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.

OBJECTIVES: To investigate the neuroprotective effects of electroacupuncture (EA) preconditioning against cerebral ischemia-reperfusion injury (CIRI) mediated by gut microbiota modulation, Nrf2/HO-1 pathway activation, and ferroptosis suppression. METHODS: Adult male SD rats were divided into sham operation group, CIRI model group, and EA preconditioning group. In the latter two groups, rat models of CIRI were established by middle cerebral artery occlusion (MCAO), and in EA preconditioning group, EA was applied at Baihui (DU20) and Zusanli (ST36) for 3 days before modeling. Neurological deficits, cerebral infarction, and hippocampal pathology of the rats were evaluated using behavioral tests, TTC staining, and Nissl and HE staining, and the oxidative stress markers (MDA, ROS, and SOD), apoptosis/ferroptosis-related proteins (Bax, Bcl-2, GPX4, and SLC7A11), and changes in gut microbiota were analyzed. RESULTS: EA preconditioning significantly reduced neurological deficits, decreased infarct volume, promoted hippocampal neuronal survival, and improved structural integrity of the hippocampal neurons in MCAO rats. EA preconditioning also significantly lowered MDA and ROS and increased SOD levels, upregulated Bcl-2, GPX4, and SLC7A11 expressions, and downregulated Bax expression in the hippocampal tissue of the rats, causing also activation of Nrf2/HO-1 signaling and improvement of gut microbiota composition. CONCLUSIONS EA preconditioning alleviates CIRI in rats by suppressing ferroptosis and apoptosis, enhancing antioxidant defenses via activating Nrf2/HO-1 signaling, and regulating the gut-brain axis.
Animals ; Electroacupuncture ; NF-E2-Related Factor 2/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Reperfusion Injury/therapy* ; Ferroptosis ; Male ; Rats ; Brain Ischemia ; Gastrointestinal Microbiome ; Heme Oxygenase (Decyclizing)/metabolism* ; Brain/metabolism* ; Oxidative Stress ; Heme Oxygenase-1/metabolism* ; Apoptosis

A brain-computer interface (BCI) based on motor imagery (MI) provides additional control pathways by decoding the intentions of the brain. MI ability has great intra-individual variability, and the majority of MI-BCI systems are unable to adapt to this variability, leading to poor training effects. Therefore, prediction of MI ability is needed. In this study, we propose an MI ability predictor based on multi-frequency EEG features. To validate the performance of the predictor, a video-guided paradigm and a traditional MI paradigm are designed, and the predictor is applied to both paradigms. The results demonstrate that all subjects achieved > 85% prediction precision in both applications, with a maximum of 96%. This study indicates that the predictor can accurately predict the individuals' MI ability in different states, provide the scientific basis for personalized training, and enhance the effect of MI-BCI training.
Humans ; Imagination/physiology* ; Electroencephalography/methods* ; Brain-Computer Interfaces ; Male ; Female ; Adult ; Young Adult ; Brain/physiology* ; Movement/physiology* ; Motor Activity/physiology* ; Psychomotor Performance/physiology*

Objective To investigate the patterns of syndrome changes and their possible material basis in mouse models of chronic psychological stress during the modeling process.Methods A chronic unpredictable mild stress(CUMS)method was employed to prepare a model of chronic psychological stress in mice.After 2 weeks of modeling,Xiaoyao powder(XYS group)and Sini powder(SNS group)were administered concurrently with the modeling process.General conditions,behavioral,and biochemical indicators were compared between the modeling mice(M4 and M6 group)and the mice treated for 2 weeks(S4 and X4 group)and 4 weeks(S6 and X6 group)after chronic psychological stress.Results Compared with M4 group mice,body mass,total distance and central distance in the open field test,serum NE concentration,and gastric Ghrelin expression were increased in S4 group and X4 group mice,and sugar water preference rate and serum D-xylose concentration were increased in S4 group mice.Compared with X4 group mice,total distance in the open field test and serum D-xylose concentration were increased in the S4 group mice.Compared with M6 group mice,body mass,serum NE concentration,serum D-xylose concentration,and gastric Ghrelin expression were increased in group S6 and X6 group mice;sugar water preference rate,total distance in the open field test,and active avoidance counts in the shuttle box test were increased in X6 group mice,while their serum CORT concentration was decreased.Compared with S6 group mice,body mass,total distance in the open field test,serum D-xylose concentration,and gastric Ghrelin expression in X6 group mice were increased.Conclusions During the process of modeling chronic psychological stress in mice,the traditional Chinese medicine syndrome evolved from liver qi stagnation to liver qi stagnation with spleen deficiency.The biological bases of the syndrome changes may be the combined changes in serum CORT and NE concentrations and the decrease in gastric Ghrelin levels.

Objective:To investigate the expression of Artemin (ARTN) in malignant peripheral nerve sheath tumor (MPNST), its effect on the malignant behavior of MPNST cells, and its signaling pathway.Methods:Fifty-one MPNST paraffin embedded tissues through surgical resection at Tianjin Medical University Cancer Hospital from January 1995 to November 2011 were collected, the expression of the ARTN protein was detected by immunohistochemistry, and the relationship between the ARTN protein expression and the clinical pathological characteristics and prognosis were analyzed. In human MPNST cell lines ST-8814 (NF-1) and STS26T(sporadic), ARTN overexpression and low expression cell lines were constructed by transfecting ARTN overexpression plasmids and ARTN small interfering RNA (siRNA), respectively. The expression of ARTN mRNA was detected by real time quantitative polymerase chain reaction (RT-qPCR), the expression of the ARTN protein and Phosphoinositide 3-kinase(PI3K)/Akt signaling pathway related proteins were detected by Western blot. CCK-8 assay was used to detect cell proliferation ability, and cell invasion assay was used to detect cell invasion ability. The pathway proteins that interacted with ARTN were searched in the STRING database, and the functional pathways were clarified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The PI3K/Akt pathway specific inhibitor LY294002 was used to block the PI3K/Akt pathway of ST-8814 and STS26T cells to observe the changes in cell proliferation and invasion.Results:Among the 51 MPNST tissue specimens, 22 cases showed a high expression of the ARTN protein and 29 cases showed a low expression of the protein. Higher expressions of the ARTN protein was associated with larger tumor diameters and disease progression (recurrence or metastasis) (both P＜0.05). The median disease-free survival (DFS) of patients with a low expression of the ARTN protein was 26.2 months, and the median overall survival (OS) was 66.9 months. The median DFS and median OS of patients with a high expression of the ARTN protein were 10.7 months and 53.8 months, respectively. The log rank test results showed that the progression free survival rate of patients with a high expression of the ARTN protein was worse than that of patients with a low expression ( P=0.027), but the difference in overall survival rate between the two groups was not statistically significant ( P=0.790), which was also confirmed by Cox regression analysis. The CCK-8 assay results showed that after 48 hours of transfection, the absorbance ( A) values of ST-8814 and STS26T cells in the ARTN overexpression group were 1.35±0.01 and 1.10±0.02, respectively, which were higher than those in the empty plasmid control group (1.05±0.01 and 0.78±0.01, both P＜0.01), while the A values of ST-8814 and STS26T cells in the ARTN siRNA group were 0.35±0.01 and 0.61±0.01, respectively, which were lower than those in the control siRNA group (0.74±0.01 and 1.10±0.04, both P＜0.01). The results of cell invasion assay showed that the number of transmembrane cells in ST-8814 and STS26T cells overexpressing ARTN was (29.67±2.08) and (31.67±2.08), respectively, which were higher than those in the empty plasmid control group [(20.00±1.00) and (24.33±1.15), both P＜0.01]. The number of transmembrane cells in ST-8814 and STS26T cells in the ARTN siRNA group were (14.00±2.00) and (19.33±1.53), respectively, which were lower than those in the control siRNA group [(19.33±2.52) and (23.33±0.58), both P＜0.05].The KEGG results showed that ARTN is associated with multiple tumor signaling pathways, especially the PI3K/Akt signaling pathway. Western blot results showed that overexpression of ARTN upregulated the expression of p-PI3K and p-Akt proteins in ST-8814 and STS26T cells (both P＜0.01).After knocking down ARTN expression, the expression of p-PI3K and p-Akt proteins was significantly down regulated (both P＜0.01). LY294002 could significantly inhibit the effect of ARTN overexpression on ST-8814 and STS26T cells after blocking the PI3K/Akt pathway. The A values of ST-8814 and STS26T cells in the ARTN overexpression+LY294002 group were 1.09±0.06 and 0.82±0.01, respectively, which were lower than those in the ARTN overexpression group (1.50±0.01 and 1.29±0.01, respectively, both P＜0.01). The numbers of transmembrane cells in the cell invasion assay were 16.67±3.21 and 19.67±2.31, respectively, which were also lower than those in the ARTN overexpression group (29.67±2.08 and 31.67±2.08, respectively, both P＜0.01). Conclusions:In MPNST, a high expression of the ARTN protein was associated with larger tumor size, disease progression, and worse DFS. ARTN promotes the proliferation and invasion of MPNST cells through the PI3K/Akt signaling pathway.

AIM:To evaluate the effects of liposo-mal bupivacaine for interscalene brachial plexus block on postoperative analgesia and diaphragmat-ic function in patients undergoing arthroscopic ro-tator cuff repair surgery based on a randomized controlled trial.METHODS:Forty patients who scheduled to undergo arthroscopic rotator cuff re-pair surgery,regardless of gender,aged 18 to 65 years,ASA grade Ⅰ or Ⅱ were selected from October 2023 to February 2024.The patients were random-ly divided into bupivacaine liposome group(group LB)and the levobupivacaine group(group BV),with 20 cases in each group.Patients in both groups re-ceived an ultrasound-guided interscalene brachial plexus block,15 mL mixed liquids(bupivacaine lipo-some 10 mL+0.5％levobupivacaine 10 mL)were in-jected into the level of C5-C6 nerve roots and 5 mL onto the surface of prevertebral fascia in the LB group,and same volume of 0.375％levobupiva-caine were injected at the same sites in the BV group respectively.Standardized general anesthe-sia and standardized postoperative analgesia were followed.The primary outcome measures included 48 h rest/motor numerical rating scale(NRS)scores after surgery and the incidence of hemidiaphrag-matic paralysis(HDP)after block.The secondary outcome measures included rest/motor NRS scores at other time points after surgery,pulse oxygen sat-uration(SpO2)30 min after block,duration of sen-sory and motor block,number of analgesic pump presses,time of first postoperative used of opioid drugs and opioid consumption,use of additional analgesics in the wards,satisfaction with analgesia,and the occurrence of perioperative adverse ef-fects and neurological complications.RESULTS:Compared with group BV,patients in LB group showed lower rest NRS scores at 48 h postopera-tion(P＜0.05)and higher incidence of HDP at 24 h after block(45％vs.5.3％,P＜0.05).However,there was no significant difference in motor NRS scores at 48 h,HDP incidence at 30 min and 6 h after block between the two groups(P＞0.05).Both groups showed a decrease in SpO2 after block com-pared to before block(P＜0.05).Compared with BV group,patients in LB group had a significantly lon-ger duration of sensory and motor block(P＜0.01),fewer effective presses with the analgesic pump(P＜0.01),delay in first opioid use and less opioid con-sumption(P＜0.05),higher level of satisfaction with analgesia(P＜0.01),and a lower rate of use of addi-tional analgesics in the ward(P＜0.05).There was no statistically significant difference in the total in-traoperative remifentanil consumption,incidence of perioperative adverse reactions and neurological complication between the two groups(P＞0.05).CONCLUSION:Compared with using levobupiva-caine alone,the addition of liposomal bupivacaine for interscalene brachial plexus block in arthroscop-ic rotator cuff repair can reduce postoperative NRS scores,decrease postoperative opioid dosage and significantly prolong blockduration,but can easily lead to longer duration of HDP in patients.

The receptors of Newcastle disease virus(NDV)are sialic acid receptors that mainly in-clude neu5ac-α-2,3gal-β-1,4Glc(SAα2,3Gal)and neu5ac-2-s-α-2,6Gal10Me(SAα2,6Gal).The distribution and abundance of the two receptors in host cells have important effects on virus sus-ceptibility and intracellular proliferation.In order to further explore the effects of sialic acid recep-tors on susceptibility and proliferation characteristics of NDV different strains,the expression lev-els of SAα2,3Gal and SAα2,6Gal receptors on BHK-21 cell membrane were adjusted by overex-pression and RNAi assays,and the TCID50 values were determined after different BHK-21 cells were inoculated with NDV strains Ⅰ and LaSota.The results suggested that NDV strain LaSota preferentially binds to SAα2,6Gal and strain Ⅰ selectively binds to SAα2,3Gal receptor.Further-more,the viral titers of NDV strains LaSota and Ⅰ in cell culture were positively correlated with the expression levels of SAα2,6Gal and SAα2,3Gal receptors on host cell membrane respectively.In conclusion,our studies provide an understanding of the relationship between infectivity of NDV different strains and receptor types of host cell,and provide a method to increase viral titer of NDV for cell-based vaccine production.

Objective:To explore the design requirements of nurses in the Neurointensive Care Unit (NICU) for the closed-eye pupil monitoring system, providing reference for the refinement and upgrade of the system.Methods:This study was descriptive and qualitative. From December 2024 to February 2025, 15 NICU nurses from Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, were selected using purposive sampling for semi-structured interviews. Content analysis method was used to analyze data and extract key themes.Results:NICU nurses' design requirements for closed-eye pupil monitoring system were categorized into six themes and 18 sub-themes, namely physical characteristics requirements (strong device stability, compact and lightweight design), comfort and safety requirements (wear comfort and safety, prevention of light source thermal injury, convenient disinfection and infection control, assisting eyelid closure), functional requirements (automated monitoring and data collection, intelligent alarm and alert mechanisms), operational requirements (ready-to-use, easy to wear, simple operation), data monitoring requirements (data storage and integrity, data visualization and timeliness, data analysis and prediction, system integration and data management), and extended functional requirements (consciousness state monitoring, fundus lesion examination, vision and visual field screening) .Conclusions:NICU nurses' design requirements for the closed-eye pupil monitoring system are multidimensional and multi-level. System developers should continuously optimize system design based on the actual needs of nurses.

Objective This study aimed to investigate the value of PET/CT radiomics combined with machine learning in differentia-ting primary central nervous system lymphoma(PCNSL)from brain metastases(BM).Methods Sixty-nine patients with 127 lesions(including 43 PCNSL lesions and 84 BM lesions)who attended the Department of Nuclear Medicine of Lanzhou University Second Hospi-tal from January 2019 to November 2024 were selected and divided into a training set(n=88)and a validation set(n=39)in a 7∶3 rati-o.Radiomics features of PET and CT were extracted using the 3D slicer,and feature dimensionality reduction was performed using least absolute shrinkage and selection operator(LASSO)regression combined with 5-fold cross-validation to construct three classical machine learning models-Logistic regression(LR),decision tree(DT),and support vector machine(SVM),and the diagnostic efficacy of each model was evaluated using receiver operating characteristic(ROC)curves and confusion matrices.Results The SVM model based on PET imaging performed best in the validation set[area under the curve(AUC)=0.917,sensitivity=84.6％,specificity=92.3％]and was significantly better than the CT model(AUC=0.787,sensitivity=73.1％,specificity=76.9％).Conclusion The support vector machine model constructed based on PET radiomics metabolic features demonstrated high diagnostic value in the preoperative differentia-tion between PCNSL and BM,showing potential for clinical application as a non-invasive auxiliary diagnostic tool.

Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.