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 explore the effect of preoperative intensive functional training on the balance and functional recovery of patients with knee osteoarthritis (KOA) receiving total knee arthroplasty (TKA).Methods:Sixty KOA patients were randomly divided into an outpatient group, a home-based group and a control group, each of 20. Before their TKAs, both the outpatient and home-based groups underwent intensive functional training for 4 weeks, while the control group did nothing special. After the TKA, all received 4 weeks of standardized postoperative rehabilitation training. Before any training, after the 4 weeks of preoperative training and 4 weeks after the TKAs, all of the subjects performed the timed up and go test (TUGT), and their joint range of motion (ROM) was recorded. They also completed the 30-second chair stand strength test (30sCST), and the 6-minute walk exercise endurance test (6MWT). KOA osteoarthritis indices (WOMACs) were also recorded.Results:After the 4 weeks of preoperative training, significant differences were observed in the trajectory length, elliptical area and TUGT times of both the outpatient and home-based groups. Four weeks after the TKAs, significant differences were observed in all of the measurements in all three groups, but the results of the outpatient and home-based groups were significantly better than those of the control group, on average. After the 4 weeks of postoperative training, there were significant differences between the outpatient and home-based groups in terms of the average knee flexion angle, knee extension angle, 30sCST and 6MWT results. There were significant differences among the 3 groups in all of the measurements 4 weeks after the TKAs, with those of the two training groups showing significantly better results than the control group. The pain scores, stiffness scores, function scores and total WOMAC scores had improved significantly compared with the control group, but the average function and total WOMAC scores of the outpatient group (24.25±2.38) and (35.41±3.02) were then significantly superior to the home-based group′s averages.Conclusions:Intensive preoperative functional training conducted in an outpatient clinic or at home can significantly improve the balance, lower limb strength, exercise endurance and symptoms of KOA patients after TKA.

Objective:To investigate the effect of progressive resistance training on inflammatory markers, motor function and quality of life in the elderly after total knee arthroplasty (TKA).Methods:This study was a randomized controlled trial. A total of 46 elderly patients aged≥60 years who underwent total knee arthroplasty in the Affiliated Hospital 6 of Nantong University from January 2023 to June 2024 were selected and divided into experimental group and control group by computer random number method (23 cases in each group). The control group received routine rehabilitation management intervention, progressive resistance training was added to the experimental group on the basis of the control group, and all patients were intervened for 4 weeks. Interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), 30-Second Chair Stand Test (30sCST), Knee Society Score (KSS), and World Health Organization Quality of Life Scale-Brief Form Questionnaire (WHOQOL-BREF) scores were measured at 1 day before operation, 2 weeks and 4 weeks after operation, and were compared respectively.Results:At 2 and 4 weeks after operation, the levels of IL-6 [(22.44±2.17) and (9.91±1.41) pg/ml], CRP[(19.61±2.20) and (3.17±0.40) mg/L] and ESR[(44.85±3.78) and (28.28±3.31) mm/1 h] in the experimental group were significantly lower than those in control group [IL-6: (24.65±1.77) and (11.35±1.67) pg/ml, CRP: (23.24±2.69) and (4.15±0.45) mg/L and ESR: (48.54±3.66) and (34.60±2.98) mm/1 h](all P<0.05). At 2 and 4 weeks after operation, the 30sCST[(9.87±0.92) and (11.83±1.03) times], clinical scores of KSS[(48.44±3.13) and (71.09±3.30) points], functional scores of KSS[(40.44±3.96) and (69.35±4.07) points] in the experimental group were significantly higher than those in control group [30sCST: (9.30±0.70) and (10.52±0.79) times, clinical scores of KSS: (46.17±2.86) and (67.00±2.89) points, functional scores of KSS: (38.91±3.68) and (66.30±5.05) points](all P<0.05). At 2 weeks after operation, the scores of physical health, mental health and social relations in the WHOQOL-BREF of the experimental group [(16.96±1.02), (17.96±1.46) and (6.74±0.62) points], which were significantly higher than those in the control group [(16.09±1.08), (17.14±1.12), (6.44±0.51) points](all P<0.05). There was no significant difference in the environmental condition score between the two groups. At 4 weeks after operation, the scores of physical health, mental health, social relations and environmental conditions in WHOQOL-BREF of the experimental group [(22.09±1.81), (22.17±2.19), (12.09±1.28) and (33.91±2.26) points] were significantly higher than those in the control group [(19.65±1.80), (20.39±1.95), (10.17±1.30), (31.96±2.51) points] (all P<0.05). Conclusion:Progressive resistance training can effectively reduce the inflammatory response in the elderly after total knee arthroplasty, enhance lower limb muscle strength and knee joint function, and improve the quality of life.

Hand degloving injury represents one of the most severe forms of hand trauma, characterised by challenging treatment and a complex prognostic outcome. It is crucial to effectively utilise the degloved tissues in emergency or primary repair of a hand degloving injury. This consensus provides a comprehensive review of the existing literature on definition, classification, emergency assessment, debridement, judgment of skin viability, in situ repair of the degloved skin, and adjunctive treatment for degloving injury of hand. Based on conclusion of both domestic and international experiences, this expert consensus on the classification of hand degloving injury and the emergency repair with the avulsed skin is established, aiming to provide a guidance to surgeons on standardised treatment strategy and improve the management of hand degloving injury.

Objective To develop and translate the Chinese listening self-efficacy questionnaire(C-LSEQ)and to test its reliability and validity.Methods A total of 172 subjects aged≥60 years with age-related hearing loss completed the C-LSEQ questionnaire via direct interviews.Pure tone hearing threshold test,Mandarin hearing in noise test,and the hearing handicap inventory for elderly-screening(HHIE-S)were evaluated.Twenty subjects were randomly selected from the original group to complete the C-LSEQ questionnaire in 2 weeks after the initial evaluation.Results ① Reliability:The Cronbach's a coefficients of the three sub-dimensions and the overall ques-tionnaire were all＞0.8,and the test-retest reliability coefficients of the three sub-dimensions and the overall ques-tionnaire were all＞0.9(P＜0.001).② Validity:The experts collectively evaluated the representativeness of the statements with good content validity.The convergent validity test showed that the composite reliability(CR)of the 2 sub-dimensions and the overall questionnaire were all＞0.7,and the average variance extracted(AVE)were all＞0.5.The CR value of the complex listening dimension was 0.655,and the AVE value was 0.937.The criterion validity test showed that the overall questionnaire and the three sub-dimensions of the C-LSEQ were significantly correlated with the pure-tone average,speech recognition thresholds in noise,and HHIE-S(P＜0.001).Conclusion The C-LSEQ exhibits stable structure,with good reliability and validity.It can be used to assess listen-ing self-efficacy in adults with hearing loss,especially in the elderly with age-related hearing loss.

OBJECTIVE:The quality of systematic reviews/meta-analyses directly affects the reliability of clinical decision-making basis.Currently,there is no literature quality research on the systematic reviews/meta-analyses of platelet rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis both domestically and internationally.This article will comprehensively evaluate the methodological quality,reporting quality,and evidence quality of the systematic reviews/meta-analyses of platelet rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis.METHODS:Computer searches were conducted on CNKI,WanFang Data,VIP,CBM,PubMed,Embase,and The Cochrane Library.From the establishment of the database until January 24,2024,all systematic reviews/meta-analyses treated with platelet rich plasma versus hyaluronic acid for knee osteoarthritis were collected.Two evaluators independently conducted literature screening and data extraction,and used the AMSTAR 2,PRISMA 2020,and GRADE systems to evaluate and summarize the methodological,reporting,and evidence quality of the included systematic reviews/meta-analyses.RESULTS:A total of 18 qualified systematic reviews/meta-analyses were included,and the results showed that the efficacy and safety of platelet rich plasma might be better than that of hyaluronic acid.The methodological quality of all 18 studies was extremely low;4 reports had poor quality and relatively serious information defects,while 14 reports had moderate quality and some information defects.Among the 275 outcome measures of 16 systematic reviews/meta-analyses,there were 9 medium quality evidence,90 low-quality evidence,and 176 extremely low-quality evidence,with no high-quality evidence.CONCLUSION:At present,the quality of systematic reviews/meta-analyses literature on the treatment of knee osteoarthritis with platelet rich plasma versus hyaluronic acid is relatively low.In the future,the authors of the systematic reviews need to strictly follow the entries of quality evaluation tools such as AMSTAR 2 and PRISMA 2020 in terms of plan registration,research type explanation,retrieval strategy,exclusion list,research site and funding source,bias risk analysis,publication bias evaluation,and public information acquisition,and conduct evidence quality evaluation on the combined results of the systematic reviews/meta-analyses to provide more reliable and rigorous evidence-based basis for clinical practice.

Proteolysis-targeting chimeras (PROTACs) have shown considerable therapeutic potential across diverse fields such as cancer, inflammation, and neurodegenerative diseases, with numerous candidates already progressing into clinical trials. More recently, their application in antiviral therapy has been rapidly gaining momentum. This review systematically outlines the mechanistic foundations and design principles of PROTACs, highlights recent advances targeting coronaviruses (including SARS-CoV-2), hepatitis C virus, human immunodeficiency virus, and influenza viruses, and critically assesses key challenges—particularly the limited diversity of E3 ligase ligands, suboptimal oral bioavailability, and the lack of integrated platforms for druggability evaluation. Looking ahead, innovations in ligand discovery, pathway modulation, delivery technologies, and conditionally activated PROTAC designs are anticipated to overcome these barriers, ushering in a new era of precise and effective antiviral therapeutics.

Objective:To summarize and analyze the clinical characteristics, drug resistance and treatment of 36 neonates with Enterobacter sepsis in the Children′s Hospital of Soochow University in the past 3 years, so as to provide reference for clinical treatment.Methods:A retrospective analysis was conducted on neonates hospitalized in the Department of Neonatology of the Children′s Hospital of Soochow University from January 2021 to March 2024 who were diagnosed with Enterobacter sepsis. The birth status, clinical manifestations, blood culture drug sensitivity, treatment status and disease outcome of the neonates were analyzed.Results:A total of 36 neonates with Enterobacter sepsis were collected. Premature infants accounted for 38.9%(14/36), and late-onset cases accounted for 66.7%(24/36). The incidence of complications was high. The main complications were central nervous system infection (15/36, 41.7%), urinary system infection (13/36, 36.1%) and neonatal necrotizing enterocolitis (7/36, 19.4%). The main pathogenic bacteria were Escherichia coli (19 cases) and Klebsiella (11 cases). Among the 19 escherichia coli strains, 7 were extended-spectrum β-lactamase (ESBL)-producing strains and 1 was carbapenem-resistant enterobacteriaceae (CRE) strain. Among the 11 Klebsiella strains, 9 were ESBL-producing strains and 6 were CRE strains. The 6 neonates with CRE sepsis were treated with sensitive antibiotics such as meropenem, amikacin and ceftazidime-avibactam, and achieved good therapeutic effects.Conclusions:Escherichia coli and Klebsiella are the main pathogens of Enterobacter sepsis in neonates, especially premature infants, with high incidence of complications and high drug resistance rate.

Objective:To identify the risk factors and their predictive value for complications in neonates with early-onset group B streptococcus (GBS) sepsis. Methods:This case-control study retrospectively analyzed 96 neonates with early-onset GBS sepsis (age of onset<7 days) admitted to Children's Hospital of Soochow University between January 1, 2007, and December 31, 2022. Patients were categorized into complication ( n=36) and non-complication ( n=60) groups. Receiver operating characteristic (ROC) curves determined optimal cutoff values of Pediatric Sequential Organ Failure Assessment (pSOFA) and Pediatric Logistic Organ Dysfunction Score 2 (PELOD-2) for predicting complications in the neonates with early-onset GBS sepsis. Independent t-tests, Mann-Whitney U tests, Chi-square tests and Fishe exact tests were used for group comparison of general information, clinical manifestations, auxiliary examinations, and treatment during hospitalization. Multivariate logistic regression identified independent risk factors, and ROC curves evaluated their predictive performance for complications in the neonates with early-onset GBS sepsis. Results:ROC analysis identified pSOFA>4.5 scores and PELOD-2>5.5 scores as optimal thresholds for complication prediction in neonates with early-onset GBS sepsis. (1) The complication group exhibited higher rates of preterm birth [30.6% (11/36) vs. 5.0% (3/60), χ2=11.80], maternal clinical chorioamnionitis [25.0% (9/36) vs. 5.0% (3/60), χ2=6.50], prolonged rupture of membranes≥18 h [22.2% (8/36) vs. 5.0% (3/60), χ2=4.99], invasive mechanical ventilation [36.1% (13/36) vs. 13.3% (8/60), χ2=6.83], fever [22.2% (8/36) vs. 3.3% (2/60), χ2=6.70], lethargy [77.8% (28/36) vs. 51.7% (31/60), χ2=6.48], mottled skin as the initial clinical manifestation [38.9% (14/36) vs. 20.0% (12/60), χ2=4.07], leukopenia [44.4% (16/36) vs. 18.3% (11/60), χ2=7.59], hypoalbuminemia [27.8% (10/36) vs. 3.3% (2/60), χ2=10.16], pSOFA>4.5 [83.3% (30/36) vs. 35.0% (21/60), χ2=21.11], PELOD-2>5.5 [50.0% (18/36) vs. 5.0% (3/60), χ2=26.66], and dual-positive blood and cerebrospinal fluid cultures [25.0% (9/36) vs. 0.0% (0/60), Fisher exact test] compared to the non-complication group (all P<0.05). Serum creatinine [(88.4±17.7) vs. (61.9±17.7) μmol/L, t=－6.02], urea nitrogen [(3.7±0.4) vs. (3.4±0.6) mmol/L, t=－3.18], and lactate [(7.5±3.4) vs. (5.8±2.2) mmol/L, t=－2.80] were elevated, while fibrinogen [(2.2±1.1) vs. (2.7±1.0) g/L, t=2.03], pH (7.3±0.2 vs. 7.4±0.1, t=2.04), and albumin [(28.2±3.9) vs. (31.9±4.2) g/L, t=4.32] were reduced in the complication group (all P<0.05). (2) Multivariate analysis identified preterm birth ( OR=6.642, 95% CI: 1.210-36.473), along with hypoalbuminemia ( OR=8.202, 95% CI: 1.184-56.811), pSOFA>4.5 scores ( OR=5.284, 95% CI: 1.573-17.749), and PELOD-2>5.5 scores ( OR=8.464, 95% CI: 1.922-37.279) assessed on admission day 1 as independent risk factors (all P<0.05). The area under the curve for predicting complications in early-onset GBS sepsis neonates was 0.628 (95% CI: 0.523-0.724) for preterm birth, and 0.622 (95% CI: 0.517-0.719), 0.742 (95% CI: 0.642-0.826), and 0.725 (95% CI: 0.624-0.811) for hypoalbuminemia, pSOFA>4.5 scores, and PELOD-2>5.5 scores assessed on admission day 1, respectively. The combined predictive model integrating all four risk factors achieved the highest area under the curve of 0.868 (95% CI: 0.784-0.929). Conclusion:Preterm birth as well as hypoalbuminemia, pSOFA>4.5 scores, and PELOD-2>5.5 scores at admission are critical risk factors for complications in early-onset GBS sepsis, warranting heightened clinical vigilance.

AIM:This study aims to investigate of perodic expression,distribution and interaction between es-trogen receptor α(ERα)and ClC-3 chloride channel,and their relevance to the cell cycle specificity of tamoxifen(TAM)in anti-breast cancer treatment.METHODS:We utilized a web database to analyze the correlation between ERα and ClC-3 expression.Three-dimentional molecular simulation software and co-immunoprecipitation were employed to detect and analyze the interactions between these two proteins.To assess cell cycle dynamics,we performed thymidine(TdR)double-blocking release assay and used nocodazole to block the cell cycle,with subsequent analysis via flow cytometry.Cell viability was measured by MTT assay.Western blot was conducted to evaluate the protein expression levels of ERα and ClC-3,while immunofluorescence staining was utilized to assess their subcellular distribution.RESULTS:(1)Anal-ysis from the web database revealed a significant correlation between ERα and ClC-3 expression,and co-immunoprecipita-tion confirmed their interaction.(2)We successfully obtained human breast cancer T47D cells at different cycle stages us-ing the TdR double-blocking release method and nocodazole treatment.(3)Treatment with TAM primarily inhibited T47D cell viability during G2/M phase.(4)Both ERα and ClC-3 exhibited cyclic variations in protein expression,with their sub-cellular distributions showing periodicity and co-localization.(5)Protein interactions between ERα and ClC-3 were ob-served across all cell cycle phases;(6)After TAM treatment,ERα expression peaked in G2/M phase,while ClC-3 expres-sion remained unaffected.CONCLUSION:Our findings demonstrate cyclic differences in the expression and distribution of ERα and ClC-3 in human breast cancer T47D cells,along with confirmed interactions between these two proteins.The cyclic properties of ERα may play a role in mediating the cell cycle specificity of TAM's anti-breast cancer effect.