Gsα Regulates Macrophage Foam Cell Formation During Atherosclerosis.

BACKGROUND: Many cardiovascular pathologies are induced by signaling through G-protein-coupled receptors via Gsα (G protein stimulatory α subunit) proteins. However, the specific cellular mechanisms that are driven by Gsα and contribute to the development of atherosclerosis remain unclear. METHODS: High-throughput screening involving data from single-cell and bulk sequencing were used to explore the expression of Gsα in atherosclerosis. The differentially expression and activity of Gsα were analyzed by immunofluorescence and cAMP measurements. Macrophage-specific Gsα knockout (Mac-GsαKO) mice were generated to study the effect on atherosclerosis. The role of Gsα was determined by transplanting bone marrow and performing assays for foam cell formation, Dil-ox-LDL (oxidized low-density lipoprotein) uptake, chromatin immunoprecipitation, and luciferase reporter assays. RESULTS: ScRNA-seq showed elevated Gnas in atherosclerotic mouse aorta's cholesterol metabolism macrophage cluster, while bulk sequencing confirmed increased GNAS expression in human plaque macrophage content. A significant upregulation of Gsα and active Gsα occurred in macrophages from human and mouse plaques. Ox-LDL could translocate Gsα from macrophage lipid rafts in short-term and promote Gnas transcription through ERK1/2 activation and C/EBPß phosphorylation via oxidative stress in long-term. Atherosclerotic lesions from Mac-GsαKO mice displayed decreased lipid deposition compared with those from control mice. Additionally, Gsα deficiency alleviated lipid uptake and foam cell formation. Mechanistically, Gsα increased the levels of cAMP and transcriptional activity of the cAMP response element binding protein, which resulted in increased expression of CD36 and SR-A1. In the translational experiments, inhibiting Gsα activation with suramin or cpGN13 reduced lipid uptake, foam cell formation, and the progression of atherosclerotic plaques in mice in vivo. CONCLUSIONS: Gsα activation is enhanced during atherosclerotic progression and increases lipid uptake and foam cell formation. The genetic or chemical inactivation of Gsα inhibit the development of atherosclerosis in mice, suggesting that drugs targeting Gsα may be useful in the treatment of atherosclerosis.

Paraspeckle protein NONO attenuates vascular calcification by inhibiting bone morphogenetic protein 2 transcription.

Vascular calcification is a pathological process commonly associated with atherosclerosis, chronic kidney disease, and diabetes. Paraspeckle protein NONO is a multifunctional RNA/DNA binding protein involved in many nuclear biological processes but its role in vascular calcification remains unclear. Here, we observed that NONO expression was decreased in calcified arteries of mice and patients with CKD. We generated smooth muscle-specific NONO-knockout mice and established three different mouse models of vascular calcification by means of 5/6 nephrectomy, adenine diet to induce chronic kidney failure, or vitamin D injection. The knockout mice were more susceptible to the development of vascular calcification relative to control mice, as verified by an increased calcification severity and calcium deposition. Likewise, aortic rings from knockout mice showed more significant vascular calcification than those from control mice ex vivo. In vitro, NONO deficiency aggravated high phosphate-induced vascular smooth muscle cell osteogenic differentiation and apoptosis, whereas NONO overexpression had a protective effect. Mechanistically, we demonstrated that the regulation of vascular calcification by NONO was mediated by bone morphogenetic protein 2 (BMP2). NONO directly bound to the BMP2 promoter using its C-terminal region, exerting an inhibitory effect on the transcription of BMP2. Thus, our study reveals that NONO is a novel negative regulator of vascular calcification, which inhibits osteogenic differentiation of vascular smooth muscle cell and vascular calcification via negatively regulating BMP2 transcription. Hence, NONO may provide a promising target for the prevention and treatment of vascular calcification.

Target recognition and segmentation in turbid water using data from non-turbid conditions: a unified approach and experimental validation.

Semantic segmentation of targets in underwater images within turbid water environments presents significant challenges, hindered by factors such as environmental variability, difficulties in acquiring datasets, imprecise data annotation, and the poor robustness of conventional methods. This paper addresses this issue by proposing a novel joint method using deep learning to effectively perform semantic segmentation tasks in turbid environments, with the practical case of efficiently collecting polymetallic nodules in deep-sea while minimizing damage to the seabed environment. Our approach includes a novel data expansion technique and a modified U-net based model. Drawing on the underwater image formation model, we introduce noise to clear water images to simulate images captured under varying degrees of turbidity, thus providing an alternative to the required data. Furthermore, traditional U-net-based modified models have shown limitations in enhancing performance in such tasks. Based on the primary factors underlying image degradation, we propose a new model which incorporates an improved dual-channel encoder. Our method significantly advances the fine segmentation of underwater images in turbid media, and experimental validation demonstrates its effectiveness and superiority under different turbidity conditions. The study provides new technical means for deep-sea resource development, holding broad application prospects and scientific value.

Association between the triglyceride-glucose index and impaired cardiovascular fitness in non-diabetic young population.

BACKGROUND: The triglyceride-glucose (TyG) index has been linked to the onset, progression, and prognosis of cardiovascular disease (CVD) in middle-aged and elderly individuals. Nevertheless, the relationship between the TyG index and impaired cardiovascular fitness (CVF) remains unexplored in non-diabetic young population. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) study (1999-2004) to conduct a cross-sectional study of 3364 participants who completed an examination of CVF. Impaired CVF was defined as low and moderate CVF levels determined by estimated maximal oxygen consumption (Vo2max), based on sex- and age-specific criteria. The TyG index was calculated by [Formula: see text]. RESULTS: The age (median with interquartile range) of the study population was 28 (19-37) years, and the TyG index (median ± standard deviation) was 8.36 ± 0.52. A significant association between the TyG index and impaired CVF was found in multivariable logistical regression analysis (per 1-unit increase in the TyG index: OR, 1.46; 95% Cl 1.13-1.90). A dose‒response relationship between the TyG index and impaired CVF was presented by restricted cubic splines (RCS). A significant interaction (p = 0.027) between sex and the TyG index for impaired CVF was found in the population aged < 20 years. CONCLUSIONS: In non-diabetic young population, individuals with higher TyG index values are at an increased likelihood of encountering impaired CVF. Furthermore, sex may exert an impact on CVF, as males tend to be more susceptible to impaired CVF under comparable TyG index conditions.

Long-term outcomes with HLX01 (HanliKang®), a rituximab biosimilar, in previously untreated patients with diffuse large B-cell lymphoma: 5-year follow-up results of the phase 3 HLX01-NHL03 study.

HLX01 (HanliKang®) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2-76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9-87.5%) and 75.4% (95% CI: 68.9-82.6%)( HR: 0.75, 95% CI 0.47-1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4-84.6%) and 73.0% (95% CI: 66.3-80.3%) (HR: 0.84, 95% CI 0.54-1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.

CEAC (oral semustine, etoposide, cytarabine and cyclophosphamide) vs BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning regimen of autologous stem cell transplantation for diffuse large B-cell lymphoma: a post-hoc, propensity score-matched, cohort study in Chinese patients.

Autologous stem cell transplantation (ASCT) is a salvage therapy for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). We have developed a novel conditioning regimen called CEAC (oral semustine 250 mg/m2 d-6, etoposide 300 mg/m2 d-5 ~ d-2, cytarabine 500 mg/m2 d-5 ~ d-2, and cyclophosphamide 1200 mg/m2 d-5 ~ d-2) In lymphoma patients in China. Here, we conducted a study to compare the conventional BEAM regimen with the CEAC regimen in 110 DLBCL patients. Propensity-score matching was performed in a 1:4 ratio (22 patients received BEAM and 88 received CEAC). Our results showed no significant difference in the overall response rate (95% vs 97%, P = 1.000) and complete response rate (66% vs 73%, P = 0.580) between the two cohorts. The 5-year progression-free survival (PFS), 5-year overall survival (OS), and 5-year cumulative incidence of relapse (CIR) for all patients were 72% (95% CI 62%-82%), 92% (95% CI 86%-97%), and 29% (95% CI 17%-38%), respectively. There was no significant difference in the 5-year PFS (80% vs 70%, P = 0.637), 5-year OS (95% vs 91%, P = 0.496), and 5-year CIR (20% vs 30%, P = 0.733) between cohorts. In terms of safety, the CEAC cohort had a lower incidence rate of grade 1-2 gastrointestinal hemorrhage (P = 0.023) and severe nausea (P = 0.007) compared with the BEAM cohort. In conclusion, the CEAC regimen seems to be a suitable alternative to the BEAM regimen for ASCT in DLBCL patients.

Transcriptome-based network analysis reveals hub immune genes and pathways of hepatopancreas against LPS in Amphioctopus fangsiao.

The hepatopancreas is the biggest digestive organ in Amphioctopus fangsiao (A. fangsiao), but also undertakes critical functions like detoxification and immune defense. Generally, pathogenic bacteria or endotoxin from the gut microbiota would be arrested and detoxified in the hepatopancreas, which could be accompanied by the inevitable immune responses. In recent years, studies related to cephalopods immune have been increasing, but the molecular mechanisms associated with the hepatopancreatic immunity are still unclear. In this study, lipopolysaccharide (LPS), a major component of the cell wall of Gram-negative bacteria, was used for imitating bacteria infection to stimulate the hepatopancreas of A. fangsiao. To investigate the immune process happened in A. fangsiao hepatopancreas, we performed transcriptome analysis of hepatopancreas tissue after LPS injection, and identified 2615 and 1943 differentially expressed genes (DEGs) at 6 and 24 h post-injection, respectively. GO and KEGG enrichment analysis showed that these DEGs were mainly involved in immune-related biological processes and signaling pathways, including ECM-receptor interaction signaling pathway, Phagosome signaling pathway, Lysosome signaling pathway, and JAK-STAT signaling pathways. The function relationships between these DEGs were further analyzed through protein-protein interaction (PPI) networks. It was found that Mtor, Mapk14 and Atm were the three top interacting DEGs under LPS stimulation. Finally, 15 hub genes involving multiple KEGG signaling pathways and PPI relationships were selected for qRT-PCR validation. In this study, for the first time we explored the molecular mechanisms associated with hepatopancreatic immunity in A. fangsiao using a PPI networks approach, and provided new insights for understanding hepatopancreatic immunity in A. fangsiao.

SorCS2 is involved in promoting periodontitis-induced depression-like behaviour in mice.

BACKGROUND: Emerging evidence supports the association between periodontitis and depression, although the mechanisms are unclear. This study investigated the role of SorCS2 in the pathogenesis of periodontitis-induced depression. MATERIALS AND METHODS: An experimental periodontitis model was established using SorCS2 knockout mice and their wild-type littermates, and depression-like behaviour was evaluated. The expression of proBDNF signalling, neuronal activity, and glutamate-associated signalling pathways were further measured by western blotting and immunofluorescence. In addition, neuroinflammatory status, astrocytic and microglial markers, and the expression of corticosterone-related factors were measured by immunofluorescence, western blotting, and enzyme-linked immunosorbent assays. RESULTS: SorCS2 deficiency alleviated periodontitis-induced depression-like behaviour in mice. Further results suggested that SorCS2 deficiency downregulated the expression of pro-BDNF and glutamate signalling and restored neuronal activities in mice with periodontitis. Neuroinflammation in the mouse hippocampus was triggered by experimental periodontitis but was not affected by SorCS2 deficiency. The levels of corticosterone and the expression of glucocorticoid receptors were also not altered. CONCLUSION: Our study, for the first time, reveals the critical role of SorCS2 in the pathogenesis of periodontitis-induced depression. The underlying mechanism involves proBDNF and glutamate signalling in the hippocampus, providing a novel therapeutic target for periodontitis-associated depression.

A Case of Complex Giant Rhinophyma Treated With Cosmetic Surgery.

ABSTRACT: Rhinophyma leads to severe facial deformities and significant social pressure for patients. Patients often seek medical intervention due to cosmetic defects and functional impairments, such as nasal congestion and airway collapse. Currently, there are numerous treatment modalities for rhinophyma, each with distinct advantages and disadvantages, leading to a lack of consensus in nasal vegetation management. Severe thickening in the nasal area can obstruct breathing through external nasal valve blockage, necessitating appropriate management for relief. This article presents a case study involving severe rhinophyma with respiratory obstruction that was successfully treated using incomplete resection followed by reconstruction to restore normal nasal contour. This not only achieved an upright position for nasal columella but also improved nasal contour to achieve normal appearance levels while completely relieving respiratory tract obstruction and enhancing patients' ventilation function. This method is easily performed without requiring additional expensive equipment, making it economically feasible even in ordinary medical centers while enabling patients to achieve a high quality of life.

Three-Stage Interpolation Method for Demosaicking Monochrome Polarization DoFP Images.

The emergence of polarization image sensors presents both opportunities and challenges for real-time full-polarization reconstruction in scene imaging. This paper presents an innovative three-stage interpolation method specifically tailored for monochrome polarization image demosaicking, emphasizing both precision and processing speed. The method introduces a novel linear interpolation model based on polarization channel difference priors in the initial two stages. To enhance results through bidirectional interpolation, a continuous adaptive edge detection method based on variance differences is employed for weighted averaging. In the third stage, a total intensity map, derived from the previous two stages, is integrated into a residual interpolation process, thereby further elevating estimation precision. The proposed method undergoes validation using publicly available advanced datasets, showcasing superior performance in both global parameter evaluations and local visual details when compared with existing state-of-the-art techniques.

Comparative Analysis of the Biochemical Composition, Amino Acid, and Fatty Acid Contents of Diploid, Triploid, and Tetraploid Crassostrea gigas.

Tetraploid oysters are artificially produced oysters that do not exist in nature. The successful breeding of 100% triploid oysters resolved the difficulties of traditional drug-induced triploids, such as the presence of drug residues and a low triploid induction rate. However, little is known concerning the biochemical composition and nutrient contents of such tetraploids. Therefore, we investigated compositional differences among diploid, triploid, and tetraploid Crassostrea gigas as well as between males and females of diploids and tetraploids. The findings indicated that glycogen, EPA, ∑PUFA, and omega-3 contents were significantly higher in triploid oysters than in diploids or tetraploids; tetraploid oysters had a significantly higher protein content, C14:0, essential amino acid, and flavor-presenting amino acid contents than diploids or triploids. For both diploid and tetraploids, females had significantly higher levels of glutamate, methionine, and phenylalanine than males but lower levels of glycine and alanine. In addition, female oysters had significantly more EPA, DHA, omega-3, and total fatty acids, a result that may be due to the fact that gonadal development in male oysters requires more energy to sustain growth, consumes greater amounts of nutrients, and accumulates more proteins. With these results, important information is provided on the production of C. gigas, as well as on the basis and backing for the genetic breeding of oysters.

Preliminary study on toxicological mechanism of golden cuttlefish (Sepia esculenta) larvae exposed to cd.

BACKGROUND: Cadmium (Cd) flows into the ocean with industrial and agricultural pollution and significantly affects the growth and development of economic cephalopods such as Sepia esculenta, Amphioctopus fangsiao, and Loligo japonica. As of now, the reasons why Cd affects the growth and development of S. esculenta are not yet clear. RESULTS: In this study, transcriptome and four oxidation and toxicity indicators are used to analyze the toxicological mechanism of Cd-exposed S. esculenta larvae. Indicator results indicate that Cd induces oxidative stress and metal toxicity. Functional enrichment analysis results suggest that larval ion transport, cell adhesion, and some digestion and absorption processes are inhibited, and the cell function is damaged. Comprehensive analysis of protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore S. esculenta larval toxicological mechanisms, and we find that among the 20 identified key genes, 14 genes are associated with neurotoxicity. Most of them are down-regulated and enriched to the neuroactive ligand-receptor interaction signaling pathway, suggesting that larval nervous system might be destroyed, and the growth, development, and movement process are significantly affected after Cd exposure. CONCLUSIONS: S. esculenta larvae suffered severe oxidative damage after Cd exposure, which may inhibit digestion and absorption functions, and disrupt the stability of the nervous system. Our results lay a function for understanding larval toxicological mechanisms exposed to heavy metals, promoting the development of invertebrate environmental toxicology, and providing theoretical support for S. esculenta artificial culture.

New insights into the clinical characteristics of SETD2-mutated acute myeloid leukaemia.

As reported, SETD2 is recurrently mutated in acute myeloid leukaemia (AML), but knowledge about the specifics is limited. We enrolled 530 consecutive newly diagnosed AML patients in our study, and we analysed the distribution pattern and prognostic role of SETD2 mutation in AML. SETD2 mutation was found to affect 6.3% of AML patients, and it frequently co-occurred with IDH2, NRAS and CEBPA mutations. SETD2-mutated patients saw excellent therapeutic responses but failed to gain better survival time than other patients. This could be because of the high recurrence and mortality in SETD2-mutated patients who have additional mutations, such as NRAS mutation.

Fast image visibility enhancement based on active polarization and color constancy for operation in turbid water.

Vehicles operating in a water medium sometimes encounter harsh conditions with high turbidity and low scene illumination, making it challenging to obtain reliable target information through optical devices. Although many post-processing solutions were proposed, they are not applicable to continuous vehicle operations. Inspired by the advanced polarimetric hardware technology, a joint fast algorithm was developed in this study to address the above problems. Backscatter attenuation and direct signal attenuation were solved separately by utilizing the revised underwater polarimetric image formation model. A fast local adaptive Wiener filtering method was used to improve the backscatter estimation by reducing the additive noise. Further, the image was recovered using the fast local space average color method. By using a low-pass filter guided by the color constancy theory, the problems of nonuniform illumination caused by artificial light and direct signal attenuation were both addressed. The results of testing on images from laboratory experiments showed improved visibility and realistic chromatic rendition.

Triglyceride-glucose index in the prediction of adverse cardiovascular events in patients without diabetes mellitus after coronary artery bypass grafting: a multicenter retrospective cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index has been evaluated as a reliable surrogate for insulin resistance (IR) and has been proven to be a predictor of poor outcomes in patients with cardiovascular diseases. However, data are lacking on the relationship of the TyG index with prognosis in nondiabetic patients who underwent coronary artery bypass grafting (CABG). Thus, the purpose of our current study was to investigate the potential value of the TyG index as a prognostic indicator in patients without diabetes mellitus (DM) after CABG. METHODS: This multicenter, retrospective cohort study involving 830 nondiabetic patients after CABG from 3 tertiary public hospitals from 2014 to 2018. Kaplan-Meier survival curve analysis was conducted followed by the log-rank test. Cox proportional hazards regression models were used to explore the association between the TyG index and major adverse cardiovascular events (MACEs). The incremental predictive power of the TyG index was evaluated with C-statistics, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: An incrementally higher TyG index was associated with an increasingly higher cumulative incidence of MACEs (log-rank test, p < 0.001). The hazard ratio (95% CI) of MACEs was 2.22 (1.46-3.38) in tertile 3 of the TyG index and 1.38 (1.18-1.62) per SD increase in the TyG index. The addition of the TyG index yielded a significant improvement in the global performance of the baseline model [C-statistic increased from 0.656 to 0.680, p < 0.001; continuous NRI (95% CI) 0.269 (0.100-0.438), p = 0.002; IDI (95% CI) 0.014 (0.003-0.025), p = 0.014]. CONCLUSIONS: The TyG index may be an independent factor for predicting adverse cardiovascular events in nondiabetic patients after CABG.

The synergistic effect of the triglyceride-glucose index and serum uric acid on the prediction of major adverse cardiovascular events after coronary artery bypass grafting: a multicenter retrospective cohort study.

BACKGROUND: Elevated serum uric acid (SUA) is regarded as a risk factor for the development of cardiovascular diseases. Triglyceride-glucose (TyG) index, a novel surrogate for insulin resistance (IR), has been proven to be an independent predictor for adverse cardiac events. However, no study has specifically focused on the interaction between the two metabolic risk factors. Whether combining the TyG index and SUA could achieve more accurate prognostic prediction in patients undergoing coronary artery bypass grafting (CABG) remains unknown. METHODS: This was a multicenter, retrospective cohort study. A total of 1225 patients who underwent CABG were included in the final analysis. The patients were grouped based on the cut-off value of the TyG index and the sex-specific criteria of hyperuricemia (HUA). Cox regression analysis was conducted. The interaction between the TyG index and SUA was estimated using relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). The improvement of model performance yielded by the inclusion of the TyG index and SUA was examined by C-statistics, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). The goodness-of-fit of models was evaluated using the Akaike information criterion (AIC), Bayesian information criterion (BIC) and χ2 likelihood ratio test. RESULTS: During follow-up, 263 patients developed major adverse cardiovascular events (MACE). The independent and joint associations of the TyG index and SUA with adverse events were significant. Patients with higher TyG index and HUA were at higher risk of MACE (Kaplan-Meier analysis: log-rank P < 0.001; Cox regression: HR = 4.10; 95% CI 2.80-6.00, P < 0.001). A significant synergistic interaction was found between the TyG index and SUA [RERI (95% CI): 1.83 (0.32-3.34), P = 0.017; AP (95% CI): 0.41 (0.17-0.66), P = 0.001; SI (95% CI): 2.13 (1.13-4.00), P = 0.019]. The addition of the TyG index and SUA yielded a significant improvement in prognostic prediction and model fit [change in C-statistic: 0.038, P < 0.001; continuous NRI (95% CI): 0.336 (0.201-0.471), P < 0.001; IDI (95% CI): 0.031 (0.019-0.044), P < 0.001; AIC: 3534.29; BIC: 3616.45; likelihood ratio test: P < 0.001). CONCLUSIONS: The TyG index interacts synergistically with SUA to increase the risk of MACE in patients undergoing CABG, which emphasizes the need to use both measures concurrently when assessing cardiovascular risk.

Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy.

Hematotoxicity is the most common long-term adverse event (AE) after chimeric antigen receptor T-cell (CAR T) therapy. However, patients who receive CAR T therapy in pivotal clinical trials are subjected to restrictive selection criteria, and this means that rare but fatal toxicities are underestimated. Here, we systematically analyzed CAR T-associated hematologic AE using the US Food and Drug Administration Adverse Event Reporting System (FAERS) between January 2017 and December 2021. Disproportionality analyses were performed using reporting odds ratios (ROR) and information component (IC); the lower limit of the ROR and IC 95% confidence interval (CI) (ROR025 and IC025) exceeding one and zero was considered significant, respectively. Among the 105,087,611 reports in FAERS, 5,112 CAR T-related hematotoxicity reports were identified. We found 23 significant over-reporting hematologic AE (ROR025 >1) compared to the full database, of which hemophagocytic lymphohistiocytosis (HLH; n=136 [2.7%], ROR025 = 21.06), coagulopathy (n=128 [2.5%], ROR025 = 10.43), bone marrow failure (n=112 [2.2%], ROR025 = 4.88), disseminated intravascular coagulation (DIC; n=99 [1.9%], ROR025 = 9.64), and B-cell aplasia (n=98 [1.9%], ROR025 = 118.16, all IC025 > 0) were highly under-reported AE in clinical trials. Importantly, HLH and DIC led to mortality rates of 69.9% and 59.6%, respectively. Lastly, hematotoxicity-related mortality was 41.43%, and 22 death-related hematologic AE were identified using LASSO regression analysis. These findings could help clinicians in the early detection of those rarely reported but lethal hematologic AE, thus reducing the risk of severe toxicities for CAR T recipients.

Combination of the triglyceride-glucose index and EuroSCORE II improves the prediction of long-term adverse outcomes in patients undergoing coronary artery bypass grafting.

AIMS: We aimed to investigate the independent and combined association of the triglyceride-glucose (TyG) index and EuroSCORE II with major adverse cardiovascular event (MACE) after coronary artery bypass grafting (CABG), and examine whether the addition of the TyG index improves the predictive performance of the EuroSCORE II. MATERIALS AND METHODS: This study included 1013 patients who underwent CABG. The primary endpoint was MACE, which was defined as the composite of all-cause death, repeat coronary artery revascularisation, non-fatal myocardial infarction and non-fatal stroke. The patients were grouped by the TyG index and EuroSCORE II tertiles and the combination of these risk indicators. RESULTS: During the follow-up, 211 individuals developed MACE. Elevated levels of the TyG index and EuroSCORE II were associated with an increased risk of MACE. The hazard ratio [95% confidence interval (CI)] was 3.66 (2.34-5.73) in patients with the highest tertile of the TyG index and EuroSCORE II. Compared with the EuroSCORE II alone, combining the TyG index with EuroSCORE II achieved a better predictive performance [C-statistic increased 0.032, p < 0.001; continuous net reclassification improvement (NRI) (95% CI): 0.364 (0.215-0.514), p < 0.001; integrated discrimination improvement (IDI) (95% CI): 0.015 (0.007-0.023), p < 0.001, Akaike's information criteria (AIC) and Bayesian information criterion (BIC) decreased, and the likelihood ratio test, p < 0.001]. CONCLUSIONS: The TyG index and EuroSCORE II are independently associated with poor prognosis. Furthermore, the TyG index is an important adjunct to the EuroSCORE II for improving risk stratification and guiding early intervention among post-CABG patients.

Re-induction therapy in patients with acute myeloid leukemia not in complete remission after the first course of treatment.

A standard salvage regimen for patients with acute myeloid leukemia (AML) who are not in complete remission (CR) after initial induction therapy does not exist. We retrospectively investigated re-induction therapy for 151 patients with AML who did not achieve CR after the initial course between January 2014 and March 2021. The re-induction regimen did not correlate with the CR rate after the second course, whereas patients had similar 5-year overall survival (OS) and event-free survival (EFS) based on different re-induction regimens. Multivariable analysis revealed that International European Leukaemia Net (ELN) risk stratification independently predicted both OS and EFS among patients not in CR after the first course, although the re-induction regimen did not predict prognosis. Urgent salvage alloHSCT may improve the prognosis of patients with refractory AML. In summary, our study showed that the re-induction regimen did not significantly predict the prognosis of patients with AML not in CR after the first course of treatment. The development and selection of an efficient treatment algorithm for the treatment of AML remains a pressing research challenge.

Cytogenetic evolution predicts a poor prognosis in acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation.

Acute myeloid leukemia (AML) patients relapsing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a poor prognosis. Cytogenetic evolution (CGE) has been investigated and found to have an important impact on the prognosis of relapsed leukemia, but its impact on AML patients relapsing after transplantation remains controversial. In this study, we analyzed 34 AML patients relapsing after allo-HSCT, among whom 14 developed additional abnormalities in chromosomal karyotype after leukemia recurrence (CGE group) and 20 patients did not (non-CGE group). We found that the cytogenetic characteristics were much more complex at relapse in the CGE group, and the acquisition of aberrations at relapse most commonly involved chromosome 11. The 6-month post-relapse overall survival (PROS) of the CGE group was significantly lower than that of the non-CGE group (21.4% versus 50.0%, P = 0.004). The CGE group also showed a trend of worse 2-year OS (7.1% versus 28.6%, P = 0.096). In the multivariate analyses, the occurrence of chronic graft-versus-host disease (HR 0.27 [95% CI, 0.11-0.68], P = 0.006) and a reduced-intensity FBA conditioning regimen (HR 0.42 [95% CI, 0.18-0.98], P = 0.045) were found to be two independent factors for a better PROS, whereas CGE (HR 3.16 [95% CI, 1.42-7.05], P = 0.005) was associated with a worse PROS. In conclusion, CGE was associated with a poor prognosis in AML patients who relapsed after allo-HSCT, and the importance of monitoring karyotype changes after transplantation should be noted.