[摘 要] 树突状细胞（DC）是连接固有免疫与适应性免疫的核心枢纽，其功能稳态是介导肿瘤免疫监视的关键。然而，肿瘤微环境（TME）通过营养竞争及免疫抑制代谢产物的累积，驱动DC发生代谢重编程，进而诱导免疫应答功能缺陷。本文系统综述了TME中DC各亚型在三大代谢层面的重塑机制：糖代谢层面，高乳酸微环境通过GPR81信号抑制MHC-Ⅱ类分子表达，削弱传统树突状细胞（cDC）的抗原提呈能力；脂代谢层面，Wnt5a-β-catenin-PPARγ-CPT1A轴介导的脂肪酸氧化促进cDC向免疫抑制表型极化；氨基酸代谢层面，Arg1-IDO1通路的级联激活诱导DC获得耐受表型。针对上述代谢异常，当前干预策略已由单一靶点调控拓展至多模式联合，包括基于脂质纳米颗粒的原位疫苗与mRNA递送系统、代谢-免疫协同阻断，以及代谢状态优化的DC疫苗等。因此，深化对DC代谢检查点的认知，并靶向干预关键代谢检查点，不仅有望逆转免疫抑制微环境、克服治疗耐药，更为开发新一代代谢-免疫联合疗法提供了重要的科学依据与转化策略。

Effective symptom management can alleviate the physical and psychological distress experienced by patients with cancer, improve quality of life, and contribute to treatment adherence and improve clinical outcomes. However, most existing guidelines are developed for healthcare professionals, and patients and the public have limited access to standardized and comprehensible guidance on symptom management. To address this gap and to facilitate effective communication and shared decision-making, this study proposes the development of a patient version of the cancer symptom management guideline. The development process will adhere to the methodological framework recommended by the Guidelines International Network and the World Health Organization. The GRADE approach will be employed to assess the certainty of evidence and to formulate recommendations. In addition, the process will be informed by the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument and the Reporting Items for Practice Guidelines in Healthcare-Public or Patient Versions of Guidelines (RIGHT-PVG). This protocol outlines the establishment of the guideline working group, the identification and prioritization of key questions, evidence retrieval and appraisal, and the formulation of recommendations, with the aim of ensuring methodological rigor and transparency in the development of the patient guideline and providing methodological reference for similar guideline initiatives.

Objective To investigate the effects of early statin therapy on collateral circulation,responsible vessel improvement,and thromboxane B2(TXB2)/prostaglandin F1(PGF1α)in acute ischemic stroke with large vessel occlusion(AIS-LVO).Methods From May 2021 to May 2023,105 AIS-LVO patients treated with statins within 3 days of admission were selected as the statin group from the Neurology Department of Taiyuan Iron and Steel(Group)General Hospital.Concurrently,105 early AIS-LVO patients not treated with statins were selected as the non-statin group.The study compared symptom scores[National Institutes of Health Stroke Scale(NIHSS),modified Rankin Scale(mRS),Swallowing Standard Assessment(SSA),and Functional Oral Intake Scale(FOIS)scores],responsible vessel improvement,TXB2/PGF1α levels,and endothelial function indicators[basic fibroblast growth factor(bFGF)and circulating endothelial cells(CECs)].Results Af-ter 1 and 2 weeks,the statin group showed lower NIHSS,mRS,and SSA scores,and higher FOIS scores compared to the non-statin group(P<0.02).The statin group demonstrated higher rates of responsible vessel velocity increase,collateral circulation compensation,and superior CTA collateral circulation grading(P<0.05).At 1 and 2 weeks,the statin group had lower TXB2 and TXB2/PGF1α levels,and higher PGF1α levels compared to the non-statin group(P<0.02).The statin group showed lower bFGF levels and higher CECs levels(P<0.02).After 3 months,the statin group had a higher proportion of mRS scores of 0～2(P<0.05).Conclusion Early statin therapy in AIS-LVO patients can improve responsible vessel blood flow and endothelial function,regulate TXB2/PGF1α levels,promote collateral circulation compensation,and enhance swallowing and neurological function recovery.

Intestinal tuberculosis (ITB) is a specific infection caused by Mycobacterium tuberculosis invading the intestinal wall, encompassing two types: primary and secondary. In clinical practice, it is more commonly secondary to extrapulmonary tuberculosis, such as cavitary pulmonary tuberculosis. In recent years, the incidence of ITB has shown an increasing trend. Due to its insidious onset and the lack of obvious or specific early symptoms, early diagnosis is challenging, often leading to a prolonged disease course. Therefore, accurate early diagnosis is of great significance for the control and prevention of ITB. Currently, the primary diagnostic methods for tuberculosis include etiological examination, histopathological evaluation, molecular biological diagnosis, and imaging studies. This article summarizes recent advances in the application of these diagnostic techniques for ITB, aiming to provide valuable insights for healthcare professionals.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

(+)-Strebloside, a significant bioactive compound isolated from the roots of Streblus asper Lour., demonstrates inhibitory effects against multiple malignancies. However, its specific function and underlying mechanistic pathways in Non-Hodgkin lymphoma (NHL) remain unexplored. This investigation sought to elucidate the role and potential mechanisms of (+)-strebloside-induced NHL cell death. The results demonstrated that (+)-strebloside significantly induced apoptosis and ferroptosis in NHL cells, including those from Raji cell-derived xenograft models. Mechanistic analyses revealed that (+)-strebloside enhanced six-transmembrane epithelial antigen of prostate 3 (STEAP3)-induced ferroptosis in NHL, and STEAP3 inhibition reduced the proliferation-inhibitory effects of (+)-strebloside. Furthermore, (+)-strebloside suppressed NHL proliferation through the mitogen-activated protein kinase (MAPK) pathway, and extracellular signal-regulated kinase (ERK) inhibition diminished the proliferation-inhibitory activity induced by (+)-strebloside. These findings indicate that (+)-strebloside presents promising therapeutic potential for NHL treatment.
Humans ; Ferroptosis/drug effects* ; Lymphoma, Non-Hodgkin/physiopathology* ; Cell Line, Tumor ; MAP Kinase Signaling System/drug effects* ; Animals ; Cell Proliferation/drug effects* ; Mice ; Apoptosis/drug effects* ; Membrane Proteins/genetics* ; Xenograft Model Antitumor Assays ; Male ; Mice, Nude

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

At present,the laboratory medicine industry in China has developed rapidly,with various new technologies and methods emerge one after another. However,the current training process of laboratory medicine technology professionals still follows a training model that emphasizes theyory over practice,and the quality of training personnel is far from the requirments of the current development of the laboratory medicine industry in China. In order to effectively alleviate the current situation of the shortage of practical high-quality laboratory medicine talents,it is urgent to reform the teaching of laboratory medicine. The author of this paper puts forward the "Four-in-one" personnel training mode which is suitable for the development of laboratory medicine in China. It is proposed to explore a new teaching mode on the basis of the existing one,giving full play to the students' initiative and innovation,and providing new ideas for training high-quality laboratory medicine professionals.