Nontraditional translation is the key to UFMylation and beyond.

The Ubiquitin-fold modifier 1 (Ufm1) is a ubiquitin-like protein that can also be conjugated to protein substrates and subsequently alter their fates. Both UFMylation and de-UFMylation are mediated by Ufm1-specific proteases (UFSPs). In humans, it is widely believed that UFSP2 is the only active Ufm1 protease involved in Ufm1 maturation and de-UFMylation, whereas UFSP1 is thought to be inactive. Here, Liang et al. provide strong evidence showing that human UFSP1 is also an active Ufm1 protease. These results solve an age-old mystery in the human Ufm1 conjugation system and could have a greater impact not only on Ufm1 biology but also on the translation of genes employing nontraditional start codons.

Association between diet quality scores and risk of overweight and obesity in children and adolescents.

BACKGROUND: This study examined the associations of diet quality assessed by Healthy Eating Index 2015 (HEI-2015), Alternative Healthy Eating Index 2010 (AHEI-2010), Mediterranean Diet (MedDiet) and overweight/obesity in children and adolescents. METHODS: This cross-sectional study used data of participants aged 2-19 years from National Health and Nutrition Examination Survey (NHANES) 2005-2018. The weighted logistic regression model was adopted to explore the association between diet quality scores and overweight, obesity in children and adolescents. Subgroup analysis was also performed based on sex. RESULTS: A total of 9,724 participants were included in children group (2-11 years old), and 5,934 were adolescent group (12-19 years old). All participants were divided into based on the BMI-for-age: underweight and normal, overweight and obesity groups. After adjusting for age, race, poverty-income ratio, maternal smoking during pregnancy and total energy, HEI-2015 and MedDiet scores were related to the risk of overweight in children, and only MedDiet scores remained associated with a decreased risk of obesity in children. MedDiet scores were associated with a decreased risk of overweight, obesity in adolescents, respectively, after adjusting age, sex, race, poverty-income ratio, cotinine, total energy and physical activity. The similar results in male participants were also found. CONCLUSION: Higher MedDiet scores were associated with lower the risk of overweight and obesity, respectively, particularly for male children and adolescents. The higher HEI-2015 scores were also related to the risk of overweight in children.

Feedback regulation of auxin signaling through the transcription of H2A.Z and deposition of H2A.Z to SMALL AUXIN UP RNAs in Arabidopsis.

Auxin is a critical phytohormone that is involved in the regulation of most plant growth and developmental responses. In particular, epigenetic mechanisms, like histone modifications and DNA methylation, were reported to affect auxin biosynthesis and transport. However, the involvement of other epigenetic factors, such as histone variant H2A.Z, in the auxin-related developmental regulation remains unclear. We report that the histone variant H2A.Z knockdown mutant in Arabidopsis Col-0 ecotype, h2a.z-kd, has more lateral roots and weak gravitational responses related to auxin-regulated growth performances. Further study revealed that auxin promotes the eviction of H2A.Z from the auxin-responsive genes SMALL AUXIN-UP RNAs (SAURs) to activate their transcriptions. We found that IAA promotes the transcription of H2A.Z genes through HOMEOBOX PROTEIN 22/25 (AtHB22/25) transcription factors which work as downstream targets of ARF7/19 in auxin signaling. Double mutant of hb22 hb25 showed similar lateral root and gravitropism phenotypes to h2a.z-kd. Our results shed light on a reciprocal regulation hub through INOSITOL AUXOTROPHY 80-mediated H2A.Z eviction and ARF7/19-HB22/25-mediated H2A.Z transcription to modulate the activation of SAURs and plant growth in Arabidopsis.

Antifungal Strategy in Patients with Invasive Fungal Disease Associated with Hematological Malignancies Based on Risk Stratification.

Patients with hematological malignancies (HM) often develop the invasive fungal disease (IFD), causing important morbidity/mortality. While treatment guidelines are available, risk stratification models for optimizing antifungal therapy strategies are few. Clinical records from 458 HM patients with IFD were retrospectively analyzed. Following Chinese treatment guidelines, patients received empirical (n = 239) or diagnostic-driven therapy (n = 219). The effectiveness rate was 87.9% for the empirical and 81.7% for the diagnostic-driven therapy groups (P ≥ 0.05). The incidence of adverse reactions was 18.4% and 16.9%, respectively (P ≥ 0.05). All risk factors of IFD in HM patients were estimated in the univariate analyses and multivariate analyses by the chi-square test and logistic regression model. Duration ≥14 days (OR = 18.340, P=0.011), relapsed/refractory disease (OR = 11.670, P=0.005), IFD history (OR = 5.270, P=0.021), and diabetes (OR = 3.120, P=0.035) were significantly associated with IFD in the multivariate analysis. Patients with more than 3 of these factors have a significant difference in effective rates between the empirical (85.7%) and diagnostic-driven (41.6%) therapy (P=0.008). Empirical and diagnostic-driven therapy effective rates were 80.6% and 70.9% in the patients with two risk factors (P > 0.05) and 85.1% and 85.4% in the patients with one risk factor (P > 0.05). Thus, there was no significant difference in effectiveness in patients with one or two risk factors. The abovementioned risk stratification can guide clinical antifungal therapy. The patients with 3 or more risk factors benefit from empirical therapy.

Mesenchymal stem cells enhance the impact of KIR receptor-ligand mismatching on acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia but not in those with acute lymphocytic leukemia.

Killer cell immunoglobulin-like receptor (KIR) receptor-ligand mismatch has been shown to be protective for acute and chronic graft-versus-host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia. Mesenchymal stem cells (MSC) have been considered as one of the most promising prophylaxis for severe GVHD. However, there are no prospective or retrospective studies determining whether they can work synergistically on GVHD. To investigate the potential influence of KIR matching and MSCs, and their synergism on aGVHD and cGVHD after allo-HSCT in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. Data from 104 patients with AML and 50 patients with ALL treated with allo-HSCT in the transplantation unit were retrospectively analyzed. KIR genotyping was performed by the PCR-SSO method. The amplicons were quantified on the Luminex 200 flow analyzer and analyzed using the Quick-Type for Lifecodes software to generate KIR data. Cox proportional hazards models were used in multivariate analyses. KIR receptor-ligand matching was associated with an increased risk of grade II-IV aGVHD compared to KIR receptor-ligand mismatching (p < 0.001) in AML patients, but KIR ligand-mismatching had no significant effect on aGVHD or cGVHD in ALL patients. In contrast, MSCs reduced the incidence of grade II-IV aGVHD in both AML and ALL patients (AML: p = 0.006; ALL: p = 0.008) regardless of KIR mismatching. The combination of KIR receptor-ligand mismatch and MSC transplantation significantly suppressed grade II-IV aGVHD occurrence in AML patients (p = 0.039). In the KIR mismatch group, the incidence of aGVHD was 2.8% in patients receiving MSC compared to 14.6% in those who did not (p = 0.047). KIR receptor-ligand mismatch, MSC transplantation and their combined use significantly reduced the risk of aGVHD after allo-HSCT. These data provide a clinically applicable strategy to reduce aGVHD, thus improving allo-HSCT outcome.

Anti-Inflammatory Effect of Curcumin on the Mouse Model of Myocardial Infarction through Regulating Macrophage Polarization.

Inflammation causes tissue damage and promotes ventricular remodeling after myocardial infarction (MI), and the infiltration and polarization of macrophages play an important role in regulating inflammation post-MI. Here, we investigated the anti-inflammatory function of curcumin after MI and studied its relationship with macrophage polarization. In vivo, curcumin not only attenuated ventricular remodeling 3 months after MI but also suppressed inflammation during the first 7 days post-MI. Importantly, the results of qPCR and immunochemistry showed that curcumin decreased M1 (iNOS, CCL2, and CD86) but increased M2 macrophage (Arg1, CD163, and CD206) marker expression in the myocardium of MI mice during the first 7 days post-MI. And flow cytometry analysis indicated that curcumin suppressed M1 (CD45+Gr-1-CD11b+iNOS+ cells) but enhanced M2 macrophage (CD45+Gr-1-CD11b+Arg+ cells) expansion in the myocardium of MI mice during the first 7 days post-MI. In vitro, curcumin decreased LPS/IFNγ-elevated M1 macrophage marker (iNOS and CD86) expression and the proportion of M1 macrophages (iNOS+F4/80+ cells) but increased LPS/IFNγ-suppressed M2 macrophage marker (Arg1 and CD206) expression and the proportion of M2 macrophages (Arg1+F4/80+ cells). In addition, curcumin modulates M1/M2 macrophage polarization partly via AMPK. In conclusion, curcumin suppressed the MI-induced inflammation by modulating macrophage polarization partly via the AMPK pathway.

Exploring the potential of photosynthetic induction factor for the commercial production of fucoxanthin in Phaeodactylum tricornutum.

Currently, the market price of fucoxanthin-based drugs remains high primarily because, on one hand, the main natural source of fucoxanthin, Phaeodactylum tricornutum (P. tricornutum), is extremely low in endogenous fucoxanthin, while, on the other hand, fucoxanthin mass production has proved to be very challenging. In this study, we demonstrated the feasibility of increasing fucoxanthin bioaccumulation in P. tricornutum by promoting photosynthetic activity of this diatom. Specifically, this study investigated the effects of different concentrations of the photosynthetic induction factor (PIF) on fucoxanthin content and biosynthesis, on chlorophyll fluorescence characteristics, and on the expression of photosynthesis-related genes in P. tricornutum. The results showed that the optimal PIF concentration was 1 µg L-1, while optimal time was 48 h, with the effect decreasing at 72 h. Fucoxanthin content increased by 44.2% compared to that of the control group in 48 h. Correlation analysis showed a significant positive correlation between fucoxanthin content and the actual photosynthetic yield of PS II (r = 0.949, P < 0.01). The total amount of energy actually used in photosystem II (PS II) by photosynthesis may be used as the main components affecting the biosynthesis of fucoxanthin in P. tricornutum. In addition, we found that using PIF to promote photosynthesis in P. tricornutum effectively increased the growth rate and bioaccumulation of fucoxanthin to an economically advantageous level, thereby providing a novel strategy for the commercial production of fucoxanthin.

Regional cerebral blood flow correlates eating abnormalities in frontotemporal dementia.

BACKGROUND: Eating abnormalities are one of the core symptoms of frontotemporal dementia (FTD), especially for behavioral variant FTD (bvFTD), and semantic variant primary progressive aphasia (svPPA). METHODS: A group of FTD patients (43 bvFTD, 29 svPPA) underwent single-photon emission CT (SPECT) to measure the region cerebral blood flow (rCBF). The Cambridge Behavioral Inventory (CBI) was used to measure the eating abnormalities. A whole-brain voxel-based correlation between eating abnormalities and rCBF was investigated. RESULTS: In bvFTD, the sweet preference was correlated with decreased rCBF in the bilateral gyrus rectus and temporal pole, and eating the same food was correlated with the left ventral anterior cingulate cortex. In svPPA, decreased rCBF in the left inferior temporal gyrus was correlated with eating the same food. CONCLUSIONS: These findings showed that either different symptoms in the same subtype or the same symptom in different subtypes of FTD may be correlated with different regions, indicating different neural mechanisms behind them.

The effectiveness of intra-aortic balloon pump for myocardial infarction in patients with or without cardiogenic shock: a meta-analysis and systematic review.

BACKGROUND: Conflicting reports on the efficacy of intra-aortic balloon pump (IABP) during percutaneous coronary intervention (PCI) incited us to evaluate the utility of IABP in patients with acute myocardial infarction (AMI). METHODS: Randomized clinical trials comparing patients, who received IABP vs. control (no IABP) during PCI, were hand-searched from MEDLINE, Cochrane, and EMBASE databases using the terms "intra-aortic balloon pump, percutaneous coronary intervention, myocardial infarction, acute coronary syndrome". Mortality rate (30-day and 6-month mortality) was the primary outcome, while the secondary outcomes included 30-day bleeding rate, reinfarction rate, revascularization rate and stroke rate. RESULTS: Pooled results of the seven trials identified indicated that the 30-day and 6-month mortality rate were not significantly different between the IABP and control groups. However, in patients with MI, but without cardiogenic shock (CS), IABP was associated with lower odds of 30-day mortality (OR = 0.35, p = 0.015) and 6-month mortality (OR = 0.41, p = 0.020). The pooled results of 30-day bleeding rate was not significantly higher in patients with IABP than the control group, but for the patients with high risk PCI without CS, it was higher in patients with IABP than the control group (OR = 1.58, p = 0.009). The re-infarction, revascularization, and the stroke rate at 30 days of follow-up were not significantly different between the two groups. CONCLUSIONS: The present results do not favor the clinical utility of IABP in patients suffering high-risk PCI without CS and AMI complicated with CS. However, in patients with AMI, but without CS, IABP may reduce the 30-day and 6-month mortality rate.

Surface-SOS: Self-Supervised Object Segmentation via Neural Surface Representation.

Self-supervised Object Segmentation (SOS) aims to segment objects without any annotations. Under conditions of multi-camera inputs, the structural, textural and geometrical consistency among each view can be leveraged to achieve fine-grained object segmentation. To make better use of the above information, we propose Surface representation based Self-supervised Object Segmentation (Surface-SOS), a new framework to segment objects for each view by 3D surface representation from multi-view images of a scene. To model high-quality geometry surfaces for complex scenes, we design a novel scene representation scheme, which decomposes the scene into two complementary neural representation modules respectively with a Signed Distance Function (SDF). Moreover, Surface-SOS is able to refine single-view segmentation with multi-view unlabeled images, by introducing coarse segmentation masks as additional input. To the best of our knowledge, Surface-SOS is the first self-supervised approach that leverages neural surface representation to break the dependence on large amounts of annotated data and strong constraints. These constraints typically involve observing target objects against a static background or relying on temporal supervision in videos. Extensive experiments on standard benchmarks including LLFF, CO3D, BlendedMVS, TUM and several real-world scenes show that Surface-SOS always yields finer object masks than its NeRF-based counterparts and surpasses supervised single-view baselines remarkably. Code is available at: https://github.com/zhengxyun/Surface-SOS.

Association between Dietary Inflammatory Index (DII) and sarcopenia in ischemic heart disease: an 1999-2004 NHANES study of 1088 US individuals.

BACKGROUND: The aim of this study was to investigate the relationship between DII and sarcopenia in individuals with ischemic heart disease (IHD). METHODS: This was a retrospective study utilizing data of the National Health and Nutrition Examination Survey (NHANES) from 1999-2004. Adults aged ≥50 years diagnosed with IHD, having complete 24-hour dietary recall data, and dual energy X-ray absorptiometry (DEXA)-measured muscle mass were eligible for inclusion. Association between DII and sarcopenia, defined by reduced appendicular skeletal muscle mass, was determined by the logistic regression analyses. RESULTS: Data of 1088 individuals were analyzed, with the mean age of 68.1±0.5 years. Significantly higher DII was observed in the sarcopenic group compared to the non-sarcopenic group (0.24 vs. -0.17, P=0.020). After adjusting for relevant confounders in the multivariable analysis, each unit increase in DII was significantly associated with higher odds of sarcopenia (adjusted odd ratio [aOR]=1.07, 95% confidence interval: 1.00-1.14, P value = 0.040). In stratified analyses, among patients with a Body Mass Index (BMI) ≥30 kg/m2, both DII tertile 2 and tertile 3 were significantly associated with greater odds of sarcopenia (tertile 2 vs. tertile 1: aOR=2.85, 95% CI: 1.56-5.23, P=0.001; tertile 3 vs. tertile 1: aOR=3.11, 95% CI: 1.53-6.31, P=0.002), whereas no significant associations was observed among patients with a BMI<30 kg/m2. CONCLUSIONS: This study has established a significant independent association between a higher DII and an increased risk of sarcopenia in US adults with IHD regardless of type of IHD. BMI appears as a moderating factor in this association.

Clinical characteristics, genetic alterations, and prognosis of adult T-cell leukemia/lymphoma: an 11-year multicenter retrospective study in China.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis, and there is little data available from the Chinese population. This retrospective study included 115 patients diagnosed with ATLL who were treated across five hospitals in China from June 2011 to December 2022. The median age at diagnosis was 53 years. Several genes involved in T-cell receptor-induced nuclear factor κB (TCR-NF-κB) signaling were commonly mutated, including PLCG1, CIC, PRKCB, CARD11, and IRF4. Eighty-seven patients received chemotherapy. Of these, 13 received a hematopoietic stem cell transplant (HSCT) (allogeneic-HSCT, n=9; autologous-HSCT, n=4) after chemotherapy. Following initial multiagent chemotherapy using EPOCH/CHOEP and other regimens, the overall response rates were 80.6% (complete response [CR], 44.4%) and 42.8% (CR, 14.2%), respectively. The 4-year survival rates (median survival time in days) for EPOCH/CHOEP (n=43), HSCT (n=13), and CHOP-based regimens (n=31) were 12.7% (138), 30.8% (333), and 0% (66), respectively. Lymphadenopathy, EPOCH/CHOEP, and hematopoietic stem cell transplantation were independent prognostic protective factors in patients with aggressive ATLL. Chinese patients exhibit a higher incidence of aggressive-type ATLL, sharing similar genetic alterations with Japanese patients. Etoposide-based chemotherapy (EPOCH or CHOEP) remains the preferred choice for aggressive ATLL, and upfront allogeneic HSCT should be considered in all eligible patients.

Classification of autism spectrum disorder using electroencephalography in Chinese children: a cross-sectional retrospective study.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by diverse clinical features. EEG biomarkers such as spectral power and functional connectivity have emerged as potential tools for enhancing early diagnosis and understanding of the neural processes underlying ASD. However, existing studies yield conflicting results, necessitating a comprehensive, data-driven analysis. We conducted a retrospective cross-sectional study involving 246 children with ASD and 42 control children. EEG was collected, and diverse EEG features, including spectral power and spectral coherence were extracted. Statistical inference methods, coupled with machine learning models, were employed to identify differences in EEG features between ASD and control groups and develop classification models for diagnostic purposes. Our analysis revealed statistically significant differences in spectral coherence, particularly in gamma and beta frequency bands, indicating elevated long range functional connectivity between frontal and parietal regions in the ASD group. Machine learning models achieved modest classification performance of ROC-AUC at 0.65. While machine learning approaches offer some discriminative power classifying individuals with ASD from controls, they also indicate the need for further refinement.

Reactivation of cytomegalovirus and bloodstream infection and its impact on early survival after allogeneic haematopoietic stem cell transplantation: a multicentre retrospective study.

Cytomegalovirus reactivation (CMVr) and bloodstream infections (BSI) are the most common infectious complications in patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Both are associated with great high morbidity whilst the BSI is the leading cause of mortality. This retrospective study evaluated the incidence of CMVr and BSI, identified associated risk factors, assessed their impact on survival in allo-HSCT recipients during the first 100 days after transplantation. The study comprised 500 allo-HSCT recipients who were CMV DNA-negative and CMV IgG-positive before allo-HSCT. Amongst them, 400 developed CMVr and 75 experienced BSI within 100 days after allo-HSCT. Multivariate regression revealed that graft failure and acute graft-versus-host disease were significant risk factors for poor prognosis, whereas CMVr or BSI alone were not. Amongst all 500 patients, 56 (14%) developed both CMVr and BSI in the 100 days after HSCT, showing significantly reduced 6-month overall survival (p = 0.003) and long-term survival (p = 0.002). Specifically, in the initial post-transplant phase (within 60 days), BSI significantly elevate mortality risk, However, patients who survive BSI during this critical period subsequently experience a lower mortality risk. Nevertheless, the presence of CMVr in patients with BSI considerably diminishes their long-term survival prospects. This study provides real-world data on the impact of CMVr and BSI following transplantation on survival, particularly in regions such as China, where the prevalence of CMV IgG-positivity is high. The findings underscore the necessity for devising and executing focused prevention and early management strategies for CMVr and BSI to enhance outcomes for allo-HSCT recipients.

The RNF214-TEAD-YAP signaling axis promotes hepatocellular carcinoma progression via TEAD ubiquitylation.

RNF214 is an understudied ubiquitin ligase with little knowledge of its biological functions or protein substrates. Here we show that the TEAD transcription factors in the Hippo pathway are substrates of RNF214. RNF214 induces non-proteolytic ubiquitylation at a conserved lysine residue of TEADs, enhances interactions between TEADs and YAP, and promotes transactivation of the downstream genes of the Hippo signaling. Moreover, YAP and TAZ could bind polyubiquitin chains, implying the underlying mechanisms by which RNF214 regulates the Hippo pathway. Furthermore, RNF214 is overexpressed in hepatocellular carcinoma (HCC) and inversely correlates with differentiation status and patient survival. Consistently, RNF214 promotes tumor cell proliferation, migration, and invasion, and HCC tumorigenesis in mice. Collectively, our data reveal RNF214 as a critical component in the Hippo pathway by forming a signaling axis of RNF214-TEAD-YAP and suggest that RNF214 is an oncogene of HCC and could be a potential drug target of HCC therapy.

Spatiotemporal characteristic analysis of PM2.5 in central China and modeling of driving factors based on MGWR: a case study of Henan Province.

Since the start of the twenty-first century, China's economy has grown at a high or moderate rate, and air pollution has become increasingly severe. The study was conducted using data from remote sensing observations between 1998 and 2019, employing the standard deviation ellipse model and spatial autocorrelation analysis, to explore the spatiotemporal distribution characteristics of PM2.5 in Henan Province. Additionally, a multiscale geographically weighted regression model (MGWR) was applied to explore the impact of 12 driving factors (e.g., mean surface temperature and CO2 emissions) on PM2.5 concentration. The research revealed that (1) Over a period of 22 years, the yearly mean PM2.5 concentrations in Henan Province demonstrated a trend resembling the shape of the letter "M", and the general trend observed in Henan Province demonstrated that the spatial center of gravity of PM2.5 concentrations shifted toward the north. (2) Distinct spatial clustering patterns of PM2.5 were observed in Henan Province, with the northern region showing a primary concentration of spatial hot spots, while the western and southern areas were predominantly characterized as cold spots. (3) MGWR is more effective than GWR in unveiling the spatial heterogeneity of influencing factors at various scales, thereby making it a more appropriate approach for investigating the driving mechanisms behind PM2.5 concentration. (4) The results acquired from the MGWR model indicate that there are varying degrees of spatial heterogeneity in the effects of various factors on PM2.5 concentration. To summarize the above conclusions, the management of the atmospheric environment in Henan Province still has a long way to go, and the formulation of relevant policies should be adapted to local conditions, taking into account the spatial scale effect of the impact of different influencing factors on PM2.5.

Construction and Validation of a Predictive Nomogram Based on Ultrasound for Lymph Node Metastasis of Papillary Thyroid Carcinoma in the Cervical Central Region.

ABSTRACT: To establish and validate a nomogram for predicting lymph node metastasis (LNM) of papillary thyroid carcinoma (PTC) in the cervical central region. This retrospective study included 287 PTC patients with 309 nodules treated from December 2018 to May 2020 at our hospital. The cohort was divided randomly into a training set and a testing set according to a 7:3 ratio. The training set contained 216 nodules, and the testing set contained 93 nodules. The nomogram was developed using the training set, and the data of the testing set were used to validate the performance of nomogram. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. The study showed multifocality, thyroid lesion size, and American College of Radiology Thyroid Imaging, Reporting and Data System (TI-RADS) score were significantly independently associated with LNM in the cervical central region. In the testing set, the calibration curve showed that the nomogram had good discrimination with a C-index of 0.775 (95% confidence interval, 0.680-0.869) and adequate calibration ( P = 0.808). By decision curve analysis and clinical impact curve analysis, the nomogram was shown to have a satisfactory net benefit between thresholds of 0.40 and 0.75. The nomogram can be used for predicting LNM of PTC in the cervical central region and may provide valuable guidance for planning the surgical treatment of PTC patients.

Triterpenoids from the genus Ilex attenuate free fatty acid-induced lipid accumulation in HepG2 cells by regulating lipid metabolism disorder and the AMPK signalling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Various traditional Chinese medicines from the genus Ilex (Aquifoliaceae) have been reported to have excellent hypolipidaemic effects. Although triterpenoids have been found to be the main active components, the underlying mechanisms have not been clarified. AIM OF THE STUDY: This study aimed to investigate the lipid-lowering effect, structure-activity relationship and action mechanism of triterpenoids from the genus Ilex. MATERIALS AND METHODS: FFA was used to induce HepG2 cells to establish a classical lipid-lowering activity screening model for the activities of 31 triterpenoids, and the contents of intracellular lipids, TC, and TG were measured. Furthermore, the structure-activity relationship was discussed. Mechanistically, UPLC-Q/TOF-MS-based metabolomics and lipidomics studies were performed, and metabolic pathways were analysed to investigate the lipid-lowering mechanism. Moreover, western blotting was performed to analyse the expression of key proteins of lipid metabolism and predict the targets of action. RESULTS: Thirteen triterpenoids significantly reduced intracellular lipid accumulation and decreased the levels of TG and TC. Among them, rotundic acid (RA) showed stronger lipid-lowering activity than the simvastatin-positive group, and structure-activity relationship analysis indicated that the hydroxyl groups at C-3 and C-19, hydroxymethyl groups at C-23, and carboxyl groups at C-28 may be the key groups for biological activity. Twenty-two metabolites in the metabolomics study and 19 metabolites in the lipidomics study were identified. The identified biomarkers were primarily glycerophosphocholine, LysoPCs, PCs, TAGs, LysoPEs, LysoPIs and sphingolipids, which are involved in glycerophospholipid and sphingolipid metabolism. Moreover, western blotting analysis showed that the expression of SREBP-1 and HMGCR decreased, while AMPK and ACC phosphorylation and the expression of CPT1A and CYP7A1 increased in the RA-treated group. CONCLUSION: The results suggested that triterpenoids from the genus Ilex showed significant lipid-lowering effects and that RA may be a novel hypolipidaemic drug candidate. Moreover, the underlying mechanism indicated that RA showed a lipid-lowering effect by regulating glycerophospholipid and sphingolipid metabolism and activating the AMPK pathway.

Clinical characteristics and prognosis of patients with co-existing follicular lymphoma and diffuse large B-cell lymphoma components in rituximab era.

PURPOSE: This single-centre study aimed to determine the clinicopathological characteristics and prognosis for patients with co-existing FL and DLBCL components (FL/DLBCL). METHODS: We retrospectively analysed the clinical characteristics and prognosis of patients diagnosed with FL/DLBCL (n = 56) and with pure FL (n = 260) or de novo DLBCL (n = 812) (controls) between January 2013 and December 2021. RESULTS: The median age of patients with FL/DLBCL was 52 years. The amount of the DLBCL component ranged from 5 to 95%. Among the 56 FL/DLBCL cases analysed, 67.9% were of germinal centre B-cell (GCB) origin, 26.8% non-GCB origin, and 5.3% were unclassified. The clinical features of patients with FL/DLBCL were intermediate, falling between those of FL and DLBCL. Propensity-score matching was performed for patients with similar baseline characteristics who were receiving the rituximab plus cyclophosphamide, doxorubicin or epirubicin, vindesine, and prednisone (R-CHOP) regimen. Patients with FL/DLBCL showed inferior outcomes compared to those with FL, with a lower complete remission (CR) rate, progression-free survival (PFS), and overall survival (OS). Bone marrow involvement and B symptoms were identified as independent adverse prognostic factors for PFS among patients with FL/DLBCL. Patients with FL/DLBCL presented a lower CR rate and PFS but similar OS to those with DLBCL when receiving the R-CHOP regimen. CONCLUSION: Patients with FL/DLBCL showed inferior treatment response and survival than those with pure FL and had a lower CR rate and PFS, but similar OS to those with DLBCL in the rituximab era.

[A Retrospective Study on the Efficacy and Safety of Idarubicin Combined with High-Dose Cytarabine Consolidation in Patients with Acute Myeloid Leukemia over 60 Years of Age in First Remission].

OBJECTIVE: To evaluate the efficacy and safety of idarubicin combined with high-dose cytarabine as a post-remission therapy for elderly patients with acute myeloid leukemia (AML). METHODS: From November 2017 to June 2021, 24 AML patients aged ≥60 years who were in complete remission for the first time were enrolled in consolidation chemotherapy with idarubicin (10 mg/m2 intravenously once for day 1) combined with high-dose cytarabine (1.5 g/m2 intravenously over 3 hours every 12 hours for day 1-3), and the efficacy and safety were observed. RESULTS: Among the 24 patients, there were 12 males and 12 females, the median age was 65 (60-78) years old, and the median follow-up time was 23.3 (2-42.7) months. By the end of the follow-up, 15 patients relapsed and 11 patients died. The median disease-free survival (DFS) was 9 months and there were 3 cases of 2-year DFS. The median overall survival (OS) was 16.2 months, and there were 4 cases of 2-year OS. In terms of safety, 6 patients had grade 1-2 non-hematological adverse reactions, 12 patients had grade 3-4 hematological adverse reactions, and a total of 6 patients developed infection after consolidation chemotherapy. Multivariate analysis showed that two induction cycles and high-risk cytogenetic abnormalities were the adverse factors of DFS and OS in elderly patients with AML in this study. CONCLUSION: For AML patients ≥60 years old in first complete remission, idarubicin combined with high-dose cytarabine as post-remission therapy has a better safety, but compared with other regimens does not improve the prognosis of elderly patients, which needs further exploration.