Objective The pathogenesis of EAP in rats based on the TLR4/NF-κB-NLRP3 inflammasome signaling pathway was explored.Methods Randomly divide 12 male SD rats into 4 groups using the number table,namely normal group(N),model group(M),Caspase-1 inhibitor group(Caspase-1),and NLRP3 inhibitor MCC950 group(NLRP3),with 3 rats in each group.After drug intervention,relevant indicators were observed by using HE staining,ELISA,WB methods.Results Compared with the N group,the M group rats had showed significant damage in prostate gland structure and infiltration of inflammatory cells.Compared with group N,the expression of TLR4,P-NF-κB P65,NLRP3,ASC,Cleaced-Caspase-1,Cleaced-IL-1β,and IL-18 proteins in the prostate tissue of group M rats had increased(P<0.01).Compared with group M,the expression of TLR4,P-NF-κB P65,NLRP3,ASC,Cleaced-Caspase-1,Cleaced-IL-1β,and IL-18 proteins in the NLRP3 and Caspase-1 groups had significantly reduced(P<0.01).The serum levels of IL-1 β,IL-6,IL-8,IL-17A,IL-18,IFN-γ,and TNF-α in group M rats had been significantly higher than those in group N(P<0.01).But the serum levels of IL-10 had been slightly lower and no statistical significance.The serum levels of IL-1β,IL-6,IL-8,IL-17A,IL-18,IFN-γ,and TNF-α in group M rats had been lower than those in group N(P<0.01 or P<0.05),the serum IL-10 level had increased(P<0.01).Conclusion The activation of TLR4/NF-κB-NLRP3 inflammasome signaling path-way promotes the occurrence and development of prostatitis in EAP rats.

OBJECTIVE: To explore the effect and mechanism of DNA methyltransferase 1 (DNMT1) knockout on the inhibition of acute myeloid leukemia (AML) by natural killer (NK) cells. METHODS: The peripheral blood NK cells of AML patients and controls were collected, and the mRNA and protein level of DNMT1 were measured by PCR and Western blot, respectively. The DNMT1 knockout mice were constructed to obtain NK^DNMT1-/- cells. The NK cells were stimulated with interleukin (IL)-12, IL-15, and IL-18 to construct memory NK cells, and then the interferon-γ (IFN-γ) levels were measured by ELISA. After co-culturing with memory NK cells and HL60 cells, the killing effect of NK^DNMT1-/- cells on HL60 cells was detected by LDH assay. Then, the HL60 cell apoptosis and NK cell NKG2D level were measured by flow cytometry. The perforin and granzyme B protein levels of NK cells were measured by Western blot. The AML model mice were constructed by injecting HL60 cells into the tail vein, meanwhile, memory NK cells were also injected, and then the mouse weights, CD33 positive rates, and survival time were detected. RESULTS: The mRNA and protein levels of DNMT1 in NK cells of AML patients were significantly higher than those in the control group (both P < 0.01), while the IFN-γ level induced by interleukin was significantly lower than that in the control group (P < 0.05). Compared with NK^DNMT1+/+ cells, the ability of NK^DNMT1-/- cells to secrete IFN-γ after interleukin stimulation was significantly increased (P < 0.05). The killing and apoptosis-inducing effects of NK^DNMT1-/- cells on HL60 cells were significantly stronger than those of NK^DNMT1+/+ cells (both P < 0.05). The NKG2D level and expression of perforin and granzyme B of NK^DNMT1-/- cells were significantly increased compared with NK^DNMT1+/+ cells (all P < 0.05). Compared with AML mice injected with NK^DNMT1+/+ cells, AML mice injected with NK^DNMT1-/- cells showed significantly increased body weight, decreased CD33 positive rate, and prolonged survival time (all P < 0.05). CONCLUSION Knocking out DNMT1 can enhance the inhibitory effect of NK cells on AML, which may be related to enhancing NK cell memory function.
Killer Cells, Natural/metabolism* ; Animals ; Leukemia, Myeloid, Acute ; Humans ; DNA (Cytosine-5-)-Methyltransferase 1 ; Mice ; Mice, Knockout ; HL-60 Cells ; Apoptosis ; Interferon-gamma/metabolism* ; Granzymes/metabolism* ; Perforin/metabolism* ; NK Cell Lectin-Like Receptor Subfamily K/metabolism*

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Progressive pulmonary fibrosis (PPF) is a progressive and lethal condition with few effective treatment options. Improvements in quality of life for patients with PPF remain limited even while receiving treatment with approved antifibrotic drugs. Traditional Chinese medicine (TCM) has the potential to improve cough, dyspnea and fatigue symptoms of patients with PPF. TCM treatments are typically diverse and individualized, requiring urgent development of efficient and precise design strategies to identify effective treatment options. We designed an innovative Bayesian adaptive two-stage trial, hoping to provide new ideas for the rapid evaluation of the effectiveness of TCM in PPF. An open-label, two-stage, adaptive Bayesian randomized controlled trial will be conducted in China. Based on Bayesian methods, the trial will employ response-adaptive randomization to allocate patients to study groups based on data collected over the course of the trial. The adaptive Bayesian trial design will employ a Bayesian hierarchical model with "stopping" and "continuation" criteria once a predetermined posterior probability of superiority or futility and a decision threshold are reached. The trial can be implemented more efficiently by sharing the master protocol and organizational management mechanisms of the sub-trial we have implemented. The primary patient-reported outcome is a change in the Leicester Cough Questionnaire score, reflecting an improvement in cough-specific quality of life. The adaptive Bayesian trial design may be a promising method to facilitate the rapid clinical evaluation of TCM effectiveness for PPF, and will provide an example for how to evaluate TCM effectiveness in rare and refractory diseases. However, due to the complexity of the trial implementation, sufficient simulation analysis by professional statistical analysts is required to construct a Bayesian response-adaptive randomization procedure for timely response. Moreover, detailed standard operating procedures need to be developed to ensure the feasibility of the trial implementation. Please cite this article as: Zhang C, Nie YS, Zhang CT, Yang HJ, Zhang HR, Xiao W, Cui GF, Li J, Li SJ, Huang QS, Yan SY. An adaptive Bayesian randomized controlled trial of traditional Chinese medicine in progressive pulmonary fibrosis: Rationale and study design. J Integr Med. 2025; 23(2): 138-145.
Female ; Humans ; Male ; Bayes Theorem ; Disease Progression ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Pulmonary Fibrosis/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Research Design ; Adaptive Clinical Trials as Topic

OBJECTIVE: Cancer remains a significant global health challenge, necessitating the development of effective treatment approaches. Developing synergistic therapy can provide a highly promising strategy for anti-cancer treatment through combining the benefits of various mechanisms. METHODS: In this study, we developed a synergistic strategy for chemo-photothermal therapy by constructing nanocomposites using gold nanorods (GNRs) and tetrahedral framework nucleic acids (tFNA) loaded with the anti-tumor drug doxorubicin (DOX). RESULTS: Our in vitro studies have systematically clarified the anti-cancer behaviors of tFNA-DOX@GNR nanocomposites, characterized by their enhanced cellular uptake and proficient lysosomal escape capabilities. It was found that the key role of tFNA-DOX@GNR nanocomposites in tumor ablation is primarily due to their capacity to induce cytotoxicity in tumor cells via a photothermal effect, which generates instantaneous high temperatures. This mechanism introduces various responses in tumor cells, facilitated by the thermal effect and the integrated chemotherapeutic action of DOX. These reactions include the induction of endoplasmic reticulum stress, characterized by elevated reactive oxygen species levels, the promotion of apoptotic cell death, and the suppression of tumor cell proliferation. CONCLUSION This work exhibits the potential of synergistic therapy utilizing nanocomposites for cancer treatment and offers a promising avenue for future therapeutic strategies.
Doxorubicin/chemistry* ; Gold/chemistry* ; Nanotubes/chemistry* ; Humans ; Nanocomposites/chemistry* ; Cell Line, Tumor ; Nucleic Acids/chemistry* ; Antibiotics, Antineoplastic/pharmacology* ; Antineoplastic Agents/administration & dosage*

Objective:To evaluate the effectiveness of a workshop-driven interactive teaching model in clinical alarm training for undergraduate nursing interns in the intensive care unit (ICU).Methods:A total of 120 undergraduate nursing students who interned in the ICU from November 2023 to April 2024 were enrolled and randomly assigned using a random number table into a control group ( n=60, traditional teaching) and an intervention group ( n=60, workshop-driven interactive teaching). Clinical alarm knowledge, attitudes, and practices (KAP); perception of patient safety culture; and training satisfaction were assessed before and after the training using validated questionnaires. Differences between groups were analyzed using independent sample t-test, paired sample t-test, chi-square test, and the Mann-Whitney U test with SPSS 22.0. Results:There were no significant differences between the two groups in clinical alarm KAP scores or patient safety culture perception scores before the training ( P>0.05). After the training, the intervention group showed significantly higher scores in clinical alarm KAP [(127.58±6.45) vs. (123.48±7.61), t=3.17, P=0.002] and patient safety culture perception [(99.44±9.17) vs. (95.45±12.03), t=-2.04, P=0.044] compared with the control group. Satisfaction with training content, teaching quality, and overall instructional design was significantly higher in the intervention group than in the control group ( P<0.05). Within-group comparisons showed that the intervention group had significant improvements in clinical alarm KAP [(127.58±6.45) vs. (120.10±10.25), t=-5.10, P<0.001] and patient safety culture perception [(99.44±9.17) vs. (94.46±12.12), t=-2.65, P=0.010] after training. No significant changes were observed in the control group after training ( P>0.05). Conclusions:The workshop-driven interactive teaching model can effectively enhance the clinical alarm KAP levels and patient safety culture perception among undergraduate nursing interns in the ICU. This teaching approach provides a scientific basis for optimizing clinical alarm education and cultivating high-quality nursing professionals.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.

Objective To explore the clinical characteristics,antimicrobial resistance,virulence and molecular epi-demiology characteristics of carbapenem-resistant hypervirulent Klebsiella pneumoniae(CR-hvKP).Methods Car-bapenem-resistant Klebsiella pneumoniae(CRKP)strains isolated from clinical specimens in a tertiary first-class teaching hospital from 2018 to 2021 were collected.ST1 1 CR-hvKP strains were screened through the detection of antimicrobial resistance genes and virulence genes as well as multilocus sequence typing(MLST).Basic clinical in-formation,antimicrobial resistance genes and virulence genes were analyzed.Twenty-three strains of ST1 1 CR-hvKP were randomly selected for virulence phenotype analysis;45 strains of CR-hvKP were randomly selected for homology analysis by pulsed-field gel electrophoresis(PFGE).Results There were a total of 124 clinically isolated strains of ST11 CR-hvKP from 2018 to 2021,mainly from the department of neurosurgery(33.87％).The major specimen source was sputum(56.45％),the average age of infected patients were(55.2±16.4)years old,and the majority were male patients(77.42％).Antimicrobial susceptibility testing results showed these strains were resis-tant to most clinically commonly used antimicrobial agents.Virulence detection showed that virulence varied among these strains,but most of them were hypervirulence strains.PFGE analysis results showed that the strains were mainly subtype A1(63.4％).Conclusion ST1 1 CR-hvKP presents multidrug resistance and hypervirulence.Clonal transmission of some strains exists in this hospital,which poses great challenges for clinical anti-infection treatment as well as prevention and control.It is necessary to strengthen the prevention and control of healthcare-associated infection.

Objective:To investigate the differences in clinical characteristics and prognosis between early- and late-onset rectal cancer (EORC and LORC, respectively), and to analyze the adverse factors affecting outcomes in EORC patients.Methods:This retrospective cohort and propensity score matching (PSM) study examined 904 rectal cancer patients who underwent radical resection at Peking University Shougang Hospital between 2017 and 2022. Prior to comparison, patients in the EORC group (<50 years old) and LORC group (≥50 years old) were matched at a 1:2 ratio to control for the following confounders: sex; neoadjuvant therapy; T, N, and M stage; and adjuvant treatment. Cox regression was used to identify independent risk factors for poor overall and progression-free survival (OS and PFS, respectively). Restricted cubic splines were used to analyze the association between age and clinical outcome.Results:A total of 199 EORC and 705 LORC patients were included for analysis. Prior to PSM, the proportions of patients with stage T4 [27.6%(55/199) vs.12.9%(91/705),χ 2=30.12, P<0.001] and M1 disease [24.6%(49/199) vs. 15.7% (111/705),χ 2=8.40, P=0.004], and the proportions of patients who received neoadjuvant [79.9% (159/199) vs. 62.3%(439/705), χ 2=21.54, P<0.001] and adjuvant therapy [62.8%(125/199) vs. 50.8% (358/705), χ 2=9.03, P=0.003] were significantly higher in the EORC group. Mean OS (57.8 vs. 51.9 months; P=0.011) and PFS (53.6 vs. 44.5 months; P=0.001) were also significantly longer in the LORC group. However, after PSM, the intergroup differences in OS and PFS were not significant ( P=0.450 and 0.180, respectively). Multivariate Cox regression in the EORC cohort identified carcinoembryonic antigen concentration ≥5 μg/L [hazard ratio (HR), 3.79; 95% confidence interval (CI), 1.34-10.69; P=0.012] and presence of perineural invasion (HR, 7.27; 95%CI, 1.77-29.88; P=0.006) as independent risk factors for overall mortality; the only independent risk factor for cancer progression was carcinoembryonic antigen concentration ≥5 μg/L (HR, 2.56; 95%CI, 1.06-6.17; P=0.037). Restricted cubic spline analysis showed a U-shaped relationship between age and clinical outcome. After PSM, OS and PFS did not show a significant association with age in the < 60 years old group. Conclusion:Compared with LORC, EORC is more likely to be diagnosed at a later stage and has a worse outcome. Early diagnosis and timely treatment improve outcome in EORC patients.