OBJECTIVE To explore the ameliorative effect and potential mechanism of vitexin on inflammation in ulcerative colitis （UC） mice. METHODS The UC mice model was established by continuous administration of 3% dextran sulfate sodium solution for 5 days. Mice with successful modeling were randomly divided into UC group， vitexin low- and high-dose groups （vitexin-L and vitexin-H groups， 40， 80 mg/kg）， mesalazine group （400 mg/kg）， and vitexin-H+recombinant Jagged canonical Notch ligand 1 （rJagged-1） group （vitexin-H+rJagged-1 group， 80 mg/kg vitexin+1 mg/kg rJagged-1）， with 12 mice in each group. Another 12 normal mice were used as the control （CK） group. Mice in each group were administered the corresponding drugs or the corresponding drugs and normal saline by gavage and intraperitoneal injection once daily for 7 consecutive days. General conditions were observed during the experiment. At 24 h after the last administration， the disease activity index （DAI） score was evaluated. Colonic histopathological morphology was observed and scored. Macrophage polarization levels in the spleen and colon tissues were measured. The protein expressions of interleukin-6 （IL-6）， IL-10， tumor necrosis factor-α （TNF-α）， transforming growth factor-β 1 （TGF-β 1 ）， Jagged-1， Notch1 and Notch intracellular domain （NICD） in colonic tissues were determined. RESULTS Compared with the UC group， the symptoms （reduced food and water intake， dull fur， etc.） and pathological changes （epithelial cell shedding， inflammatory cell infiltration， etc.） were significantly improved in the vitexin-L， vitexin-H and mesalazine groups. DAI scores， colonic histopathological scores， M1 macrophage contents in spleen tissue， M1/M2 macrophage ratios， M1 macrophage proportions in colon tissue， and protein expressions of IL-6， TNF-α， Jagged-1， Notch1 and NICD in colon tissue were significantly decreased （ P ＜0.05）. Meanwhile， the M2 macrophage contents in spleen tissue， M2 macrophage proportions in colon tissue， and protein expressions of IL-10 and TGF-β 1 in colon tissue were significantly increased （ P ＜0.05）. Moreover， the improvement effects in the vitexin-H and mesalazine groups were significantly superior to those in the vitexin-L group （ P ＜0.05）. Compared with the vitexin-H group， the above symptoms and pathological changes were aggravated， and all quantitative indicators were significantly reversed in the vitexin-H+rJagged-1 group （ P ＜0.05）. CONCLUSIONS Vitexin can ameliorate the inflammation of UC mice， which is associated with its inhibition of the Jagged-1/Notch1 pathway and regulation of macrophage polarization （inhibition of M1-type polarization and promotion of M2-type polarization）.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Objective To construct and evaluate a prognostic model for clear cell renal cell carcinoma(ccRCC)based on preoperative lipid ratios, cM0(i+)staging, and other clinical characteristics, so as to provide a precise tool for clinical prognosis assessment. Methods A retrospective analysis was conducted on the clinical data of 215 ccRCC patients treated in our hospital during May 2014 and May 2023. Lipid ratios were calculated using preoperative lipid data, and patients were divided into cM0(i+)stage or cM0 stage according to postoperative circulating tumor cells(CTCs)test results. The optimal lipid ratio and cutoff value were selected using receiver operating characteristic(ROC)curves and the X-tile method. Patients were subdivided into three groups based on the level of the low-density lipoprotein cholesterol to non-low-density lipoprotein cholesterol ratio(LNLR)and cM0(i+)staging:Group A [LNLR＞1.68 and diagnosed with cM0(i+)], Group B [LNLR＞1.68 or diagnosed with cM0(i+)], and Group C(LNLR ≤1.68 and diagnosed with cM0). Kaplan-Meier survival analysis was used to plot survival curves for patients in different groups. The log-rank test was employed to compare differences in recurrence-free survival(RFS)among the subgroups. Multivariate Cox regression analysis was conducted to identify the independent risk factors influencing RFS, and a nomogram prediction model was constructed based on these results. The predictive performance of the model was validated using ROC curves, calibration curves, and decision curves. Results ROC curves were plotted for lipid markers, and LNLR was identified as the most predictive for RFS. Its optimal cutoff point was 1. 68. Patients in Group A experienced a significantly shorter postoperative RFS. Multivariate Cox regression analysis identified preoperative LNLR, cM0(i+)staging, pathological grade, and stage as independent risk factors for RFS. A nomogram model was constructed based on these risk factors. The area under the ROC curve(AUC)for 1-, 3-, and 5-year RFS was 0.896(95% CI:0.8121-0.9627), 0.890(95%CI:0.7879-0.9641), and 0.870(95%CI:0.7697-0.9526), indicating good discriminatory ability and predictive performance. Calibration plots demonstrated good agreement between predicted and actual outcomes. Clinical decision curve analysis showed high clinical net benefit. Conclusion Preoperative LNLR level is an independent risk factor for RFS in ccRCC patients. The prognostic prediction model based on LNLR, cM0(i+)staging, patient pathological grade, and staging demonstrates good predictive performance for RFS and holds potential clinical application value.

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

OBJECTIVE: To analyze the B_el subtype gene mutation and its genetic mechanism in a family line. METHODS: ABO blood groups were identified by serologic tests. ABO genotyping was performed by polymerase chain reaction with sequence-specific primer (PCR-SSP). Sanger sequencing was performed on exons 1-7 of the ABO gene, the flanking intronic region, and exon 7 of the single strand of the gene confirmed the mutation site location. Missense3D software was used to predict the protein structure alteration caused by this mutation. RESULTS: Conventional serologic tests failed to detect erythrocyte B antigen in the proband and her three family members, and only trace amounts of B antigen expression could be detected by the absorption-dispersal test. DNA analysis showed that, on the basis of the normal ABO gene, there was a G>T substitution in the position of exon 7, position 803, which resulted in the change of amino acid 268 from Gly to Val. Further single-stranded sequencing analysis showed that the mutation site was located in the B gene. CONCLUSION In this family line, the proband, her father, her son, and her daughter all have reduced B type glycosyltransferase activity due to the new point mutation (c.803G>T) in exon 7 of the B gene, and the B antigen can only be detected by the absorption-dispersal method, and the point mutation can be stably inherited by offspring.
Point Mutation ; Alleles ; ABO Blood-Group System/genetics* ; Exons ; Introns ; Genotype ; Humans ; Male ; Female ; Glycosyltransferases/genetics*

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

To address the challenges faced by current brain midline segmentation techniques, such as insufficient accuracy and poor segmentation continuity, this paper proposes a deep learning network model based on a two-stage framework. On the first stage of the model, prior knowledge of the feature consistency of adjacent brain midline slices under normal and pathological conditions is utilized. Associated midline slices are selected through slice similarity analysis, and a novel feature weighting strategy is adopted to collaboratively fuse the overall change characteristics and spatial information of these associated slices, thereby enhancing the feature representation of the brain midline in the intracranial region. On the second stage, the optimal path search strategy for the brain midline is employed based on the network output probability map, which effectively addresses the problem of discontinuous midline segmentation. The method proposed in this paper achieved satisfactory results on the CQ500 dataset provided by the Center for Advanced Research in Imaging, Neurosciences and Genomics, New Delhi, India. The Dice similarity coefficient (DSC), Hausdorff distance (HD), average symmetric surface distance (ASSD), and normalized surface Dice (NSD) were 67.38 ± 10.49, 24.22 ± 24.84, 1.33 ± 1.83, and 0.82 ± 0.09, respectively. The experimental results demonstrate that the proposed method can fully utilize the prior knowledge of medical images to effectively achieve accurate segmentation of the brain midline, providing valuable assistance for subsequent identification of the brain midline by clinicians.
Humans ; Brain/diagnostic imaging* ; Deep Learning ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Magnetic Resonance Imaging/methods* ; Neural Networks, Computer