Enhancer-promoter communication is fundamental to the spatial and temporal control of gene expression. Cohesin-mediated loop extrusion has long been considered a major structural mechanism that brings distal regulatory elements into proximity with their target promoters. Recent findings from Aboreden et al. refine this view by showing that depletion of Nipped-B-like protein (NIPBL), a key regulator of cohesin loading and loop extrusion, markedly disrupts architectural chromatin loops, whereas many cis-regulatory contacts and broad post-mitotic transcriptional reactivation are only modestly affected. These observations suggest that loop extrusion is important, but not sufficient, for explaining productive regulatory communication. In this Comment, we discuss how transcriptional condensate-like assemblies may provide an additional biochemical and kinetic layer that helps convert regulatory proximity into transcriptional output. By locally enriching transcription factors, coactivators, mediator and RNA polymerase II(Pol II) around active loci, such regulatory hubs may stabilize productive enhancer-promoter encounters and modulate transcriptional activity. We further propose that transcriptional bursting provides a useful framework for understanding this conversion, because gene expression can be decomposed into burst frequency, burst duration and burst size. Integrating chromatin architecture, condensate organization and bursting dynamics may therefore provide a more complete view of how enhancer-promoter communication is re-established after mitosis and how regulatory proximity is converted into transcriptional output through mechanisms beyond loop extrusion.

Objective To investigate the critical role of macrophage M1 polarization in mediating the effect of periodontitis on the progression of chronic obstructive pulmonary disease(COPD).Methods Alveolar lavage fluid samples were collected from COPD patients with comorbid periodontitis,and gene expression analysis was performed to validate the changes in the expression of M1 polarization-related genes.A mouse model of COPD,with experimentally induced periodontitis,were established.Hematoxylin and eosin(HE)staining of pathological sections was performed to observe the effect of periodontitis on COPD progression.Flow cytometry,immunofluorescence staining,and reverse transcription quantitative polymerase chain reaction(RT-qPCR)were performed to analyze the effect of periodontitis on macrophage M1 polarization and the expression of relevant genes in the alveolar lavage fluid and lung tissues.Results In clinical samples of alveolar lavage fluid from COPD patients with periodontitis,the expression of macrophage M1 polarization-related genes,including CD86,inducible nitric oxide synthase(iNOS),interleukin(IL)-1β,tumor necrosis factor(TNF)-α,IL-23,and IL-6,was upregulated compared with that of COPD patients without periodontitis.Analysis of a mouse disease model revealed that periodontitis affected the growth of COPD mice,with the final body mass of mice in the periodontitis and COPD comorbid group([21.3±0.52]g,day 34)lower than that of the COPD group([23.93±0.45]g,day 34).Pathological sections of the lung tissue showed that periodontitis exacerbated COPD progression,with more pronounced alveolar expansion and alveolar wall destruction observed in the periodontitis and COPD comorbid group.Flow cytometry revealed a higher proportion of M1-polarized macrophages in alveolar lavage fluid from COPD and periodontitis comorbid mice([31.36±2.51]%)compared with the COPD mice([23.19±1.07]%).Immunofluorescence assays indicated that periodontitis also promoted macrophage M1 polarization in the lung tissue of COPD mice.Gene expression analysis demonstrated that M1 polarization-related gene expression was significantly upregulated in both the alveolar lavage fluid and lung tissue of mice in the COPD and periodontitis co-morbid group compared to the COPD group.Conclusion Periodontitis exacerbates COPD progression by promoting macrophage M1 polarization in the lungs.Enhancing oral hygiene management and targeting the inhibition of macrophage M1 polarization may represent new therapeutic strategies for the clinical prevention and control of COPD.

ObjectiveTo identify key factors influencing cognitive function in the elderly, including traditional Chinese medicine (TCM) constitutional classification, and to rank their relative importance.MethodsWe used cross-sectional data from seven geographical regions across mainland China. The Changsha version of the Montreal Cognitive Assessment was used to assess cognitive function. A “least absolute shrinkage and selection operator” (LASSO) model, multivariate linear regression analysis, and random forest (RF) model were used. Subgroup analyses were performed to examine the correlation between key TCM constitution types and cognitive function in different population subgroups.ResultsA total of 24 803 individuals aged 60 and above were included in the study. We selected 18 influential factors using the LASSO model. Higher education, being married, and having insurance were positively correlated with cognitive function in the elderly (all P .05). In contrast, poor sleep, vision impairment, hearing impairment, basic activities of daily living disability, instrumental activities of daily living disability, depression, hypertension, coronary heart disease, diabetes, stroke, yang-deficiency constitution (YADC), yin-deficiency constitution (YIDC), qi deficiency constitution (QDC), and blood stasis constitution (BSC) were negatively correlated with cognitive function (all P .05). YIDC and BSC affected all dimensions of cognitive function (all P .05). YADC mainly affected attention, language, abstraction (verbal analogies), memory, and orientation to time and place dimensions (P .001). QDC mainly affected language and abstraction (verbal analogies) dimensions (P .05). The negative correlations between BSC, YADC, YIDC, and QDC scores and cognitive function revealed statistically significant differences across most subgroups. The RF model identified education, BSC, and poor sleep quality as the three most influential factors in our study.ConclusionBSC, YADC, YIDC, and QDC were associated with cognitive decline in the elderly. Our findings provide new perspectives and significant references for interventions for early-stage cognitive disorders.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

OBJECTIVE To investigate the current status of monitoring indicators related to the"Perioperative In-fection Control"in medical institutions above the secondary level in Guizhou Province,and to delve into the imple-mentation of key measures for infection prevention and control during the perioperative period for patients under-going surgical operations.METHODS Based on the"Implementation Plan for the'Perioperative Infection Control'Initiative in Guizhou Province",a"Case Investigation Form on Key Measures for Infection Prevention and Control During the Perioperative Period for Patients Undergoing Surgical Operation"was developed.A total of 138 medi-cal institutions participated in the case investigation,and a total of 2 128 cases were investigated.RESULTS The overall monitoring indicators for the"Perioperative Infection Control"initiative in the 138 medical institutions a-bove the secondary level in Guizhou Province were at a relatively low level.The skin cleansing compliance rate was 80.32％,the hair removal compliance rate was 16.43％,the prophylactic antibacterial drug administration rate within 0.5-1 hour before surgery was 55.94％and the antibacterial drug discontinuation rate within 24 hours after prophylactic medication for type Ⅰ incision surgeries was 56.48％.The hair removal compliance rate was higher in tertiary medical institutions(19.21％)than in secondary medical institutions(14.34％)(P=0.039).The distri-bution of the four monitoring indicators varied in clinical departments and surgery types,with statistically signifi-cant differences(P＜0.05).The preferred method for surgical site skin cleansing in medical institutions across the province was local wiping,primarily with clean water(57.21％).The primary method for hair removal was razors(68.82％),and hair removal on the day of surgery was most common(61.75％).CONCLUSIONS Conduc-ting a survey on the current status of"Perioperative Infection Control"initiative monitoring indicators in medi-cal institutions in Guizhou Province helps to understand the implementation of key measures for perioperative in-fection prevention and control and set intervention targets,thus providing references for establishing a dynam-ic monitoring indicator change mechanism.

Objective:To clarify the prognostic significance of 1q21 amplification in multiple myeloma(MM),and explore the efficacy and prognosis of ixazomib in the treatment of MM patients with 1q21 amplification.Methods:A retrospective analysis of clinical data was conducted on 77 patients with newly diagnosed MM who were hospitalized in Zhongshan Hospital,Xiamen University from January 2010 to December 2022.To analyze the clinical features of MM patients with 1q21 amplification,evaluate the mitigation rate and survival treated with ixazomib-based regimens.Results:Among the 77 newly diagnosed MM patients,40 patients had 1q21 amplification,while 37 didn't.Multivariate Cox regression analysis revealed that 1q21 amplification was an independent risk factor affecting the prognosis of MM patients(P＜0.05).Compared to patients without 1q21 amplification,those with 1q21 amplification had poorer progression-free survival(PFS)and overall survival(OS)(both P＜0.05).When the 1q21 amplification ratio exceeded 66.7％,both PFS and OS were worse(P＜0.05).There were no statistical differences in the deep remission rate(≥VGPR),overall response rate and PFS between the 1 q21 amplification positive and negative groups treated with ixazomib-based regimens(P＞0.05),but OS showed a significant difference(P＜0.05).Among the patients who switched to ixazomib treatment from bortezomib,there was a statistically significant difference in the complete response rate(P＜0.05).Compared to other treatment regimens,ixazomib-based regimens resulted in a significant reduction in adverse reactions such as peripheral neuropathy(P＜0.05).Conclusion:Ixazomib-based chemotherapy regimens can overcome the poor prognosis associated with 1q21 amplification and improve mitigation rates and PFS in patients.Ixazomib has low incidence of adverse reactions,good safety profile and prolonged duration of therapy.

Thoracic anesthesia with spontaneous respiration represents a form of precision anesthesia meticulously customized to individual patients.Considering the more stringent requirements this anesthesia approach imposes on the regulation of respiratory function,the writing group of the"Consensus of Experts on the Management of Thoracic Anesthesia with Spontaneous Respiration"has formulated elaborate guidelines regarding indications and contraindications,preoperative evaluation,anesthesia implementation,common complications,and treatment strategies.This was accomplished by referencing relevant domestic and international literature and integrating it with actual clinical requirements.The objective is to standardize the rational application of this anesthesia method.

The Guidelines for Occupational Hazard Assessment and Control of Active Pharmaceutical Ingredient in the Pharmaceutical Industry (T/WSJD 60—2024) is the first guiding standard in the field of health in China that focuses on occupational health protection for active pharmaceutical ingredient (API). It covers the general principles, work procedures, assessment methods, and control strategies for API occupational hazard assessment, providing practical guidance and recommendations for pharmaceutical enterprises to eliminate or reduce occupational health risks associated with API, improve working environment, and enhance refined management practices. This article interpreted and analyzed the background of standard establishment, formulation process, fundamental basis, and main content, to provide scientific and comprehensive technical support for occupational health managers in the pharmaceutical industry to better apply this standard.