Intravascular large B-cell lymphoma (IVLBCL), a rare subtype of non-Hodgkin lymphoma, is classified as an independent subtype of extranodal diffuse large B-cell lymphoma (DLBCL) in the 2008 World Health Organization (WHO) Classification (Turner et al., 2010). The 5th edition of the World Health Organization (WHO 2022) classification of hematolymphoid tumors retains this subtype (Alaggio et al., 2022). IVLBCL, which is characterized by neoplastic lymphocyte proliferation within the lumen of small blood vessels, tends to invade organs, such as the nervous system, skin, bone marrow (BM), and lung (D'Angelo et al., 2019; Satoh et al., 2019; Vásquez et al., 2019; Fukami et al., 2020).
Humans ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Vascular Neoplasms/therapy*

Metabolic dysfunction-associated steatohepatitis (MASH), a severe type of metabolic dysfunction-associated steatotic liver disease (MASLD), is a leading etiology of end-stage liver disease worldwide, posing significant health and economic burdens. microRNA-320 (miR-320), a ubiquitously expressed and evolutionarily conserved miRNA, has been reported to regulate lipid metabolism; however, whether and how miR-320 affects MASH development remains unclear. By performing miR-320 in situ hybridization with RNAscope, we observed a notable downregulation of miR-320 in hepatocytes during MASH, correlating with disease severity. Most importantly, miR-320 downregulation in hepatocytes exacerbated MASH progression as demonstrated that hepatocyte-specific miR-320 deficient mice were more susceptible to high-fat, high-fructose, high-cholesterol diet (HFHC) or choline-deficient, amino acid-defined, high-fat diet (CDAHFD)-induced MASH compared with control littermates. Conversely, restoration of miR-320 in hepatocytes ameliorated MASH-related steatosis and fibrosis by injection of adeno-associated virus 8 (AAV8) carrying miR-320 in different types of diet-induced MASH models. Mechanistic studies revealed that miR-320 specifically regulated fibroblast growth factor 1 (FGF1) production in hepatocytes by inhibiting regulator factor X1 (RFX1) expression. Notably, knockdown of Rfx1 in hepatocytes mitigated MASH by enhancing FGF1-mediated AMPK activation. Our findings underscore the therapeutic potential of hepatic miR-320 supplementation in MASH treatment by inhibiting RFX1-mediated FGF1 suppression.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Objective The volume and cortical thickness of gray matter in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) were compared and analyzed by voxel⁃based morphometry (VBM) and surface⁃based morphometry (SBM), and the differences in the structural changes of gray matter in the two diseases were discussed. Methods A total of 21 MS patients, 16 NMO patients and 19 healthy controls were scanned by routine MRI sequence. The data were processed and analyzed by VBM and SBM method based on the statistical parameter tool SPM12 of Matlab2014a platform and the small tool CAT12 under SPM12. Results Compared with the normal control group (NC), after Gaussian random field (GRF) correction, the gray matter volume in MS group was significantly reduced in left superior occipital, left cuneus, left calcarine, left precuneus, left postcentral, left central paracentral lobule, right cuneus, left middle frontal, left superior frontal and left superior medial frontal (P<0. 05). After family wise error (FWE) correction, the thickness of left paracentral, left superiorfrontal and left precuneus cortex in MS group was significantly reduced (P<0. 05). Compared with the NC group, after GRF correction, the gray matter volume in the left postcentral, left precentral, left inferior parietal, right precentral and right middle frontal in NMO group was significantly increased (P<0. 05). In NMO group, the volume of gray matter in left middle occipital, left superior occipital, left inferior temporal, right middle occipital, left superior frontal orbital, right middle cingulum, left anterior cingulum, right angular and left precuneus were significantly decreased (P<0. 05). Brain regions showed no significant differences in cortical thickness between NMO groups after FWE correction. Compared with the NMO group, after GRF correction, the gray matter volume in the right fusiform and right middle frontal in MS group was increased significantly(P<0. 05). In MS group, the gray matter volume of left thalamus, left pallidum, left precentral, left middle frontal, left middle temporal, right pallidum, left inferior parietal and right superior parietal were significantly decreased (P<0. 05). After FWE correction, the thickness of left inferiorparietal, left superiorparietal, left supramarginal, left paracentral, left superiorfrontal and left precuneus cortex in MS group decreased significantly (P<0. 05). Conclusion The atrophy of brain gray matter structure in MS patients mainly involves the left parietal region, while NMO patients are not sensitive to the change of brain gray matter structure. The significant difference in brain gray matter volume between MS patients and NMO patients is mainly located in the deep cerebral nucleus mass.

Objective:To investigate the association between plasma anti-Müllerian hormone(AMH) levels and ischemic stroke.Methods:In this case-control study, 93 ischemic stroke patients were randomly selected as the case group from a study on the prevention and treatment of metabolic syndrome, which was conducted in 2018-2019 in Changshu, Jiangsu Province, while 372 nonischemic stroke patients were selected as the control group according to the principle of 1∶4 matching.An enzyme-linked immunosorbent assay was used to measure plasma AMH levels.The conditional logistic regression model and restricted cubic spline were used to analyze the relationship between AMH levels and ischemic stroke.Results:A total of 465 subjects with an average age of (68.7±7.4)years were included in this study, of whom 215(46.2%)were men and 250(53.8%)were women.According to our conditional Logistic regression analysis, the risk of ischemic stroke was reduced by 44% for every unit increase in the log-AMH level( OR=0.56, 95% CI: 0.37-0.85)in the overall population after multivariate adjustment.Compared with the tertile with the lowest AMH level, the risk of ischemic stroke in the tertile with the highest AMH level decreased significantly( OR=0.37, 95% CI: 0.19-0.69). When subgrouped by sex, the tertiles with the highest AMH levels were associated with a 66% lower risk of ischemic stroke in men( OR=0.34, 95% CI: 0.13-0.88)and a 64% lower risk of ischemic stroke in women( OR=0.36, 95% CI: 0.15-0.87), compared with the tertiles with the lowest AMH levels.The results of restricted cubic spline analysis showed that there was a linear dose-response relationship between plasma AMH levels and ischemic stroke both in the general population and in male or female population( Pvalues for linear trends were 0.0002, 0.008 and 0.007, respectively). Conclusions:Higher plasma AMH levels decrease the risk of ischemic stroke with a dose-response pattern.

AIM To study the chemical constituents from the twigs of Aglaia perviridis Hiern and their total antioxidant and neuroprotective activities.METHODS The 95%ethanol extract from the twigs of A.perviridis were isolated and purified by silica gel,ODS and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant and neuroprotective activities were evaluated by T-AOC kit and MTT assay,respectively.RESULTS Twenty-one compounds were isolated and identified as 3-epicotillol(1),syringic acid(2),palmitic acid(3),di-N-pentyl phthalate(4),ethyl-4-hydroxyphenylacetate(5),7-hydroxy-6-methoxycoumarin(6),1-octanol(7),p-hydroxyphenylacetic acid(8),(+)-syringaresinol-4-O-β-D-glucopyranoside(9),(+)-episyring-4-O-β-D-glucopyranoside(10),methy-4-hydroxyphenylacetate(11),koaburaside(12),byzantionoside B(13),quercetin 3-O-α-L-rhamnopyranoside(14),(2R,3R)-(+)-glucodistylin(15),(2S,3S)-(-)-glucodistylin(16),(+)-lyoniresinol-3α-O-β-D-glucopyranoside(17),(+)-isolariciresinol-9'-O-β-D-glucopyranosidede(18),(-)-lyoniresinol-3α-O-β-D-glucopyranoside(19),phlorizin(20),β-sitosterol(21).The total antioxidant capacity of compounds2,9-10,14-20 was 10.300-38.367 U/(mmol·L-1).The neuroprotective effects of compounds 2,10 and 17 were concentration-dependent,and the optimal concentrations of compounds 9 and 15 were 50,100 μmol/L,respectively.CONCLUSION Compounds 1-20 are isolated from this plant for the first time.Compounds 2,9-10,14-20 have strong total antioxidant activities.Compounds 2,9-10,15,17 have neuroprotective activities.

Objective:To retrospectively analyze the clinical characteristics and prognosis of 85 newly diagnosed patients with follicular lymphoma (FL), as well as the prognostic value of comprehensive geriatric assessment (CGA) in patients with FL aged ≥ 60 years old.Methods:The clinical data and prognosis of 85 newly diagnosed FL patients admitted from August 2011 to June 2022 were collected. The clinical features, laboratory indicators, therapeutic efficacy, survival and prognostic factors of patients were statistically analyzed, and the prognosis of patients was stratified using various geriatric assessment tools.Results:① The patients with FL were mostly middle-aged and older, with a median age of 59 (20-87) years, including 41 patients (48.2%) aged ≥60 years. The ratio of male to female was 1∶1.36. Overall, 77.6% of the patients were diagnosed with Ann Arbor stage Ⅲ-Ⅳ, and 17 cases (20.0%) were accompanied by B symptoms. Bone marrow involvement was the most common (34.1%). ②Overall, 71 patients received immunochemotherapy. The overall response rate was 86.6%, and the complete recovery rate was 47.1% of 68 evaluated patients. Disease progression or relapse in the first 2 years was observed in 23.9% of the patient. Overall, 14.1% of the patients died during follow-up. ③Of the 56 patients receiving R-CHOP-like therapies, the 3-year and 5-year progression-free survival (PFS) rates were 85.2% and 72.8%, respectively, and the 3-year and 5-year overall survival (OS) rates were 95.9% and 88.8%, respectively. The univariate analysis showed that age ≥60 years old ( HR=3.430, 95% CI 1.256-9.371, P=0.016), B symptoms ( HR=5.030, 95% CI 1.903-13.294, P=0.016), Prognostic Nutritional Index (PNI) <45.25 ( HR=3.478, 95% CI 1.299-9.310, P=0.013), Follicular Lymphoma International Prognostic Index (FLIPI) high-risk ( HR=2.918, 95% CI 1.074-7.928, P=0.036), and PRIMA-prognostic index (PRIMA-PI) high-risk ( HR=2.745, 95% CI 1.057-7.129, P=0.038) significantly predicted PFS. Moreover, age ≥60 years old and B symptoms were independent risk factors for PFS. Progression of disease within 24 months (POD24) significantly predicted OS in the univariate analysis. Conclusions:FL is more common among middle-aged and older women. Age, B symptoms, PNI score, FLIPI high-risk, PRIMA-PI high-risk, and POD24 influenced PFS and OS. The CGA can be used for treatment selection and risk prognostication in older patients with FL.

Polatuzumab vedotin (Pola) is a novel antibody-drug conjugate targeting CD79b, which has been shown to be effective in treating newly diagnosed and relapsed/refractory diffuse large B cell lymphoma (DLBCL) during clinical trials. This study aims to conduct a retrospective analysis of the clinical characteristics, diagnosis, and treatment of a patient with refractory secondary central nervous system lymphoma at Beijing Hospital, alongside a review of relevant literature. This study included a 79-year-old female patient who was diagnosed with DLBCL affecting the ilium, sacrum, spinal cord, and nerve roots and had an IPI score of 5 and a high-risk score according to MSKCC. She showed a geriatric comprehensive assessment (IACA) score of 2, which was categorized under the unfit group. Her initial treatment comprised chemo-free therapy and radiotherapy, followed by progression. In the second-line treatment, a Pola-based regimen was applied, and the patient achieved a complete response, suggesting that this regimen may be a therapeutic option for patients with DLBCL involving the central nervous system.

Purpose: This study aimed to analyze the expression and prognosis of SRY-box transcription factor 11 (SOX11) in neuroblastoma (NB), as well as the biological function and potential regulatory mechanism of SOX11 in NB. Methods: Public RNA sequencing was used to detect the expression level of SOX11. The Kaplan-Meier curve and hazard ratios (HR) were used to determine the prognostic value of SOX11 in NB. Functional analyses were performed using CCK8, wound healing assay, and transwell invasion assay. Finally, the potential target genes of SOX11 were predicted by Harmonizonme (Ma'ayan Laboratory) and Cistrome Data Browser (Cistrome Project) database to explore the potential molecular mechanism of SOX11 in NB. Results: Compared with normal adrenal tissue, the expression of SOX11 in NB tissue was significantly upregulated. The Kaplan-Meier curve showed that high expression of SOX11 was associated with poor prognosis in children with NB (HR, 1.719; P = 0.049). SOX11 knockdown suppressed the migration capacity of SK-N-SH cells but did not affect proliferation and invasion capacity. Enhancer of zeste homolog 2 (EZH2) may be a potential downstream target gene for the transcription factor SOX11 to play a role in NB. Conclusion The transcription factor SOX11 was significantly upregulated in NB. SOX11 knockdown suppressed the migration capacity of NB cell SK-N-SH. SOX11 may promote the progression of NB by targeting EZH2.

Background: Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified. Methods: In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed. Results: In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation. Conclusion Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.