JMJD1C (Jumonji Domain Containing 1C), a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with different genetic mutations, representing a therapeutic opportunity with broad application. Yet how JMJD1C regulates the leukemic programs of various AML cells is largely unexplored. Here we show that JMJD1C interacts with the master hematopoietic transcription factor RUNX1, which thereby recruits JMJD1C to the genome to facilitate a RUNX1-driven transcriptional program that supports leukemic cell survival. The underlying mechanism hinges on the long N-terminal disordered region of JMJD1C, which harbors two inseparable abilities: condensate formation and direct interaction with RUNX1. This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias.
Core Binding Factor Alpha 2 Subunit/genetics* ; Humans ; Leukemia, Myeloid, Acute/pathology* ; Jumonji Domain-Containing Histone Demethylases/chemistry* ; Gene Expression Regulation, Leukemic ; Oxidoreductases, N-Demethylating/genetics* ; Cell Line, Tumor

Objective:To study on anti-osteoporosis effect of different extracts of Polygoni Multiflori Radix Praeparata on zebrafish.Methods:Three kinds extracts of Polygoni Multiflori Radix Praeparata, anthraquinone and stilbene glycosides and the removal of anthraquinone and stilbene glycosides were prepared. Prednisolone was used to construct the osteoporosis model of young zebrafish. Normal control group, model group, disodium etidronate group and low-, medium- and high-dosage groups of different extracts of Polygoni Multiflori Radix Praeparata were set up. Alizarin red staining was used to investigate the mineralized skull area and bone density of juvenile zebrafish in each group. Alkaline phosphatase (AKP) and tartrate-resistant acid phosphatase (TRACP) kits were used to detect the activity of osteoblast and osteoclast enzymes in zebra larvae. The qRT PCR method was used to detect the mRNA expressions of osteoporosis related genes Runx2b, col1a2, sparc, and vdrb in each group of zebrafish.Results:Compared with model group, the skull mineralized area and bone mineral density in different extracts of Polygoni Multiflori Radix Praeparata significantly increased ( P<0.01). Polygoni Multiflori Radix Praeparata, anthraquinone and stilbene glycosides and the removal of anthraquinone and stilbene glycosides (medium- and high-dosage) could significantly increase the AKP activity of zebrafish ( P<0.01), and lower the TRAP activity of zebrafish ( P<0.01); the mRNA expression levels of Runx2b, col1a2, sparc and vdrb in juvenile zebrafish osteoporosis model were significantly up-regulated by different extracts of Polygoni Multiflori Radix Praeparata. ( P<0.01). Conclusion:Polygoni Multiflori Radix Praeparata, Anthraquinone and stilbene glycosides and the removal of anthraquinone and stilbene glycosides show better anti-osteoporosis effects. The comparison of the efficacy of three extracts from Polygonum multiflorum shows that in addition to anthraquinone and stilbene glycosides, other chemical components of Polygonum multiflorum have anti-osteoporosis effects.

BACKGROUND:The combination of good biomechanical properties,controlled drug release and multi-functionality of core-shell structured nanofibers is receiving more and more attention,which also makes them promising for a wide range of applications in the field of oral tissue regeneration. OBJECTIVE:To summarize the preparation,drug loading and release mechanisms of core-shell structured nanofibers and their application in the regenerative repair of oral tissues. METHODS:A computer search of the literature collected in CNKI and PubMed from January 2000 to November 2022 was applied,and the search terms in English and Chinese were"electrospinning,core-shell structures,drug delivery systems,jaw bone regeneration,cartilage regeneration,periodontal tissue regeneration". RESULTS AND CONCLUSION:(1)There are various methods for the preparation of core-shell structured nanofibers,but the coaxial and emulsion methods of electrostatic spinning have unique advantages such as simple operation,diverse material selection and good biocompatibility.(2)Core-shell structured nanofibers can be used as bacteriostatic agents,carriers of different types of drugs,and scaffolds for cell adhesion,providing new therapeutic options for oral tissue regeneration.(3)Controlled degradation and drug release rate of core-shell structured nanofibers can better adapt to the healing process of oral tissue defect repair and achieve ideal tissue regeneration.

【Objective】 To statistically analyze the relationship between homologous recombination repair deficiency (HRD) score and clinicopathological characteristics, genomic mutations in patients with high-risk and metastatic hormone-sensitive prostate cancer (mHSPC) and the prognostic predictive value in mHSPC. 【Methods】 A total of 127 patients diagnosed with high-risk prostate cancer and mHSPC, treated at the Department of Urology of Chinese PLA General Hospital during Dec.2021 and Nov.2023 were enrolled.Homologous recombination repair (HRR) gene sequencing was performed, and the genomic scar score (GSS) algorithm were conducted to calculate the HRD score.The relationship between HRD scores and clinicopathological features, genomic alterations, and prognosis were analyzed. 【Results】 The median HRD score was 1.6(0.8, 5.2), 30(23.6%) patients’ HRD scores ≥10, and 11(8.7%) patients’ HRD scores ≥20.Clinicopathological features, including ISUP classification ≥4 (P=0.044) and metastatic status (P=0.008) were associated with high HRD score.Patients with mutations in the BRCA, TP53 and MYC systems had significantly higher HRD score than those with wild-type genes (P<0.05).In mHSPC, the risk of biochemical recurrence was 12.836 times higher in patients with HRD score ≥20 than in those with <20 [OR:12.836 (1.332-124.623), P=0.028]. 【Conclusion】 Baseline HRD score was lower in patients with high-risk prostate cancer and mHSPC.Patients with high HRD score may have higher histological grading (ISUP≥4) and later clinical stage.Further investigation is needed to determine the threshold of HRD scores as biochemical markers suggestive of a poor prognosis.

A composite nystagmus classification framework enhanced by dual attention mechanism is proposed to address the problem that the existing researches only identify whether nystagmus occurs in a horizontal,vertical,or axial direction,but fail to consider the issue of composite nystagmus composed of multiple directions with various intensities in clinical practice.A spatiotemporal concentration algorithm for nystagmus videos is presented,and it combines convolutional neural networks and Hough transform to remove interference from invalid frames and regions and to improve the quality of nystagmus videos.Then,a dense optical flow algorithm is used to extract the optical flow field of eye movement.Finally,a composite nystagmus classification network based on dual attention mechanism enhancement is constructed.An improved efficient channel attention module is used to effectively obtain the direction and intensity of nystagmus in different channels of the optical flow map;and a temporal attention module is added at the end of the bidirectional long short-term memory network to achieve significant expression of classification results based on different temporal features.On the nystagmus dataset provided by the cooperating hospital,the proposed method has an accuracy rate of 83.17%for composite nystagmus classification,and achieved accuracy rates of 91.03%,89.74%,and 86.05%for individual horizontal,vertical,and axial nystagmus classifications.The proposed method realizes the intelligent classification of composite nystagmus and is valuable in clinic.

Objective:To explore the correlation between mechanical complications and paraspinal muscle degeneration following posterior single-segment osteotomy corrective surgery for chronic osteoporotic vertebral compression fractures (OVCF).Methods:A retrospective analysis was conducted on 80 patients who underwent surgery between January 2008 and January 2021 at Peking University Third Hospital. These patients, who developed kyphotic deformity following OVCF, included 17 males and 63 females with a mean age of 63.21±8.07 years (range, 47-77 years). Postoperative mechanical complications included proximal junctional kyphosis (PJK), screw loosening, adjacent segment degeneration (ASD), and distal junctional kyphosis or failure. Patients were compared based on the occurrence of mechanical complications in relation to fat infiltration (FI), relative gross cross-sectional area (rGCSA), and relative functional cross-sectional area (rFCSA) of the paraspinal muscles. Binary logistic regression analysis was used to identify risk factors for postoperative complications.Results:Among the 80 patients, 19 developed PJK, while 61 did not. The PJK group exhibited significantly higher paraspinal muscle FI (0.44±0.05) compared to the non-PJK group (0.38±0.10, P<0.05). Screw loosening occurred in 7 cases, with 73 cases remaining stable. Those with screw loosening demonstrated higher paraspinal muscle FI (0.47±0.05) than those without (0.38±0.09, P<0.05). Thirty patients experienced ASD, while 50 did not. The ASD group had higher paraspinal muscle FI (0.45±0.07) and lower rFCSA (0.09±0.03) compared to the non-ASD group (0.36±0.10 and 0.13±0.06, respectively, P<0.05). Logistic regression analysis indicated that paraspinal muscle FI and rFCSA were not independent risk factors for developing ASD. Twenty-three patients experienced distal junctional kyphosis or failure, while 57 did not; those with complications exhibited higher paraspinal muscle FI (0.48±0.08) and lower rGCSA (0.16±0.04) and rFCSA (0.09±0.03) compared to those without complications (0.37±0.09, 0.20±0.09, and 0.13±0.06, respectively, P<0.05). Logistic regression analysis suggested that paraspinal muscle FI, rGCSA, and rFCSA were not independent risk factors for developing distal junctional kyphosis or failure. Conclusion:Mechanical complications following corrective surgery for chronic OVCF-related kyphosis may be associated with increased paraspinal muscle FI. Additionally, the occurrence of ASD and distal junctional kyphosis or failure may correlate with reduced paraspinal muscle rFCSA

Objective:To investigate whether heat shock protein 90 (HSP90) participates in the necroptosis of C57BL/6 mouse neurons and spatial memory impairment induced by Aluminum maltol [Al (mal) 3] through RIP1/RIP3/MLKL pathway. Methods:In March 2022, Thirty-two C57 mice were randomly divided into control group, Low dose group, a medium dose group, and a high-dose group, with 8 mice in each group, and injected intraperitoneally with physiological saline, 20, 40, and 80, respectivelyμmol/kgAl (mal) 3 was administered, it was injected 5 days a week and discontinued 2 days for 60 days. Morris water maze test was used to test the spatial learning and memory ability of mice. Nissl staining was used to observe the pathological changes of brain tissue. The protein expression levels of RIP1, RIP3, MLKL and HSP90 in hippocampus were determined by Western blotting. Results:In the water maze experiment, compared with the control group, the number of mice crossing the platform decreased in each dose group, the difference was statistically significant ( H=9.50, P=0.023), and the number of mice crossing the platform was statistically significant among each dose group ( P <0.05). Compared with the control group, the number of hippocampal nerve cells in each dose group decreased, the arrangement was disordered, and the Nissellite bodies decreased. Western blotting results showed that compared with the control group, the expression level of RIP1 protein in the hippocampus of mice in high-dose group was higher, and the difference was statistically significant ( P <0.05). The expression levels of RIP3, MLKL and HSP90 in hippocampal tissue of mice in medium and high dose groups were increased, and the differences were statistically significant ( P<0.05). After siRNA intervention decreased the expression of HSP90 protein, the expressions of HSP90, RIP1, RIP3 and MLKL in Al (mal) 3 groups were increased, and the differences were statistically significant ( P<0.05) . Conclusion:Through RIP1/RIP3/MLKL pathway, HSP90 is involved in neuronal programmed necrosis and spatial memory impairment induced by maltol aluminum in C57 mice.

Objective:To investigate whether heat shock protein 90 (HSP90) participates in the necroptosis of C57BL/6 mouse neurons and spatial memory impairment induced by Aluminum maltol [Al (mal) 3] through RIP1/RIP3/MLKL pathway. Methods:In March 2022, Thirty-two C57 mice were randomly divided into control group, Low dose group, a medium dose group, and a high-dose group, with 8 mice in each group, and injected intraperitoneally with physiological saline, 20, 40, and 80, respectivelyμmol/kgAl (mal) 3 was administered, it was injected 5 days a week and discontinued 2 days for 60 days. Morris water maze test was used to test the spatial learning and memory ability of mice. Nissl staining was used to observe the pathological changes of brain tissue. The protein expression levels of RIP1, RIP3, MLKL and HSP90 in hippocampus were determined by Western blotting. Results:In the water maze experiment, compared with the control group, the number of mice crossing the platform decreased in each dose group, the difference was statistically significant ( H=9.50, P=0.023), and the number of mice crossing the platform was statistically significant among each dose group ( P <0.05). Compared with the control group, the number of hippocampal nerve cells in each dose group decreased, the arrangement was disordered, and the Nissellite bodies decreased. Western blotting results showed that compared with the control group, the expression level of RIP1 protein in the hippocampus of mice in high-dose group was higher, and the difference was statistically significant ( P <0.05). The expression levels of RIP3, MLKL and HSP90 in hippocampal tissue of mice in medium and high dose groups were increased, and the differences were statistically significant ( P<0.05). After siRNA intervention decreased the expression of HSP90 protein, the expressions of HSP90, RIP1, RIP3 and MLKL in Al (mal) 3 groups were increased, and the differences were statistically significant ( P<0.05) . Conclusion:Through RIP1/RIP3/MLKL pathway, HSP90 is involved in neuronal programmed necrosis and spatial memory impairment induced by maltol aluminum in C57 mice.

Objective:This study aims to explore the feasibility of ethical review and mutual recognition, focusing on the operational efficiency and review processes of the Ethics Committees in Tianjin′s third-level hospitals.Methods:A thorough online survey was conducted across tertiary hospitals in Tianjin, utilizing a detailed questionnaire. The survey primarily examined the operations and reviews of Ethics Committees from 2019 to 2022, evaluating the efficiency of ethical reviews, the effectiveness of clinical research administration, and the hospitals′ perspectives on mutual recognition of ethical reviews. From 29 collected responses, 28 were deemed suitable for in-depth statistical analysis.Results:In Tianjin′s 28 surveyed tertiary hospitals, 16 routinely hold ethics review meetings monthly. Nine hospitals have established pre-ethics review processes, and three have achieved mutual recognition of their ethical review outcomes. Additionally, five hospitals have integrated electronic information systems. From 2019 to 2021, there has been an increase in clinical trials and Investigator-Initiated Trials (IITs) under initial review, with a significant presence of multi-center clinical trials (90%) and multi-center IIT studies (75%). The timeframe for clinical research review opinions ranged from 18.84 to 20.69 days between 2019 and September 2022, while the duration for clinical research review approvals varied from 22.03 to 23.68 days. During the same period, clinical trial management efficiency spanned from 48.42 to 62.65 days, and IIT study management efficiency was between 25.54 to 28.17 days. Participants identified the main factors influencing management efficiency as stemming from research institutions and sponsors.The majority of hospitals expressed support for the advancement of mutual recognition of ethical reviews and the implementation of a unified submission checklist and template.Conclusions:The Ethics Committees in Tianjin′s third-level hospitals have progressively evolved towards standardization. There is a marked improvement in the efficiency of ethical reviews and overall management of clinical research, indicating a positive development towards more streamlined and effective ethical governance in clinical studies.

Objective To investigate the value of HALP score in evaluating the prognosis of patients with hepatocellular carcinoma (HCC) after hepatectomy and whether the nomogram based on HALP score could effectively predict the postoperative survival of patients. Methods A retrospective study was performed for the clinical data of 253 HCC patients who underwent surgical treatment in Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, from July 2013 to March 2020. The receiver operating characteristic (ROC) curve was plotted to calculate the optimal cut-off values of HALP score and other related indicators; the chi-square test was used to investigate the association between HALP score and clinicopathological features; the Kaplan-Meier method was used to plot survival curves, and the Log-rank test method was used for comparison. The univariate and multivariate Cox regression analyses were used to investigate the association of HALP score and other clinical parameters with the prognosis of patients. R3.6 was used to establish a nomogram; C-index and calibration curve were used to evaluate the predictive ability of the nomogram, and net reclassification index (NRI) and integrated discrimination improvement (IDI) were used to compare predictive ability between the nomogram model and the conventional model. Results The Kaplan-Meier analysis showed that the high HALP group had significantly better overall survival (OS) and recurrence-free survival (RFS) than the low HALP group ( P < 0.001). The univariate Cox regression analysis showed that white blood cell count, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), alpha-fetoprotein (AFP), surgical approach, microvascular invasion, TNM stage, degree of tumor differentiation, HALP, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR) were significantly associated with OS (all P < 0.05). The variables with statistical significance in the univariate Cox regression analysis were included in the multivariate Cox regression analysis, and the results showed that ALP, AST/ALT ratio, ALP, AFP, degree of tumor differentiation, and TNM stage were independent influencing factors for OS after surgery in HCC patients (all P < 0.05). The univariate Cox regression analysis showed that GGT, ALP, AFP, microvascular invasion, TNM stage, degree of tumor differentiation, HALP, AST/ALT ratio, NLR, and MLR were significantly associated with RFS (all P < 0.05), and the multivariate Cox regression analysis showed that HALP, AST/ALT ratio, NLR, ALP, AFP, and TNM stage were independent influencing factors for RFS after surgery in HCC patients (all P < 0.05). The nomograms for OS and RFS of HCC patients were established based on the multivariate analysis. The nomogram for OS had a C-index of 0.732 (95% confidence interval [ CI ]: 0.691-0.774) and an area under the ROC curve of 0.795, 0.791, and 0.775, respectively, in predicting 1-, 3-, and 5-year survival rates, and the nomogram for RFS had a C-index of 0.677 (95% CI : 0.637-0.717) and an area under the ROC curve of 0.742, 0.733, and 0.716, respectively, in predicting 1-, 3-, and 5-year survival rates. The calibration curves of 1-, 3-, and 5-year OS were well fitted to those of 1-, 3-, and 5-year RFS. Conclusion A low level of HALP before surgery is a predictive factor for poor long-term prognosis in HCC patients undergoing surgical treatment, and the nomogram model based on HALP score is superior to the BCLC staging model and can better predict the prognosis of HCC.