[摘 要] 目的：探究着丝粒蛋白M（CENPM）在脑胶质瘤中的表达特征、临床预后价值及其对肿瘤恶性生物学行为的调控机制，为脑胶质瘤的精准治疗提供潜在靶点。方法：基于中国胶质瘤基因组图谱（CGGA）和癌症基因组图谱（TCGA）数据库分析CENPM在胶质瘤中的表达及其与患者临床病理特征和预后的相关性。通过基因本体论（GO）分析、京都基因与基因组百科全书（KEGG）富集分析和单细胞转录组分析探索CENPM的生物学功能和作用机制。WB法检测CENPM在胶质瘤细胞（LN-18、LN-229、U-138MG、U-251MG）和正常胶质细胞（HEB）中的表达；构建CENPM敲低细胞后，通过CCK-8、集落形成、Transwell和划痕实验评估恶性表型改变。结果：CENPM在WHO高级别胶质瘤中呈高表达（P < 0.05），与肿瘤恶性程度正相关。高表达组患者总体生存期显著短于低表达组（P < 0.01），Cox回归证实CENPM是影响胶质瘤患者预后的独立危险因素（P < 0.05）。功能富集分析结果显示CENPM相关基因主要富集于细胞周期调控、PI3K-Akt通路和免疫相关过程。单细胞分析结果显示CENPM主要在CD8⁺ T细胞高表达，并通过PTN-PTPRZ1/NCL配受体调控细胞通信。体外实验证实CENPM在胶质瘤细胞表达高于正常胶质细胞（LN-18：P < 0.01，LN-299：P < 0.05）；敲低CENPM显著抑制迁移（P < 0.05），但增强集落形成，提示其在肿瘤进展中的双重调控作用。结论：CENPM作为胶质瘤独立预后危险因子，通过调控细胞周期、PTN通路和免疫微环境驱动肿瘤进展，其差异化调控机制（抑制迁移、促进增殖）具有潜在的临床转化价值，可作为分子分型和靶向治疗候选标志物。

Lung cancer constitutes the most prevalent and lethal malignant tumor in China. Approximately 85% of lung cancer diagnoses correspond to the non-small cell histological subtype [non-small cell lung cancer (NSCLC)]. Despite surgery being the mainstay for early-stage disease, postoperative recurrence remains high and adjuvant chemotherapy offers limited benefit. In recent years, targeted therapy has demonstrated substantial advantages in driver mutation-positive NSCLC. To this end, the Lung Cancer Medical Education Committee of the Chinese Medical Education Association developed guidelines based on a systematic review of evidence through November 2025, using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach and a modified Delphi method. Focusing on epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and addressing ROS proto-oncogene 1 (ROS1), B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E mutation, and mesenchymal-epithelial transition factor (MET) exon 14 (METex14) skipping, the guideline covers molecular testing, neoadjuvant/adjuvant therapy, perioperative strategies, minimal residual disease monitoring, and postoperative surveillance. It defines testing requirements, specifies stage-directed and subtype-specific treatments, and standardizes minimal residual disease monitoring. These recommendations emphasize precision and feasibility to improve survival and quality of life.

Coronary heart disease （CHD） has a distinct circadian rhythmicity in its onset， which is closely related to the waxing and waning of qi and blood in the channel passages of the human body. Grounded in the circadian rhythm theory of "correspondence between heaven and humankind"， this paper explores the pathogenic evolution rules of qi-blood disharmony， channel obstruction， interacting as cause and effect with circadian rhythm disorders in CHD. Clinically， CHD can be observed to attack in the early morning， at night， in the afternoon， and at fixed or unfixed circadian intervals. The pathogenesis rhythms at different time nodes can correspondingly reflect the susceptibility tendencies and pathological stress responses of the human body to core pathogeneses such as yang deficiency with cold congelation， yin deficiency with yang floating， qi and yin deficiency， and liver constraint with qi stagnation under specific temporal states. Treatment should be adapted to the season and time， regulating yin and yang in accordance with biological rhythms. It is recommended to regulate qi during the daytime by promoting ascending and dispersing to unblock the channel passages， and select the appropriate timing for administration to harness natural timing. At the Mao （卯） hour， yang ascends while yin descends， and taking medication at this time conforms to the ascending of yang qi. At the Wu （午） hour， the heart meridian is active， and taking medication at this time warms the channel passages and assists heart yang， which can be treated with modified Buzhong Yiqi Decoction （补中益气汤） or Shengyang Yiwei Decoction （升阳益胃汤）. At night， blood should be harmonized， when the channel passages are unblocked through nourishing， restraining， and searching， with Lianmei Decoction （连梅汤） combined with Dahuang Zhechong Pill （大黄䗪虫丸）. Following the temporal rhythm， the focus is put on the transitional time of day and night and the four seasons to treat disease before it arises， resonating and corresponding with the natural rhythm.

OBJECTIVE To construct three-class （insufficient， normal， excessive） and two-class （insufficient， normal） models for predicting plasma concentration of valproic acid （VPA）， and compare the performance of these two models， with the aim of providing a reference for formulating clinical medication strategies. METHODS The clinical data of 480 patients who received VPA treatment and underwent blood concentration test at the Xi’an International Medical Center Hospital were collected from November 2022 to September 2024 （a total of 695 sets of data）. In this study， predictive models were constructed for target variables of three-class and two-class models. Feature ranking and selection were carried out using XGBoost scores. Twelve different machine learning algorithms were used for training and validation， and the performance of the models was evaluated using three indexes: accuracy， F1 score， and the area under the working characteristic curve of the subject （AUC）. RESULTS XGBoost feature importance scores revealed that in the three-class model， the importance ranking of kidney disease and electrolyte disorders was higher. However， in the two-class model， the importance ranking of these features significantly decreased， suggesting a close association with the excessive blood concentration of VPA. In the three-class model， Random Forest method performed best， with F1 score of 0.704 0 and AUC of 0.519 3 on the test set； while in the two-class model， CatBoost method performed optimally， with F1 score of 0.785 7 and AUC of 0.819 5 on the test set. CONCLUSIONS The constructed three-class model has the ability to predict excessive VPA blood concentration， but its prediction and model generalization abilities are poor； the constructed two-class model can only perform classification prediction for insufficient and normal blood concentration cases， but its model performance is stronger.

Objective To report the genetic analysis of a family with a fetus suspected of Ellis-van Creveld(EVC)syndrome based on ultrasound findings such as ventricular septal defect(VSD),short long bones in the limbs and polydactyly,and to conduct a literature review to clarify the pathogenic cause.Methods A 27-year-old pregnant woman,who was pregnant for the first time and had no prior deliveries,was admitted to the prenatal diagnosis center of Shijiazhuang Obstetrics and Gynecology Hospital in October 2021.At 17 weeks of gestation,ultrasound detected multiple fetal malformations.The genomic DNA of the fetal proband's amniotic fluid cells and the parents'peripheral blood samples were sequentially subjected to chromosomal karyotype analysis,chromosomal microarray analysis(CMA),and whole exome sequencing(WES).Suspected pathogenic mutations were verified by Sanger sequencing in the proband and its parents.Subsequently,a Minigene in vitro experiment was used to analyze one splicing mutation.Meanwhile,databases such as PubMed were searched,and literature reports were combined for genetic analysis.Results Chromosomal karyotype analysis of the fetus showed no abnormalities,and CMA did not detect any copy number variation(CNV)with clinical significance.WES results revealed two mutations in the EVC gene(NM_153717.2)of the fetus:a nonsense mutation c.1405G>T(p.E469X)in exon 10 and a splicing mutation c.1886+5G>A in intron 13.Family verification using Sanger sequencing showed that the father was a carrier of the c.1405G>T(p.E469X)mutation in exon 10,and the mother was a carrier of the c.1886+5G>A mutation in intron 13.The compound heterozygous mutation of the fetus was inherited from the parents.According to the guidelines of the American College of Medical Genetics and Genomics(ACMG)for classifying genetic variations,c.1405G>T(p.E469X)was classified as likely pathogenic mutation(PVS1+PM2),and c.1886+5G>A was classified as likely pathogenic mutation(PM2+PM3_Strong).The Minigene experiment results showed that the c.1886+5G>A mutation caused a 115-bp segment retention in intron 13,further supporting its pathogenicity.Review of the literature showed that the typical clinical manifestations of EVC syndrome include short limbs,short ribs,postaxial polydactyly,nail and tooth dysplasia,and congenital heart defects.Gene mutations in EVC/EVC2 were found to be the main pathogenic cause through whole exome sequencing,with mutation types including missense mutations,large-scale duplications/deletions,in-frame microdeletions,nonsense mutations,frameshift mutations,and splicing mutations.Conclusions The compound heterozygous mutations in the EVC gene are the pathogenic cause of the fetus.The detection of these mutations expands the genetic variation spectrum of Ellis-van Creveld syndrome.

Inhalation therapy,as a drug delivery method directly targeting the respiratory tract and lungs,has been widely used in the treatment of respiratory diseases due to its characteristics of efficient drug delivery,rapid onset,and low systemic side effects.However,traditional inhalation particles still have some limitations in drug stability,release control,and pulmonary delivery efficiency.In recent years,with the continuous development of biochemical materials,the performance of new inhaled particles has been significantly improved,which can provide better drug-loading capacity,more precise release control,and more efficient pulmonary delivery,showing great potential in improving drug efficacy and reducing side effects.This review comprehensively summarizes the classification,preparation techniques,and applications of inhalable particles.It further explores their prospects in precise therapy,personalized medication,and the next-generation drug delivery systems,aiming to promote research and technological innovation in inhalation therapy,ultimately advancing therapeutic solutions for respiratory diseases.

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.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Heart failure (HF) is a common end-stage clinical manifestation of cardiovascular diseases, imposing substantial health-related burdens worldwide. With its high mortality rates and poor long-term prognosis, there is a pressing need for novel therapies. SIRT1, a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase, has anti-cardiovascular aging properties and other cardioprotective effects, attracting much research attention in recent years. In addition, SIRT1 plays an important role in HF pathophysiology. This review summarized the roles of SIRT1 and its activators in HF, the changes of SIRT1 gene expression in cardiac tissues from animal models and HF patients, and the current status of clinical trials investigating SIRT1 activators as potential therapies for HF. This will provide new ideas for further exploration of pathological mechanisms and the development of clinical prevention strategies for HF.
Heart Failure/metabolism* ; Sirtuin 1/genetics* ; Humans ; Animals

This study explores the mechanism of Guben Jiannao Liquid on Alzheimer's disease(AD) by regulating autophagy based on the liver kinase B1(LKB1)/adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) pathway. Male SD rats were randomly divided into the blank group, model group, low-dose and high-dose groups of Guben Jiannao Liquid, and rapamycin group, with 10 rats in each group. Except for the blank group, all other groups of rats were injected bilaterally in the hippocampus with β-amyloid(Aβ)_(1-42) to establish the AD model. The low-dose(6.21 g·kg~(-1)) and high-dose(12.42 g·kg~(-1)) groups of Guben Jiannao Liquid and rapamycin group(1 mg·kg~(-1)) were given the corresponding drugs by gavage, and the blank and model groups were given an equal volume of saline by gavage for four weeks. Morris water maze was used to test the learning and memory ability of rats in each group; hematoxylin-eosin(HE) and Nissl staining were used to observe the morphological and quantitative changes of neurons and Nissl bodies in the CA1 region of rat hippocampus; immunohistochemistry was utilized to detect Aβ-positive cell expression in the CA1 region of rat hippocampus; transmission electron microscopy was employed to observe ultrastructural changes in rat hippocampal tissue, and Western blot was used to examine the protein expression levels of LKB1, p-AMPK/AMPK, p-mTOR/mTOR, Beclin1, p62, and LC3-Ⅱ in the hippocampal tissue of the rats. The results showed that compared with those in the blank group, rats in the model group had elevated evasion latency and decreased number of platform transversal and residence time in the platform quadrant. The number of neurons in the hippocampal area was reduced, and the morphology was impaired. The average integral optical density value of Aβ-positive cells was elevated; the expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were decreased, and the expression levels of p-mTOR/mTOR and p62 were increased. Compared with those in the model group, rats in the low-dose and high-dose groups of Guben Jiannao Liquid had shorter evasion latency, higher number of platform transversal, longer residence time in the platform quadrant, increased number of neurons, decreased expression of Aβ-positive cells and average integral optical density values, and increased number of autophagic lysosomes in hippocampal tissue. The expression levels of LKB1, Beclin1, and LC3-Ⅱ were elevated in the hippocampus of rats in the low-dose group of Guben Jiannao Liquid. The expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were elevated in the hippocampal tissue of rats in the high-dose group of Guben Jiannao Liquid, and the expression levels of p-mTOR/mTOR and p62 were decreased. The findings suggest that Guben Jiannao Liquid can improve cognitive impairment in AD rats, and its mechanism of action may be related to the activation of the LKB1/AMPK/mTOR signaling pathway and the up-regulation of autophagy level.
Animals ; Alzheimer Disease/physiopathology* ; Male ; TOR Serine-Threonine Kinases/genetics* ; Autophagy/drug effects* ; Rats, Sprague-Dawley ; Protein Serine-Threonine Kinases/genetics* ; AMP-Activated Protein Kinases/genetics* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; AMP-Activated Protein Kinase Kinases ; Humans ; Hippocampus/metabolism*