Development of a New Positron Emission Tomography Imaging Radioligand Targeting RIPK1 in the Brain and Characterization in Alzheimer's Disease.

Targeting receptor-interacting protein kinase 1 (RIPK1) has emerged as a promising therapeutic stratagem for neurodegenerative disorders, particularly Alzheimer's disease (AD). A positron emission tomography (PET) probe enabling brain RIPK1 imaging can provide a powerful tool to unveil the neuropathology associated with RIPK1. Herein, the development of a new PET radioligand, [11C]CNY-10 is reported, which may enable brain RIPK1 imaging. [11C]CNY-10 is radiosynthesized with a high radiochemical yield (41.8%) and molar activity (305 GBq/µmol). [11C]CNY-10 is characterized by PET imaging in rodents and a non-human primate, demonstrating good brain penetration, binding specificity, and a suitable clearance kinetic profile. It is performed autoradiography of [11C]CNY-10 in human AD and healthy control postmortem brain tissues, which shows strong radiosignal in AD brains higher than healthy controls. Subsequently, it is conducted further characterization of RIPK1 in AD using [11C]CNY-10-based PET studies in combination with immunohistochemistry leveraging the 5xFAD mouse model. It is found that AD mice revealed RIPK1 brain signal significantly higher than WT control mice and that RIPK1 is closely related to amyloid plaques in the brain. The studies enable further translational studies of [11C]CNY-10 for AD and potentially other RIPK1-related human studies.

FDA Approval Summary: Repotrectinib for locally advanced or metastatic ROS1-positive non-small cell lung cancer.

On November 15, 2023, the U.S. Food and Drug Administration (FDA) granted traditional approval to repotrectinib (Augtyro®, Bristol Myers Squibb Corporation), for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). The approval was based on TRIDENT-1, a single arm trial with multiple cohorts of patients with ROS1 fusion-positive (hereafter "ROS1-positive") NSCLC, (NCT03093116), who were either treatment naïve or had received prior ROS1 TKI and/or platinum-based chemotherapy. The primary efficacy outcome measure is objective response rate (ORR) assessed by blinded independent central review (BICR) using response evaluation criteria in solid tumors (RECIST) version 1.1. ORR was assessed in 71 patients who were ROS1 TKI naïve and 56 patients who had received a prior ROS1 TKI. Among 71 patients who were ROS1 TKI naïve, the ORR was 79% (95% CI 68, 88); median duration of response was 34.1 months (95% CI 26, NE). In patients who had received a prior ROS1 TKI and no prior chemotherapy, the ORR was 38% (95% CI 25, 52). The median duration of response was 14.8 months (95% CI 7.6, NE) BICR-assessed responses were observed in CNS metastases in patients in both cohorts, and in patients who developed resistance mutations following prior TKI therapy. The most common (> 20%) adverse reactions were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness. A unique feature of this ROS1 TKI approval is the inclusion of robust evidence of efficacy in patients with ROS1-positive NSCLC who had progressed on prior ROS1 TKIs.

Strain Effect on Dielectricity of Elastic Thermoplastic Polyurethanes.

Dielectric elastomers, such as thermoplastic polyurethanes (TPUs), are widely used as the dielectric layer, encapsulation layer, and substrate of flexible and stretchable devices. To construct capacitors and actuators that work stably upon deformation, it has become urgent to investigate the evolution of dielectricity under stress and strain. However, the lack of effective methods for estimating the dielectric constant of elastomers under strain poses a big challenge. This study reports a device for the in situ measurement of the dielectric constant of TPU under strain. It is found that upon stretching TPU to a strain of 400%, its dielectric constant decreases from 8.02 ± 0.01 to 2.88 ± 0.25 (at 1 MHz). In addition, combined Fourier-transform infrared spectroscopy, the X-ray scattering technique, and atomic force microscopy were utilized to characterize the evolution of the microstructure under strain. The investigation under tensile strain reveals a decreased density and average size of polarized hard domains, along with a tendency of the molecular chains to align in parallel with the tensile stress. The evolution of the microstructures results in a reduction in the measured dielectric constant in TPU.

Advances in Flexible Magnetosensitive Materials and Devices for Wearable Electronics.

Emerging fields, such as wearable electronics, digital healthcare, the Internet of Things, and humanoid robots, highlight the need for flexible devices capable of recording signals on curved surfaces and soft objects. In particular, flexible magnetosensitive devices garner significant attention owing to their ability to combine the advantages of flexible electronics and magnetoelectronic devices, such as reshaping capability, conformability, contactless sensing, and navigation capability. Several key challenges must be addressed to develop well-functional flexible magnetic devices. These include determining how to make magnetic materials flexible and even elastic, understanding how the physical properties of magnetic films change under external strain and stress, and designing and constructing flexible magnetosensitive devices. In recent years, significant progress is made in addressing these challenges. This study aims to provide a timely and comprehensive overview of the most recent developments in flexible magnetosensitive devices. This includes discussions on the fabrications and mechanical regulations of flexible magnetic materials, the principles and performances of flexible magnetic sensors, and their applications for wearable electronics. In addition, future development trends and challenges in this field are discussed.

Evaluating diagnostic significance: The utilization of elastography and contrast-enhanced ultrasound for differential diagnosis in breast lesions.

OBJECTIVE: The primary aim of this study is to assess the diagnostic efficacy of elastography and contrast-enhanced ultrasound (CEUS) in the identification of breast lesions subsequent to the optimization and correction of the BI-RADS category 4 classification obtained through conventional ultrasound. The objective is to augment both the specificity and accuracy of breast lesion diagnosis, thereby establishing a reliable framework for reducing unnecessary biopsies in clinical settings. METHODS: A cohort comprising 50 cases of breast lesions classified under BI-RADS category 4 was collected during the period from November 2022 and November 2023. These cases were examined utilizing strain elastography (SE), shear wave elastography (SWE), and CEUS. Novel scoring methodologies for ultrasonic elastography (UE) and CEUS were formulated for this investigation. Subsequently, the developed UE and CEUS scoring systems were used to refine and optimize the conventional BI-RADS classification, either in isolation or in conjunction. Based on the revised classification, the benign group was classified as category 3 and the suspected malignant group was classified as category 4a and above, with pathological results serving as the definitive reference standard. The diagnostic efficacy of the optimized UE and CEUS, both independently and in combination, was meticulously scrutinized and compared using receiver operating characteristic (ROC) curve analysis, with pathological findings as the reference standard. RESULTS: Within the study group, malignancy manifested in 11 cases. Prior to the implementation of the optimization criteria, 78% (39 out of 50) of patients underwent biopsies deemed unnecessary. Following the application of optimization criteria, specifically a threshold of≥8.5 points for the UE scoring method and≥6.5 points for the CEUS scoring method, the incidence of unnecessary biopsies diminished significantly. Reduction rates were observed at 53.8% (21 out of 39) with the UE protocol, 56.4% (22 out of 39) with the CEUS protocol, and 89.7% (35 out of 39) with the combined UE and CEUS optimization protocols. CONCLUSION: The diagnostic efficacy of conventional ultrasound BI-RADS category 4 classification for breast lesions is enhanced following optimized correction using UE and CEUS, either independently or in conjunction. The application of the combined protocol demonstrates a notable reduction in the incidence of unnecessary biopsies.

Elevated serum 25-hydroxyvitamin D: a potential indicator of remission in Takayasu arteritis patients with normal ESR and CRP levels.

OBJECTIVE: The goal of the present study was to investigate the correlation between serum 25-hydroxyvitamin D [25(OH)D] levels and disease remission in Takayasu arteritis (TAK) patients. METHODS: This retrospective study included 59 patients in the study group and 80 patients in the validation cohort with TAK. After 6 months of therapy, patients were re-evaluated, and serum 25(OH)D levels were compared before and after treatment. Correlations between changes in 25(OH)D levels and changes in disease activity scores (NIH, ITAS2010, ITAS.A) were analyzed. Additionally, a predictive cut-off value for disease remission was determined. RESULTS: After 6 months of therapy, serum 25(OH)D levels in TAK patients significantly increased compared to baseline [(18.33 ± 7.25)µg/L vs (11.77 ± 4.14) µg/L] (P < 0.001). Positive correlations were observed between the increasing changes in the 25(OH)D level and the decreasing changes in the reduced NIH, ITAS2010, and ITAS.A scores (r = 0.455, P < 0.001; r = 0.495, P < 0.001; and r = 0.352 P = 0.006, respectively). A change of 8.45 µg/L in 25(OH)D level was identified as the predictive cut-off value for TAK remission (sensitivity 54.1%, specificity 90.9%, area under the curve = 0.741). Similarly for patients with normal baseline ESR, sensitivity is 68.0%, specificity is 92.3%, and area under the curve is 0.831, and for patients with normal baseline CRP, sensitivity is 58.3%, specificity is 90.0%, and area under the curve is 0.748. Validation in an additional 80 patients demonstrated a higher remission rate in those with a 25(OH)D level change > 8.45 µg/L. CONCLUSION: Serum 25(OH)D levels significantly increased after treatment in TAK patients, and an increase of ≥ 8.45 µg/L was predictive of disease remission, especially in individuals with normal baseline ESR and/or CRP levels. Key Points • Following treatment, there was a significant increase in serum 25(OH)D levels among TAK patients. • The elevated changes in 25(OH)D levels before and after treatment demonstrated a positive correlation with the reduction in disease activity scores. • In patients with TAK before and after treatment, an elevation in serum 25(OH)D levels exceeding 8.45 µg/L serves as an indicator for disease remission, particularly prominent in individuals with normal baseline ESR and/or CRP levels.

Coronary artery calcification in Takayasu's arteritis: clinical characteristics and risk factors.

OBJECTIVES: Coronary artery calcification (CAC) is frequently observed in Takayasu's arteritis (TAK). Our objective is to calculate the prevalence and severity of CAC in TAK, while evaluating the influence of traditional cardiovascular risk factors, glucocorticoid exposure, and disease activity on CAC. METHODS: This retrospective study involved 155 TAK patients. We measured the Agatston score by coronary computed tomography angiography (CCTA) and categorised all patients into groups with or without CAC (41 vs. 114) to compare clinical characteristics and ancillary findings between the two groups. RESULTS: Among the TAK patients, a total of 41 TAK patients (26.45%) exhibited CAC. Age of onset, disease duration, history of hypertension, history of hyperlipidaemia, Numano V and glucocorticoid use emerged as the independent risk factors for developing CAC in TAK (OR [95% CI] 1.084[1.028-1.142], p=0.003; 1.005 [1.001-1.010], p=0.020; 4.792 [1.713-13.411], p=0.003; 4.199 [1.087-16.219], p=0.037; 3.287 [1.070-10.100], p=0.038; 3.558[1.269-9.977], p=0.016). Nonetheless, CAC was not associated with disease activity. Moreover, the extent of calcification score in TAK showed a positive correlation with the number of traditional cardiovascular risk factors. CONCLUSIONS: We recommend CCTA screening for Numano V classified TAK patients. Glucocorticoid usage significantly escalates the risk of CAC. Therefore, in cases of effectively controlled disease, the inclusion of immunosuppressants aimed at reducing glucocorticoid dosage is advisable.

Clinical features and management of germline CEBPA-mutated carriers.

Familial acute myeloid leukemia (AML) pedigrees with germline CCAAT/enhancer-binding protein-α (CEBPA) mutation have been rarely reported due to insufficient knowledge of their clinical features. Here, we report two Chinese families with multiple AML cases carrying germline CEBPA mutations, one of which had 11 cases spanning four consecutive generations. Additionally, we collected clinical data of 57 AML patients from 22 families with germline CEBPA mutations, with 58.3% of them harboring double CEBPA mutations. The first mutation frequently occurred at the N-terminal of CEBP/α (78.6%), resulting in an exclusive expression of p30 of CEBPA (CEBPAp30). The second mutation was mostly found at the C-terminal of CEBP/α (CEBPAothers). Germline CEBPAp30 carriers had higher incidences of AML (80.36% vs. 42.86%) and earlier onset of AML (18 vs. 38.5 years old) compared to germline CEBPAothers carriers. Despite the high rates of relapse, most familial AML cases exhibited favorable overall survival (OS), with germline CEBPAp30 carriers having better survival outcomes (>25 years vs. 11 years for CEBPAothers carriers). Among the 27 healthy germline CEBPA-mutated carriers, we detected a pre-leukemia clone harboring a pathogenic IDH2 variant (R140Q)in one individual. These findings should aid in the genetic counseling and management of AML patients and healthy carriers with germline CEBPA mutations.

Decreased IL-4 is the risk factor of depression in patients with Takayasu arteritis.

Objective: Depression is a common complication in Takayasu arteritis (TA). Disorders of the immune system play an important role in both diseases. This study aimed to clarify the feature of cytokines in TA patients with depression. Methods: In this cross-sectional study, serum cytokines were tested in 40 TA patients and 11 healthy controls using the Bio-Plex Magpix System (Bio-Rad®). The state of depression was measured by the Zung Self-Rating Depression Scale (SDS) in TA patients. Logistic regression analysis was performed to find the risk factors of depression in patients with TA. Results: TA patients with depression had higher ESR, hsCRP, NIH, and ITAS.A than patients without depression (16.00 [10.00, 58.50]mm/H vs. 7.50 [4.50, 17.75]mm/H, p = 0.013; 7.60 [2.32, 46.52]mg/L vs. 0.71 [0.32, 4.37]mg/L, p = 0.001; 2.00 [2.00, 3.00] vs. 1.00 [0.00, 2.00], p = 0.007; 7.00 [4.00, 9.50] vs. 1.50 [0.00, 5.75], p = 0.012, respectively). Additionally, the lower age of onset and levels of IL-4, IL-13, eotaxin, and IP-10 were observed in the depressed group compared with the non-depressed (23.50 [19.25, 32.50]pg./ml vs. 37.00 [23.25, 42.50]pg./ml, p = 0.017; 2.80 [2.17, 3.18]pg./ml vs. 3.51 [3.22, 4.66]pg./ml, p < 0.001; 0.66 [0.60, 1.12]pg./ml vs. 1.04 [0.82, 1.25]pg./ml, p = 0.008; 46.48 [37.06, 61.75]pg./ml vs. 69.14 [59.30, 92.80]pg./ml, p = 0.001; 184.50 [138.23, 257.25]pg./ml vs. 322.32 [241.98, 412.60]pg./ml, p = 0.005, respectively). The lower level of IL-4 and age of onset were the independent risk factors for depression in TA patients (OR [95% CI] 0.124 [0.018, 0.827], p = 0.031; 0.870 [0.765, 0.990], p = 0.035, respectively). Conclusion: Our data suggested that lower cytokine levels, especially IL-4, might be involved in the development of TA patients with depression. Clinicians can probably use serum IL-4 level testing as a potential indicator of depression in TA.

Long Non-coding RNA RP11-252C15.1 is a Potential Biomarker of Prognosis and Hallmark for Leukemogenesis in Children with B-cell Precursor Acute Lymphoblastic Leukemia.

INTRODUCTION: Improved understanding of the prognostic biomarkers associated with childhood acute lymphoblastic leukemia (ALL) is needed for accurate risk group stratification. This study aimed to identify potential long-non coding RNA (lncRNA) markers and evaluate their prognostic value in children with ALL. METHODS: We selected 50 children with newly diagnosed ALL and 20 age-matched patients with idiopathic immune thrombocytopenia (controls). RNA sequencing was performed to identify differentially expressed lncRNAs between the ALL and control groups. Correlation analysis was performed to determine the relationships between candidate lncRNAs, clinical features, and the risk of leukemogenesis. RESULTS: A total of 1,019 differentially expressed lncRNAs were identified between the ALL and control groups. Reverse-transcriptase (RT-qPCR) revealed that lncRNA RP11-252C15.1 and lncRNA RP11-701P16.2 were significantly upregulated in patients with ALL. Furthermore correlation analysis showed that lncRNA RP11-252C15.1 and lncRNA RP11-701P16.2 represent potential predictors of leukemogenesis; however, only lncRNA RP11-252C15.1 was associated with clinical features and outcome in children with B-cell precursor ALL (BCP-ALL). In vitro experiments confirmed that lncRNA RP11-252C15.1 was significantly overexpressed in BCP-ALL cell lines and promoted proliferation, and repressed apoptosis in MHH-CALL-3 cells. CONCLUSION: LncRNA RP11-252C15.1 is a potential oncogene in BCP-ALL pathogenesis and a prognostic biomarker in children with BCP-ALL.

Pretargeted radiotherapy and synergistic treatment of metastatic, castration-resistant prostate cancer using cross-linked, PSMA-targeted lipoic acid nanoparticles.

Metastatic castration-resistant prostate cancer (CRPC) is a currently incurable disease associated with high mortality. Novel therapeutic approaches for CRPC are urgently needed to improve prognosis. In this study, we developed cross-linked, PSMA-targeted lipoic acid nanoparticles (cPLANPs), which can interact with transmembrane glycoprotein to accumulate inside prostate cancer cells, where they upregulate caspase-3, downregulate anti-apoptotic B-cell lymphoma-2 (BCL-2), and thereby induce apoptosis. The trans-cyclooctene (TCO) decoration on cPLANPs acts as a bioorthogonal handle allowing pretargeted single-photon emission computed tomography and radiotherapy, which revealed significantly enhanced tumor accumulation and minimal off-target toxicity in our experiments. The developed strategy showed a strong synergistic anti-cancer effect in vivo, with a tumor inhibition rate of up to 95.6% after 14 days of treatment. Our results suggest the potential of combining bioorthogonal pretargeted radiotherapy with suitable PSMA-targeted nanoparticles for the treatment of metastatic CRPC.

Prognostic significance of multiparametric flow cytometry minimal residual disease at two time points after induction in pediatric acute myeloid leukemia.

BACKGROUND: Prompt response to induction chemotherapy is a prognostic factor in pediatric acute myeloid leukemia. In this study, we aimed to evaluate the prognostic significance of multiparametric flow cytometry-minimal residual disease (MFC-MRD), assessed at the end of the first and second induction courses. METHODS: MFC-MRD was performed at the end of the first induction (TP1) in 524 patients and second induction (TP2) in 467 patients who were treated according to the modified Medical Research Council (UK) acute myeloid leukemia 15 protocol. RESULTS: Using a 0.1% cutoff level, patients with MFC-MRD at the two time points had lower event-free survival and overall survival. Only the TP2 MFC-MRD level could predict the outcome in a separate analysis of high and intermediate risks based on European LeukemiaNet risk stratification and KMT2A rearrangement. The TP2 MFC-MRD level could further differentiate the prognosis of patients into complete remission or non-complete remission based on morphological evaluation. Multivariate analysis indicated the TP2 MFC-MRD level as an independent adverse prognostic factor for event-free survival and overall survival. When comparing patients with MFC-MRD ≥ 0.1%, those who underwent hematopoietic stem cell transplant during the first complete remission had significantly higher 5-year event-free survival and overall survival and lower cumulative incidence of relapse than those who only received consolidation chemotherapy. CONCLUSIONS: The TP2 MFC-MRD level can predict the outcomes in pediatric patients with acute myeloid leukemia and help stratify post-remission treatment.

Intracellular and extracellular synergistic therapy for restoring macrophage functions via anti-CD47 antibody-conjugated bifunctional nanoparticles in atherosclerosis.

Atherosclerosis is a significant contributor to global cardiovascular disease. Reducing the formation of atherosclerotic plaque effectively can lead to a decrease in cardiovascular diseases. Therefore, controlling macrophage function is crucial. This study presents the creation of a bifunctional nanoparticle that is specific to macrophages to achieve intracellular and extracellular synergistic therapy for restoring macrophage functions. The nanoparticle is conjugated with anti-CD47 antibody to modulate extracellular CD47-SIRPα phagocytic signaling axis on the outer surface of macrophages and encapsulates the NLRP3 inhibitor (CY-09) to regulate intracellular inflammation response of macrophages. The results showed that the nanoparticles accumulate in the atherosclerotic plaque, alter macrophage phagocytosis, inhibit NLRP3 inflammasome activation, and decrease the plaque burden in Apoe-/- mice whilst ensuring safety. Examination of single-cell RNA sequencing indicates that this multifunctional nanoparticle decreases the expression of genes linked to inflammation and manages inflammatory pathways in the plaque lesion. This study proposes a synergistic therapeutic approach that utilizes a bifunctional nanoparticle, conjugated with anti-CD47, to regulate the microenvironment of plaques.

A bioorthogonal cell sorting strategy for isolation of desired cell phenotypes.

Here we describe a cost-effective and simplified cell sorting method using tetrazine bioorthogonal chemistry. We successfully isolated SKOV3 cells from complex mixtures, demonstrating efficacy in separating mouse lymphocytes expressing interferon and HeLa cells expressing virally transduced green fluorescent protein post-infection.

The evaluation of four nano-formulations loaded-Elsinochrome A on characteristics and in vitro cytotoxicity effect.

Elsinochrome A (EA) is a naturally occurring photosensitizer with potential applications in photodynamic therapy (PDT) for various malignancies. Despite its promising therapeutic properties, the poor solubility of EA hampers its effective utilization in clinical settings. To circumvent this limitation, we engineered four distinct nano-formulations: PLGA/EA nanoparticles (NPs), CMC-PLGA/EA NPs, mPEG-PCL/EA nanomicelles (NMs), and LHP-CHOL/EA nanoliposomes (NLs), all designed to enhance the solubility of EA. A comparative evaluation of these formulations, based on metrics such as particle size, Zeta potential, drug loading efficiency, and encapsulation efficiency, identified PLGA/EA NPs and mPEG-PCL/EA NMs as the most efficacious candidates. Subsequent in vitro investigations into the drug release kinetics under varying pH conditions and the impact on cell viability and apoptosis in A549 and MCF-7 cell lines were conducted. Remarkably, the maximum drug release for PLGA/EA NPs and mPEG-PCL/EA NMs was recorded at 62.5% and 70.8% in an acidic environment (pH 5.7), respectively. Upon exposure to 460 nm light, PLGA/EA NPs induced a significant reduction in A549 cell viability to 13.8% and an apoptosis rate of 93.8%, whereas mPEG-PCL/EA NMs elicited a decrease in MCF-7 cell viability to 12.8% and an apoptosis rate of 73.0%.

A facile boronophenylalanine modified polydopamine dual drug-loaded nanoparticles for enhanced anti-tumor immune response in hepatocellular carcinoma comprehensive treatment.

Hepatocellular carcinoma (HCC) has an insidious onset and high malignancy. Most patients have progressed to intermediate and advanced stages by the time of diagnosis, and the long-term efficacy of traditional treatments is not satisfactory. Immunotherapy has shown great promise in the treatment of HCC in recent years; however, the low immunogenicity and severe immunosuppressive tumor microenvironment result in a low response rate to immunotherapy in HCC patients. Therefore, it is of great significance to improve the immunogenicity of HCC and thus enhance its sensitivity to immunotherapy. Here, we prepared the boronophenylalanine-modified dual drug-loaded polydopamine nanoparticles by a facile method. This system used boronophenylalanine-modified polydopamine nanoparticles as a delivery vehicle and photothermal material for the chemotherapeutic drug doxorubicin and the immune agonist CpG oligodeoxynucleotides (CpG-ODN), with both active targeting and lysosomal escape functions. The cancer cells are rapidly killed by photothermal treatment, and then chemotherapy is used to further kill cancer cells that are inadequately treated by photothermal treatment. The combination of photothermal-chemotherapy synergistically induces the release of relevant antigens from tumor cells, thus initiating anti-tumor immunity; and then cooperates with CpG-ODN to trigger a powerful anti-tumor immune memory effect, potently and durably inhibiting HCC recurrence.

Prognostic value of serum albumin level in patients with diffuse large B cell lymphoma.

OBJECTIVE: To investigate the prognostic value of serum albumin (SA) levels before chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) after receiving chemotherapy. METHODS: This is a retrospective study, and 127 patients with DLBCL including 71 males (55.9%) and 56 females (44.1%) were included. Patients' gender, age, Ann Arbor staging, eastern cooperative oncology group (ECOG) score, treatment options, international prognostic index, response rate, overall survival (OS), and progression-free survival (PFS) were obtained for statistical analysis. RESULTS: Univariate analysis showed that SA≤34 g/L, Ann Arbor III-IV, B symptoms, ECOG≥2, and bone marrow involvement suggest a poor prognosis in patients with DLBCL. Patients with persistent SA>34 g/L had significantly longer OS than patients with persistent SA≤34 g/L (P=0.020). Multivariate analysis showed that SA≤34 g/L (HR=0.48, 95% CI=0.26-0.90, P=0.022) and R-CHOP-like treatment regimen (HR=0.43, 95% CI=0.24-0.76, P=0.004) are independent factors that could affect the prognosis of patients with DLBCL. CONCLUSION: SA can be used as an indicator of prognosis in patients with DLBCL before the first chemotherapy. DLBCL patients with SA≤34 g/L are associated with short OS and poor prognosis, which may potentially provide guidance for the clinician to pay more attention to this population before the first chemotherapy.

Right Ventricular Function in Takayasu's Arteritis Patients With Pulmonary Artery Involvement Using MRI Feature Tracking.

BACKGROUND: Pulmonary artery involvement (PAI) is not rare in Takayasu arteritis (TA). Persistently elevated pulmonary arterial pressure in TA-PAI patients leads to pulmonary hypertension (PH), and eventually cardiac death. Thus, the early detection of right ventricular dysfunction before the onset of PH is important. PURPOSE: To explore the potential of right ventricular global peak longitudinal and circumferential strain (RVGLS and RVGCS, respectively) in detecting right ventricular myocardial damage in TA-PAI patients without PH. STUDY TYPE: Retrospective. POPULATION: One hundred and six TA patients (39.6 ± 13.9 years), of whom 52 were non-PAI and 54 were PAI patients (36 without PH and 18 with PH), along with 58 sex- and age-matched healthy volunteers (HVs) (36.7 ± 13.2 years). The involved arteries were validated by aorta magnetic resonance (MR) angiography and pulmonary artery computed tomography angiography. FIELD STRENGTH/SEQUENCE: 3 T/Cine imaging sequence with a steady-state free precession readout. ASSESSMENT: Cardiac MRI-derived parameters measured by two radiologists independently were compared among HVs, and TA patients with and without PAI. In addition, these indices were further compared among HVs, and TA-PAI patients with and without PH. STATISTICAL TESTS: Student's t test, one-way ANOVA analysis, Pearson and Spearman correlation analysis, and reproducibility analysis. A P-value of <0.05 was considered statistically significant. RESULTS: Although the TA-PAI patients without PH had a similar RV ejection fraction (RVEF) with HV (P = 0.348), RVGLS (non-PH 20.6 ± 3.7% vs. HV 24.0 ± 3.1%) was significantly lower and RVGCS (non-PH 14.8 ± 3.9% vs. HV 13.0 ± 2.7%) higher. The TA-PAI patients with PH had significantly poorer RVGLS (PH 13.5 ± 3.8% vs. non-PH 20.6 ± 3.7%) and RVGCS (PH 10.9 ± 3.2% vs. non-PH 14.8 ± 3.9%) than those without PH. DATA CONCLUSION: Right ventricular dysfunction was detected in the TA-PAI patients without PH. MR-feature tracking may be an effective method for detecting early cardiac damage in the TA-PAI patients without PH. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

High-throughput sequencing reveals the change of TCR α chain CDR3 with Takayasu arteritis.

OBJECTIVE: Takayasu arteritis (TAK) is an inflammatory disease of blood vessels, and its pathogenesis is not clear at present. In this study, we explored the immunological characteristics of T cell receptor (TCR) α-chain complementarity-determining region 3 (CDR3) in patients with TAK. METHODS: Five untreated patients with TAK were collected from June 2019 to December 2019. Four healthy blood samples were matched as the control group. The blood mononuclear cells were separated, and RNA was extracted for reverse transcription to obtain complementary DNA. Then high-throughput sequencing was performed. The quality of samples was evaluated by principal component analysis. We compared the diversity and expression of TCR α-chain between TAK group and control group. R software was used for statistical analysis and drawing, and Mann-Whitney U test was used to analyze the differences between the two groups. RESULTS: The results showed that there was a significant difference in the diversity of TCR α-chain CDR3 between the two groups. Three V region genes expression significantly higher in the TAK patients than in the control group. A total of 196 VJ rearrangement genes are significantly different between the two groups, of which 149 rearrangement genes in the TAK group are lower than those in the control group, and 47 rearrangement genes in the TAK group are higher than those in the control group. CONCLUSION: Patients with TAK have a unique TCR α-chain CDR3 library. These characteristic genes may be a marker for early diagnosis and provide a new theoretical basis for treating TAK.

Erythropoietin relieves neuronal apoptosis in epilepsy rats via TGF-ß/Smad signaling pathway.

This study aimed to investigate the influence of recombinant human erythropoietin (rHuEPO) on pentylenetetrazol (PTZ)-induced neuronal apoptosis in epilepsy rats, and to explore the signaling pathways related to the action. Healthy Sprague-Dawley rats aged 8 weeks old were randomly divided into 5 groups, namely, control group, PTZ model group, PTZ + rHuEPO intervention group, PTZ + SB431542 + rHuEPO intervention group and PTZ + SB431542 (TGF-ß/Smad inhibitor) intervention group. The expressions of apoptotic proteins [tumor necrosis factor receptor 1 (TNFR1) and caspase-3] and the transforming growth factor-beta (TGF-ß)/Smad signaling pathway-related proteins [phosphorylated smad3 (p-smad3) and TGF-ß1] in the brain tissues were determined via Western blotting (WB). Epilepsy was successfully induced by PTZ in the rats. The results of the TUNEL assay showed that the intervention with rHuEPO could remarkably reduce the number of PTZ-induced apoptotic neurons in the hippocampus, while SB431542 inhibitor could attenuate the protective effect of rHuEPO against neuronal apoptosis (P<0.05). In addition, the intraperitoneal injection of 50 µg/kg rHuEPO could activate the TGF-ß/Smad signaling pathway, markedly up-regulate the expressions of TGF-ß1 and p-smad3 (P<0.05), down-regulate the expressions of apoptotic proteins TNFR1 and caspase-3 (P<0.01) and reduce neuronal apoptosis. Moreover, SB431542 was able to notably repress the protective effect of rHuEPO against neuronal apoptosis, and down-regulate the expressions of p-smad3 and TGF-ß1 (P<0.01). In conclusion, the inhibitory effect of rHuEPO on nerve cell apoptosis in epilepsy rats may be realized by activating the TGF-ß/Smad signaling pathway, thus relieving neuronal apoptosis and ameliorating the symptoms of epilepsy.