Evaluation of left ventricular blood flow kinetic energy in patients with acute myocardial infarction by 4D Flow MRI: a preliminary study.

PURPOSE: To evaluate the intracavity left ventricular (LV) blood flow kinetic energy (KE) parameters using four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) in patients with acute myocardial infarction (AMI). METHODS: Thirty AMI patients and twenty controls were examined via CMR, which included cine imaging, late gadolinium enhancement (LGE) and global heart 4D flow imaging. The KE parameters were indexed to LV end-diastolic volume (EDV) to obtain average, systolic and diastolic KE as well as the proportion of LV in-plane KE (%). These parameters were compared between the AMI patients and controls and between the two subgroups. RESULTS: Analysis of the LV blood flow KE parameters at different levels of the LV cavity and in different segments of the same level showed that the basal level had the highest blood flow KE while the apical level had the lowest in the control group. There were no significant differences in diastolic KE, systolic in-plane KE and diastolic in-plane KE between the anterior wall and posterior wall (p > 0.05), only the systolic KE had a significant difference between them (p < 0.05). Compared with those in the control group, the average (10.7 ± 3.3 µJ/mL vs. 14.7 ± 3.6 µJ/mL, p < 0.001), systolic (14.6 ± 5.1 µJ/mL vs. 18.9 ± 3.9 µJ/mL, p = 0.003) and diastolic KE (7.9 ± 2.5 µJ/mL vs. 10.6 ± 3.8 µJ/mL, p = 0.018) were significantly lower in the AMI group. The average KE in the infarct segment was lower than that in the noninfarct segment in the AMI group (49.5 ± 18.7 µJ/mL vs. 126.3 ± 50.7 µJ/mL, p < 0.001), while the proportion of systolic in-plane KE increased significantly (61.8%±11.5 vs. 42.9%±14.4, p = 0.001). CONCLUSION: The 4D Flow MRI technique can be used to quantitatively evaluate LV regional hemodynamic parameters. There were differences in the KE parameters of LV blood flow at different levels and in different segments of the same level in healthy people. In AMI patients, the average KE of the infarct segment decreased, while the proportion of systolic in-plane KE significantly increased.

Identification and Expression Analysis of the Nucleotidyl Transferase Protein (NTP) Family in Soybean (Glycine max) under Various Abiotic Stresses.

Nucleotidyl transferases (NTPs) are common transferases in eukaryotes and play a crucial role in nucleotide modifications at the 3' end of RNA. In plants, NTPs can regulate RNA stability by influencing 3' end modifications, which in turn affect plant growth, development, stress responses, and disease resistance. Although the functions of NTP family members have been extensively studied in Arabidopsis, rice, and maize, there is limited knowledge about NTP genes in soybeans. In this study, we identified 16 members of the NTP family in soybeans, including two subfamilies (G1 and G2) with distinct secondary structures, conserved motifs, and domain distributions at the protein level. Evolutionary analysis of genes in the NTP family across multiple species and gene collinearity analysis revealed a relatively conserved evolutionary pattern. Analysis of the tertiary structure of the proteins showed that NTPs have three conserved aspartic acids that bind together to form a possible active site. Tissue-specific expression analysis indicated that some NTP genes exhibit tissue-specific expression, likely due to their specific functions. Stress expression analysis showed significant differences in the expression levels of NTP genes under high salt, drought, and cold stress. Additionally, RNA-seq analysis of soybean plants subjected to salt and drought stress further confirmed the association of soybean NTP genes with abiotic stress responses. Subcellular localization experiments revealed that GmNTP2 and GmNTP14, which likely have similar functions to HESO1 and URT1, are located in the nucleus. These research findings provide a foundation for further investigations into the functions of NTP family genes in soybeans.

Effects of Transcranial Direct Current Stimulation on Graph Naming Function and Brain Connectivity in Post-Infarction Aphasia Patients: An fMRI Study.

OBJECTIVE: The study aimed to investigate the mechanisms of impairment and recovery in graph naming functions among patients with aphasia due to cerebral infarction. Specifically, the study compared immediate effects of transcranial Direct Current Stimulation (tDCS) treatment in patients at different stages post-infarction: the acute phase and the recovery period. METHODS: Twenty-eight patients were selected, consisting of 16 in the acute phase (AP) and 12 in the recovery period (RP), along with 18 healthy controls. Both patient groups underwent two weeks of tDCS treatment. Post-treatment changes in functional connectivity (FC) within language-related brain regions, as well as in graph naming abilities, were assessed in both patient groups. RESULTS: Both AP and RP groups exhibited significant improvements in graph naming ability following tDCS treatment. Compared to healthy controls, patients showed decreased functional connectivity in multiple brain regions of both hemispheres, particularly in the dominant hemisphere. Post-treatment assessments revealed significant increases in functional connectivity within the bilateral frontotemporal lobes for both AP and RP groups, and within the bilateral temporo-occipital regions for the AP group. Moreover, the RP group demonstrated decreased functional connectivity in the left temporal lobe post-treatment, which had shown increased functional connectivity pre-treatment. CONCLUSIONS: This study suggests that tDCS can effectively enhance graph naming functions in patients with post-infarction aphasia. The therapeutic effects appear to be mediated by enhancing functional connectivity within bilateral frontotemporal lobes.

Assessment of nucleus accumbens impairment in a rat model of postoperative cognitive dysfunction using diffusion tensor imaging.

BACKGROUND: Postoperative cognitive dysfunction (POCD) often occurs in elderly patients, causing depression and other symptoms. Nucleus accumbens (NAc) is involved in depression. We investigate the diffusion tensor imaging (DTI) parameters of NAc in a POCD model of depression. METHODS: Twenty-month-old male Sprague-Dawley (SD) rats were randomly divided into the POCD and Sham groups. The POCD group underwent exploratory laparotomy to establish a POCD depression model, while the Sham group underwent a sham operation. The fractional anisotropy (FA) and mean diffusivity (MD) values of the bilateral NAc, behavioural changes of forced swimming test and sucrose preference rate, and pathological changes of glial fibrillary acidic protein (GFAP) fluorescent intensity were observed at 15 days (D15 ) and 30 days (D30 ) after the operation. RESULTS: The FA value of the bilateral NAc area in the POCD group was lower than that in the Sham group at the two time periods after the operation (P < 0.05). However, the MD value at D30 was higher in the POCD group than in the Sham group (P < 0.05). The FA value in the POCD group was lower at D30 than at D15 (P < 0.05). The floating time was prolonged while the sucrose preference rate was decreased in the POCD group compared with the Sham group (P < 0.05). The floating time in the POCD group was longer at D30 than at D15 . However, the sucrose preference rate in the POCD was lower at D30 than at D15 . The GFAP fluorescent intensity in the bilateral NAc region in the POCD group was higher than in the Sham group (P < 0.05). CONCLUSION: Microstructural changes of the NAc area are associated with POCD related depression. In addition, FA and MD were demonstrated to be effective in diagnosing and monitoring postoperative depression and its severity.

Investigation of CRS-associated cytokines in CAR-T therapy with meta-GNN and pathway crosstalk.

BACKGROUND: Chimeric antigen receptor T-cell (CAR-T) therapy is a new and efficient cellular immunotherapy. The therapy shows significant efficacy, but also has serious side effects, collectively known as cytokine release syndrome (CRS). At present, some CRS-related cytokines and their roles in CAR-T therapy have been confirmed by experimental studies. However, the mechanism of CRS remains to be fully understood. METHODS: Based on big data for human protein interactions and meta-learning graph neural network, we employed known CRS-related cytokines to comprehensively investigate the CRS associated cytokines in CAR-T therapy through protein interactions. Subsequently, the clinical data for 119 patients who received CAR-T therapy were examined to validate our prediction results. Finally, we systematically explored the roles of the predicted cytokines in CRS occurrence by protein interaction network analysis, functional enrichment analysis, and pathway crosstalk analysis. RESULTS: We identified some novel cytokines that would play important roles in biological process of CRS, and investigated the biological mechanism of CRS from the perspective of functional analysis. CONCLUSIONS: 128 cytokines and related molecules had been found to be closely related to CRS in CAR-T therapy, where several important ones such as IL6, IFN-γ, TNF-α, ICAM-1, VCAM-1 and VEGFA were highlighted, which can be the key factors to predict CRS.

Ruxolitinib reduces severe CRS response by suspending CAR-T cell function instead of damaging CAR-T cells.

The therapeutic effect of CAR-T is often accompanied by sCRS, which is the main obstacle to the promotion of CAR-T therapy. The JAK1/2 inhibitor ruxolitinib has recently been confirmed as clinically effective in maintaining control over sCRS, however, its mechanism remains unclear. In this study, we firstly revealed that ruxolitinib significantly inhibited the proliferation of CAR-T cells without damaging viability, and induced an efficacy-favored differentiation phenotype. Second, ruxolitinib reduced the level of cytokine release not only from CAR-T cells, but also from other cells in the immune system. Third, the cytolytic activity of CAR-T cells was restored once the ruxolitinib was removed; however, the cytokines released from the CAR-T cells maintained an inhibited state to some degree. Finally, ruxolitinib significantly reduced the proliferation rate of CAR-T cells in vivo without affecting the therapeutic efficacy after withdrawal at the appropriate dose. We demonstrated pre-clinically that ruxolitinib interferes with both CAR-T cells and the other immune cells that play an important role in triggering sCRS reactions. This work provides useful and important scientific data for clinicians on the question of whether ruxolitinib has an effect on CAR-T cell function loss causing CAR-T treatment failure when applied in the treatment of sCRS, the answer to which is of great clinical significance.

CD20-specific chimeric antigen receptor-expressing T cells as salvage therapy in rituximab-refractory/relapsed B-cell non-Hodgkin lymphoma.

BACKGROUND AIMS: The infusion of chimeric antigen receptor (CAR) T cells that target specific tumor-associated antigens is a promising strategy that has exhibited encouraging results in clinical trials. However, few studies have focused on the effectiveness and safety of CD20 CAR T cells in rituximab-refractory/relapsed (R/R) B-cell non-Hodgkin lymphoma (B-NHL) patients, particularly those treated with rituximab for a short time. This prospective study aimed to assess the effectiveness and toxicity of CD20 CAR T cells in R/R B-NHL patients previously treated with rituximab. METHODS: The authors conducted a prospective, single-center phase I study on the effectiveness and toxicity of CD20 CAR T cells in rituximab-treated R/R B-NHL patients (no. ChiCTR2000036350). A total of 15 patients with R/R B-NHL were enrolled between November 21, 2017, and December 1, 2021. RESULTS: An overall response rate of 100% was shown in enrolled patients, with 12 (80%) achieving complete remission and three (20%) achieving partial remission for the best response. The median follow-up time was 12.4 months. Progression-free survival and overall survival were not yet reached by the data cutoff day. No patient developed grade 4 cytokine release syndrome, and only one patient had immune effector cell-associated neurotoxicity syndrome. CONCLUSIONS: All enrolled B-NHL patients who were previously R/R to rituximab achieved different degrees of clinical response with tolerable toxicities. Notably, patients who had received rituximab within 3 months had a poorer prognosis.

Anti-CD19 and anti-BCMA CAR T cell therapy followed by lenalidomide maintenance after autologous stem-cell transplantation for high-risk newly diagnosed multiple myeloma.

Few prospective studies have examined posttransplant chimeric antigen receptor (CAR) T cell infusion as candidates for front-line consolidation therapy for high-risk multiple myeloma (MM) patients. This single-arm exploratory clinical trial is the first to evaluate the safety and efficacy of sequential anti-CD19 and anti-BCMA CAR-T cell infusion, followed by lenalidomide maintenance after autologous stem cell transplantation (ASCT), in 10 high-risk newly diagnosed multiple myeloma (NDMM) patients. The treatment was generally well tolerated, with hematologic toxicities being the most common grade 3 or higher adverse events. All patients had cytokine release syndrome (CRS), which was grade 1 in 5 patients (50%) and grade 2 in 5 patients (50%). No neurotoxicity was observed after CAR-T cell infusion. The overall response rate was 100%, with the best response being 90% for a stringent complete response (sCR), and 10% for a complete response (CR). At a median follow-up of 42 (36-49) months, seven (70%) of 10 patients showed sustained minimal residual disease (MRD) negativity for more than 2 years. The median progression-free survival (PFS) and overall survival (OS) were not reached. Although the sample size was small and there was a lack of control in this single-arm study, the clinical benefits observed warrant ongoing randomized controlled trials.

Diagnostic value of spiral CT energy spectrum imaging in lymph node metastasis of colorectal cancer.

OBJECTIVES: To evaluate the value of preoperative CT energy spectrum imaging in detecting lymph node metastasis of colorectal cancer. METHODS: From September 2019 to November 2021, a retrospective study was performed for the eighty-two patients with colorectal cancer through preoperative colonoscopy or surgical pathology confirmed in our hospital. Based on the lymph node metastasis status, these cases were divided into the metastasis and non-metastasis groups. GE Revolution CT scanner was used to scan the patients with energy spectrum imaging, it measured and recorded the single-energy CT values from 40 to 140 keV and various energy spectrum parameters of lymph nodes around the lesions in the arterial and venous phases, and statistically analyze the above indices. RESULTS: In the arterial and venous phases: the single-energy CT values of 40-140 keV in the non-metastatic group were higher than those in the metastatic group (all P < 0.05); the parameter values of IC (iodine concentration), NIC (normalized iodine concentration), λ (the slope of the energy spectrum curve), and Eff-Z (effective-Z) in the non-metastatic group were higher than those in the metastatic group (all P < 0.05). Further evaluation of ROC curve showed that the higher AUC (area under curve) of the single-energy CT value of 50 keV in the arterial phase was 0.889, among the energy spectrum parameters of IC, NIC, λ, and Eff-Z, the NIC had the better diagnostic efficiency and the AUC of the NIC was 0.873, the highest AUC of the combination of NIC and λ was 0.885 when the energy spectrum parameters were combined. The higher AUC of the single-energy CT value of 60 keV in the venous phase was 0.853, among the energy spectrum parameters of IC, NIC, λ, and Eff-Z, the λ had the better diagnostic efficiency and the AUC of the λ was 0.822, the higher AUC of the combination of NIC, λ, and Eff-Z was 0.840 when the energy spectra were combined. CONCLUSIONS: Parameters of energy spectrum CT imaging can effectively evaluate whether lymph nodes have metastases, and provide favorable imaging diagnosis basis for the range and the number of lymph nodes to be cleaned during clinical operation and can evaluate the prognosis of patients. It is worthy of clinical recommendation.

Prognostic value of the SYNTAX score on myocardial injury and salvage in STEMI patients after primary percutaneous coronary intervention: a single-center retrospective observational study.

BACKGROUND: SYNTAX score (SS) was shown to positively correlate with postprocedural myocardial injury in patients after elective coronary artery intervention, but evidence about the association of SS with myocardial salvage in ST-segment elevation myocardial infarction (STEMI) patients is still needed. This study aimed to evaluate the prognostic value of SS for myocardial injury and salvage assessed by cardiac magnetic resonance (CMR) after primary percutaneous coronary intervention (PCI) in STEMI patients. METHODS: This single-center retrospective study consecutively enrolled STEMI patients who had undergone primary PCI within 12 h from symptom onset. Both angiography and CMR were performed during hospitalization, and patients were divided into low SS (SS ≤ 22), mediate-high SS (SS > 22) groups. Correlation and multivariable analyses were performed. RESULTS: A total of 149 STEMI patients (96 low SS, 53 mediate-high SS) were included. In terms of myocardial injury parameters, there was a positive correlation (p < 0.001, Spearman r = 0.292) between SS and infarct size (IS), and a negative correlation (p < 0.001, Spearman r = - 0.314) between SS and myocardial salvage index (MSI). In the multivariable model, SS (> 22 as categorical variable, OR = 2.245, 95% CI [1.002-5.053], p = 0.048; as continuous variable, OR = 1.053, 95% CI [1.014-1.095], p = 0.008) was significantly associated with high IS (≥ mean 35.43). The areas under the receiver operating characteristic (ROC) curves of SS for high IS and low MSI (≤ median 28.01) were 0.664 and 0.610. CONCLUSIONS: In STEMI patients undergoing primary PCI, SYNTAX score positively correlated with infarct size and negatively with myocardial salvage, indicating an independent predictive value of the myocardial injury.

Computed tomography-based radiomics model for discriminating the risk stratification of gastrointestinal stromal tumors.

PURPOSE: The pathological risk degree of gastrointestinal stromal tumors (GISTs) has become an issue of great concern. Computed tomography (CT) is beneficial for showing adjacent tissues in detail and determining metastasis or recurrence of GISTs, but its function is still limited. Radiomics has recently shown a great potential in aiding clinical decision-making. The purpose of our study is to develop and validate CT-based radiomics models for GIST risk stratification. METHODS: Three hundred and sixty-six patients clinically suspected of primary GISTs from January 2013 to February 2018 were retrospectively enrolled, among which data from 140 patients were eventually analyzed after exclusion. Data from patient CT images were partitioned based on the National Institutes of Health Consensus Classification, including tumor segmentation, radiomics feature extraction and selection. A radiomics model was then proposed and validated. RESULTS: The radiomics signature demonstrated discriminative performance for advanced and nonadvanced GISTs with an area under the curve (AUC) of 0.935 [95% confidence interval (CI) 0.870-1.000] and an accuracy of 90.2% for validation cohort. The radiomics signature demonstrated favorable performance for the risk stratification of GISTs with an AUC of 0.809 (95% CI 0.777-0.841) and an accuracy of 67.5% for the validation cohort. Radiomics analysis could capture features of the four risk categories of GISTs. Meanwhile, this CT-based radiomics signature showed good diagnostic accuracy to distinguish between nonadvanced and advanced GISTs, as well as the four risk stratifications of GISTs. CONCLUSION: Our findings highlight the potential of a quantitative radiomics analysis as a complementary tool to achieve an accurate diagnosis for GISTs.

pPB Peptide-Mediated siRNA-Loaded Stable Nucleic Acid Lipid Nanoparticles on Targeting Therapy of Hepatic Fibrosis.

Hepatic fibrosis is a necessary process in the development of liver diseases such as hepatic cirrhosis and its complications, which has become a serious threat to human health. Currently, antifibrotic drug treatment is ineffective, and one reason should be the lack of liver targeting ability. In this report, polypeptide pPB-modified stable nucleic acid lipid nanoparticles (pPB-SNALPs) were prepared to selectively deliver siRNAs against heat shock protein 47 to the liver for targeted therapy of hepatic fibrosis. First, siRNA sequences with high silencing efficiency were screened based on siRNA transfection efficacy. Then, pPB-SNALPs were prepared, which showed a narrow size distribution with a diameter in the range of 110-130 nm and a neutral z-potential of 0 mV. As evidenced by the in vitro and in vivo targeting study, compared with unmodified SNALP, pPB-SNALP showed increased uptake by LX-2 cells and primary hepatic stellate cells (HSC) of mice in vitro and showed increased liver distribution and HSC uptake in vivo. In addition, pPB-SNALP also exhibited an enhanced inhibitory effect on TAA-induced hepatic fibrosis mice with high gp46 mRNA expression in vivo. In summary, our results demonstrated that pPB-SNALP is an effective liver-targeted delivery system. This study could lay a good foundation for the targeted gene therapy of hepatic fibrosis.

CT differentiation of malignant peritoneal mesothelioma and tuberculous peritonitis.

OBJECTIVE: The aim of this study was to determine which computed tomography (CT) findings were useful in differentiating malignant peritoneal mesothelioma (MPM) and tuberculous peritonitis (TBP). METHODS: CT scans performed in 53 patients with MPM and 27 patients with TBP confirmed by pathology were retrospectively reviewed. The CT findings were evaluated for the morphologic appearance of ascites, peritoneum, mesenterium and omentum involvement, enlarged lymph nodes, solid abdominal viscera infiltration and metastases, and thoracic changes. The Pearson χ (2) test was used to compare differences between groups. RESULTS: Patients in both groups displayed a high proportion of peritoneum and mesenterium thickening. However, there were no obvious differences observed for ascites or swollen lymph nodes. There were significant differences in the following aspects between the two groups: (1) smooth peritoneal thickening was more frequent in patients with TBP, while irregular thickening was more frequently observed in patients with MPM; (2) caked omentum stratification was more common in patients with MPM; (3) mesentery involvement was less commonly observed in patients with TBP; (4) abdominal viscera infiltration and pleural plaques were more common in patients with MPM (46/53 and 48/53, respectively) than in those with TBP (0/27 and 0/27); and (5) more patients in the TBP group (14/27) displayed pleural effusion, and extraperitoneal tuberculosis was more common in patients with TBP (20/27). CONCLUSION: Although most CT findings analyzed are observed in both diseases, each disease has its own several unique characteristics. Therefore, using a combination of CT findings may increase our ability to distinguish TBP from MPM.

MRI findings in 1 case of primary gallbladder lymphoma.

We describe a case of gallbladder extra-nodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-ML). MALT-ML is rare, and its clinical manifestations are lack of specificity. A few cases have been reported, and no characteristic imaging features have been described. We discussed the challenges of MRI in diagnosing MALT-ML of gallbladder, especially in differentiating it from gallbladder cancer. We found a "comb-like" sign in the inner wall of gallbladder on T2WI, which may be helpful in diagnosing gallbladder MALT-ML.

Corrigendum: Prediction of severe CRS and determination of biomarkers in B cell-acute lymphoblastic leukemia treated with CAR-T cells.

[This corrects the article DOI: 10.3389/fimmu.2023.1273507.].