and m6A genes was analyzed in the two risk groups. RESULTS: A 7-FRLs prognostic signature of ccRCC was developed to distinguish patients into high-risk and low-risk groups with significant survival differences. This signature has great prognostic performance, with the area under the curve (AUC) for 1, 3, and 5 years of 0.713, 0.700, 0.726 in the training set and 0.727, 0.667, and 0.736 in the testing set, respectively. Moreover, this signature was significantly associated with immune infiltration. Correlation analysis showed that risk score was positively correlated with regulatory T cells (Tregs), activated CD4 memory T cells, CD8 T cells and follicular helper T cells, whereas it was inversely correlated with monocytes and M2 macrophages. In addition, the expression of fourteen immune checkpoint genes and nine m6A-related genes varied significantly between the two risk groups. CONCLUSION: We established a novel FRLs-based prognostic signature for patients with ccRCC, containing seven lncRNAs with precise predictive performance. The FRLs prognostic signature may play a significant role in antitumor immunity and provide a promising idea for individualized targeted therapy for patients with ccRCC.