目的为了研究藏药八味沉香丸（Bawei Chenxiang Wan，BCW）防治心肌缺血的有效活性部位及机制。方法建立异丙肾上腺素（isoproterenol，ISO）诱导大鼠在体心肌缺血模型、冠脉结扎离体心脏缺血模型，评估BCW全方、醇提物及其不同极性萃取物对心电图ST段、心肌损伤、血流动力学及心肌梗死的影响。检测心肌组织磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase，PI3K）磷酸化水平、铜死亡相关蛋白的表达，以及Cu²⁺含量。利用氧糖剥夺（oxygen-glucose deprivation，OGD）心肌细胞损伤模型联合PI3K激动剂和抑制剂验证通路调控关系。结果BCW全方可改善心肌缺血大鼠心电图ST段抬高（P＜0.01），降低心肌损伤标志物含量，改善血流动力学，上调PI3K磷酸化水平（P＜0.01），减少Cu²⁺蓄积（P＜0.01），缩小心肌梗死范围。BCW醇提物及各萃取物可改善离体大鼠离体心肌缺血，减少Cu²⁺蓄积，其中BCW正丁醇萃取物效果较好（P＜0.01）；其可上调PI3K磷酸化水平（P＜0.01）、下调铁氧还蛋白还原酶（ferredoxin reductase 1， FDX1）（P＜0.05）、硫辛酸合酶（lipoic acid synthetase， LIAS）、二氢硫辛酰胺乙酰转移酶（dihydrolipoamide S-acetyltransferase， DLAT）多聚体表达（P＜0.05）。在OGD诱导心肌细胞模型中，PI3K激动剂可抑制DLAT多聚体表达（P＜0.05），而PI3K抑制剂可削弱正丁醇萃取物对DLAT多聚体的抑制作用（P＜0.05）。结论BCW正丁醇萃取物是改善大鼠心肌缺血的主要有效部位，其机制可能与PI3K激活介导的铜死亡抑制有关。
目的探讨依托咪酯列管后广西涉依托咪酯刑事案件的特征。方法收集2023年10月至2025年7月期间在中国裁判文书网上公布的广西涉依托咪酯刑事案件文书资料，提取人口学、犯罪学与法医毒物学特征，分析罪犯人口学特征与广西一般人群基准的差异，以及年龄、文化程度、前科和就业情况与犯罪类型之间的联系。结果共纳入51个判决案件，含174名涉案人员。罪犯以男性、青年、低学历、有违法犯罪前科、无业为主，在性别、年龄、文化程度及就业情况四个维度上与广西一般人群基准的差异均有统计学意义（均P＜0.01）。主要犯罪类型为容留他人吸毒罪和贩卖毒品罪，案件参与模式主要为多人共同涉案，以电子烟及其制品为主要毒品载体，法医检测结果揭露涉案人员存在依托咪酯与氯胺酮混合滥用。前科情况与犯罪类型选择存在统计学关联（Fisher’s P＝0.006）。有前科者以单一类型犯罪为主，而无前科者在复合型犯罪中相对有前科者占比更高。结论依托咪酯列管后，广西涉依托咪酯刑事案件犯罪人群特征为低学历、低就业、高前科。犯罪手段呈现隐蔽化、犯罪形态呈现群体化、毒品滥用呈现混合倾向。建议加强监测高危人群，升级毒物检测技术体系，以应对新型毒品引发的问题。
目的探讨环保型试剂与传统试剂在组织处理、组织切片、苏木精-伊红（HE）染色、特殊染色及免疫组化中的应用效果。方法选取小鼠及新西兰兔的胰腺、肾脏、脾脏、肝脏、肺、骨骼肌、心脏组织，随机分为传统组（A组）、环保试剂Ⅰ组（B组）、环保试剂Ⅱ组（C组）。对三组组织处理后进行石蜡切片、HE染色、磷钨酸苏木素染色、Mallory三色染色，胰腺组织切片进行免疫组化检测胰岛素蛋白。评估指标包括：组织形态完整性、包埋操作性、切片质量以及染色效果。结果三组样本在固定效果、包埋操作、切片质量等方面无明显差异。经HE染色后，各组组织核质染色鲜艳、对比清晰，优良率分别为A组98%、B组99%、C组97%，差异无统计学意义（A vs. B，P=0.561；A vs. C，P=0.651）。在磷钨酸苏木素染色中，A组和C组的横纹肌及胶原纤维结构对比清晰、染色鲜艳，B组存在染色不均等问题。优良率分别为A组100%、B组10%、C组95%，A组与B组差异有统计学意义（P＜0.01），A组与C组差异无统计学意义（P=0.311）。在Mallory三色染色中，A组和B组的效果优于C组。优良率分别为A组95%、B组90%、C组15%，A组与C组差异有统计学意义（P＜0.01），A组与B组差异无统计学意义（P=0.548）。免疫组化结果显示，A组背景干净，无非特异性染色，B组和C组存在明显的非特异性染色，组间非特异性染色率差异有统计学意义（A vs. B，5% vs. 100%，P＜0.01； A vs. C，5% vs. 100%，P＜0.01）。结论在HE制片中，环保型试剂的组织固定效果良好，HE染色效果与传统试剂的相当，能满足教学的需求。特殊染色中，B组、C组分别在Mallory三色染色、磷钨酸苏木素染色中的表现较佳。但环保型试剂在免疫组化中存在非特异性问题，有待进一步优化。
Parkinson's disease(PD)is a central neurodegenerative disorder with insidious onset and slow progression.It is pathologically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta and the abnormal aggregation of α-synuclein(α-Syn),resulting in the formation of Lewy bodies.These pathological changes give rise to motor dysfunction,sleep disturbances,cognitive impairment,and other symptoms,thereby markedly reducing patients'quality of life.Current treatments remain largely symptomatic,including dopaminergic replacement therapy and deep brain stimulation(DBS),while long-term adverse effects and declining efficacy in advanced stages remain unresolved.Therefore,the development of disease-modifying therapies capable of delaying or reversing disease progression is of critical importance.Aquaporin-4(AQP4)is the most abundant water channel in the brain and is predominantly expressed in astrocytic endfeet,where it plays a key role in maintaining cerebral water homeostasis,blood-brain barrier integrity,and glymphatic waste clearance.Recent studies have demonstrated that both the expression level and polarization of AQP4 are altered in PD animal models and in brain tissues from patients with PD,and these alterations are closely associated with glymphatic dysfunction,impaired α-Syn clearance,disruption of central nervous system homeostasis,and activation of neuroinflammation.Following the cascade of"AQP4 alteration-impaired glymphatic clearance-α-Syn deposition-neuroinflammation-PD progression",this review outlines the basis of AQP4 polarization and glymphatic function,summarizes the potential mechanisms by which AQP4 abnormalities promote α-Syn accumulation and inflammatory amplification,and synthesizes current clinical evidence and therapeutic advances.Nevertheless,inconsistencies across experimental models and PD subtypes remain,and the causal role of AQP4 as well as population heterogeneity has yet to be fully elucidated.Future large-scale,long-term,subtype-stratified studies are warranted to explore precise regulatory strategies targeting AQP4 and to validate its safety and efficacy as a novel disease-modifying therapeutic target for PD.
目的为了探究狂犬病毒糖蛋白（RVG）修饰的间充质干细胞外泌体对强迫症小鼠模型的治疗效果，明确外泌体治疗强迫症的疗效以及探究其发挥作用的机制。方法提取原代小鼠脂肪来源的间充质干细胞，使用病毒感染获得过表达RVG的间充质干细胞外泌体，并通过粒径分析、Western blot、透射电镜表征外泌体。利用喹吡罗构建强迫症小鼠模型，将小鼠分为5组：对照组、模型组、氯米帕明（CMI）组、间充质干细胞外泌体（MSC-EXO）组、RVG修饰的间充质干细胞外泌体（RVG-MSC-EXO）组，并通过行为学实验如强迫检查、旷场、埋珠、水迷宫测试小鼠强迫、认知等行为。通过qPCR、ELISA检测小鼠前额叶皮质炎症因子水平，并通过免疫荧光检测小鼠前额叶皮质小胶质细胞极性。通过小动物活体成像（IVIS）验证RVG-MSC-EXO在小鼠体内靶向性。结果过表达RVG的间充质干细胞外泌体对小鼠脑部具有靶向性。喹吡罗小鼠模型经过外泌体治疗后，强迫检查和埋珠行为改善，促炎因子减少、抗炎因子增加。外泌体治疗后喹吡罗模型小鼠前额叶皮层小胶质细胞极性由M1型转变为M2型。结论过表达RVG的间充质干细胞外泌体可靶向小鼠大脑，通过转变小胶质细胞极性以改善强迫症小鼠颅内炎症水平，最终减少强迫症小鼠的强迫样行为。
目的评估6种胰岛素抵抗（IR）替代指标对于心血管-肾脏-代谢综合征（CKM）0-3期成人心血管疾病（CVD）风险的预测价值。方法分析中国健康与退休纵向研究 （CHARLS）中6 813名参与者的相关资料。采用Cox 比例风险和限制性立方样条（RCS）模型评估IR替代指数（TyG、TyG-BMI、TyG-WC、TyG-WHtR、TyG-CVAI、CVAI）与CVD发生率之间的关联。采用受试者工作特征曲线（ROC）评估区分能力，净重新分类改善指数（NRI）评估增量预测价值，决策曲线分析（DCA）评估临床效用，从3个维度综合比较6种指标的预测效能。结果6种IR替代指标均能预测CKM人群中的心血管疾病发生率。RCS回归分析显示，各指标与CVD发生率均呈线性关系。ROC曲线分析显示，CVAI的AUC值最高（0.628，95%CI： 0.611-0.646），显著优于单一TyG指数（P=0.001 6）。NRI分析表明，CVAI对事件组的重新分类改善效果显著（事件NRI=0.042 8）。DCA结果显示，CVAI在多数临床阈值下获得最高的净获益。亚组分析进一步证实，CVAI在CKM 2-3期人群中与CVD风险的关联更强。结论这6种IR替代指数是预测CKM 0-3期人群CVD发病率的宝贵工具。其中，CVAI对CKM 1-3期成人未来的CVD风险具有最优的预测价值。
目的探讨不同剂量的二型抗性淀粉生玉米淀粉（UCCS）对小鼠肠道黏膜屏障功能的影响及潜在机制。方法将20只C57BL/6小鼠随机分为4组，对照组（普通饲料）及UCCS低（188.8 g/kg）、中（314.8 g/kg）、高（440.6 g/kg）剂量组。实验期间动态监测小鼠体质量及疾病活动指数（DAI）。8周后测量结肠长度；HE染色观察病理变化并计算炎症评分；免疫荧光法检测紧密连接蛋白ZO-1、E-钙黏蛋白及Villin的表达与共定位；ELISA法检测血清炎症因子（IL-6、TNF-α、IL-1β、MIP-1α/CCL3）及粪便钙卫蛋白含量；16S rRNA测序分析肠道菌群结构及功能预测。结果与对照组相比，各UCCS组小鼠结肠长度显著缩短（P=0.000 5），炎症评分显著增高（P=0.013 3）。免疫荧光显示，UCCS组结肠黏膜ZO-1与Villin的表达及共定位阳性细胞数均显著下降（均P＜0.05）。血清IL-6（P=0.006 4）、TNF-α（P=0.000 1）、IL-1β（P=0.001 4）、MIP-1α/CCL3（P＜0.000 1）水平显著升高，粪便钙卫蛋白在干预早期（1~2周）显著升高（P＜0.05）。16S rRNA测序表明，UCCS干预显著改变了肠道菌群的β多样性（P＜0.05）。其中，UCCS组产丁酸的梭菌纲UCG-014（Clostridia_UCG-014）的相对丰度显著富集，条件致病菌脱硫弧菌（Desulfovibrio）的丰度也呈现不同程度的富集。与免疫调节相关的阿克曼氏菌属（Akkermansia）和杜博西菌属（Dubosiella）丰度降低。PICRUSt2功能预测分析显示，UCCS干预影响了肠道菌群的能量代谢、抗氧化及硫循环等多种功能。结论UCCS可能通过干扰肠道菌群稳态及代谢平衡，诱发肠道炎症反应并损伤肠黏膜屏障功能。本研究提示，在应用UCCS时应关注其剂量相关的肠道损伤风险。
目的总结儿童对缓释型促性腺激素释放激素类似物（GnRHa）的药物超敏反应的发生率、临床特征，为儿童GnRHa的安全临床应用提供指导。方法通过回顾分析1990.1~2023.7在中山大学附属第一医院儿童生长中心就诊并接受GnRHa治疗的中枢性性早熟（CPP）或快速进展型早发青春期（EFP）的患儿病史资料，总结GnRHa相关药物超敏反应的发生情况，总结全身/系统性超敏反应、无菌性脓肿病例的发生率、临床特征。结果接受GnRHa治疗的CPP/EFP患儿有1 684例，女∶男=3.8∶1。有9例（0.53%）患儿出现了44例次药物超敏反应，无菌性脓肿4例（0.24%），共21例次；系统性超敏反应5例（0.30%），共14例次。有4例患儿对醋酸曲普瑞林发生超敏反应；3例对醋酸亮丙瑞林发生超敏反应；2例对醋酸曲普瑞林和醋酸亮丙瑞林均发生超敏反应。其中醋酸亮丙瑞林主要超敏反应为局部迟发性无菌性脓肿，有4例（4/277，1.44%）；醋酸曲普瑞林引发的超敏反应主要为全身/系统性超敏反应，有5例（5/1 501，0.33%）。病例1病情较为严重且复杂，不仅对多种GnRHa剂型发生超敏反应（缓释型曲普瑞林、缓释型亮丙瑞林、短效曲普瑞林），且临床表现多样，有硬结、无菌性脓肿、系统性超敏反应，甚至出现下丘脑-垂体-性腺轴功能失抑制，导致治疗失败。结论接受缓释型GnRHa治疗的儿童出现药物超敏反应的比例相对低，发生率为0.53%，临床表现多样，主要表现为无菌性脓肿和系统性超敏反应，严重者可致下丘脑-垂体-性腺轴失抑制导致治疗失败。
[Objective]To investigate the role and related mechanisms of mast cells(MCs)in alcoholic cardiomyopathy(ACM).[Methods]An ACM model was established in C57BL/6 mice by feeding them with alcohol liquid diet,and some model mice were intervened with cromolyn sodium,a mast cell stabilizer.Cardiac function,myocardial remodeling and the expression of related proteins were evaluated by echocardiography,tissue staining and Western blot.In vitro,neonatal rat ventricular cardiomyocytes(NRVCs)were stimulated with mast cell granules(MCGs)and/or alcohol,and pathway inhibitors were used to explore the underlying mechanisms.[Results]Long-term alcohol feeding caused significant cardiac dysfunction and mast cells activation in mice,accompanied by increased expressions of chymase,NOX2,NOX4 and apoptosis-related protein cleaved Caspase-3(c-Caspase3)in myocardial tissues(P＜0.05).Pretreatment with cromolyn sodium improved cardiac function,inhibited mast cell activation,and reduced the expressions of the above proteins.In vitro experiments showed that treatment with MCGs or alcohol alone up-regulated the expressions of c-Caspase3,NOX2,NOX4 and phosphorylated PKCβ1(p-PKCβ1)in cardiomyocytes,and the combined stimulation of the two had a synergistic effect.Protease-activated receptor 2(PAR2)inhibitor down-regulated the MCG-induced expressions of the above proteins.PKCβ1 inhibitor also inhibited the MCG-induced expressions of c-Caspase3,NOX2 and NOX4.Chymase inhibitor exerted a partial inhibitory effect on MCG-induced cardiomyocyte apoptosis.[Conclusion]During the development of ACM,mast cells are activated,and the released MCGs may promote cardiomyocyte apoptosis through the PAR2-PKCβ1-NOX2/NOX4 signaling pathway,in which chymase plays an important role.
Chronic excessive alcohol consumption is a major global public health concern that severely endangers human health.Excessive alcohol intake disrupts the functions of multiple organs and systems in the human body through diverse mechanisms.The alcohol-sensitive microbiota-gut-brain axis plays a critical role in maintaining systemic homeostasis,immune maturation,and endocrine metabolism.Chronic excessive alcohol consumption not only alters the composition of the gut microbiota and the levels of its metabolites,but also compromises intestinal barrier integrity,increases intestinal permeability,and allows harmful metabolites to enter the systemic circulation,thereby triggering a variety of diseases including alcohol-related brain injury.Alcohol-related brain injury is one of the most severe consequences of unrecognized or inadequately treated alcohol use disorder(AUD),which can lead to extensive neuronal damage and neurocognitive dysfunction.Although the potential role of the microbiota-gut-brain axis in alcohol-related brain injury has been proposed,the exact underlying mechanisms have not yet been fully elucidated.Therefore,in this review,we systematically analyze the associations among chronic excessive alcohol consumption,the microbiota-gut-brain axis,and alcohol-related brain injury,and explore the potential mechanisms underlying alcohol-induced brain damage via this axis.
目的探讨中晚期肝细胞癌（HCC）患者经动脉化疗栓塞（TACE）联合靶免治疗后肠道菌群组的特征及与预后的关联。方法本研究回顾性收集2025年2月至2025年7月就诊中山大学附属第一医院并接受过TACE联合靶免治疗的中晚期肝细胞癌患者临床资料，采集患者本次入院治疗前的粪便样本。根据无进展生存期（PFS）是否达到6个月，分为预后好组与预后差组；按照修正后实体瘤疗效评价标准（mRECIST）评估首次TACE术后是否缓解，分为应答组与无应答组。采用宏基因组测序技术对粪便菌群测序，通过生信分析判断两组肠道细菌与真菌群落的多样性、组成差异，筛选预后相关的特征性菌群。结果共计61例患者符合标准。α多样性及β多样性分析，两种分组方式组间细菌、真菌多样性均无统计学差异（P＞0.05）。在细菌层面，约氏乳杆菌（预后分组P=0.048，应答分组P=0.043）、齿双歧杆菌（预后分组P=0.004，应答分组P=0.030）和艰难梭菌（预后分组P=0.017，应答分组P=0.016）在预后好组和应答组中均显著富集。真菌层面，十齿隐球菌（P=0.045）、条锈菌（P=0.002）、嗜树克沃尼埃拉菌（P=0.015）在预后好组中富集；叶斑病菌（P=0.037）在应答组中富集；毒蝇钩霉菌（P=0.024）在无应答组中富集。按照两种分组的共同差异菌丰度分别进行生存分析，结果显示齿双歧杆菌的丰度与患者预后存在显著关联。结论肠道菌群的差异同中晚期肝癌TACE联合靶免治疗的预后相关，齿双歧杆菌可能作为评估联合治疗疗效的潜在预测指标或影响其疗效的潜在干预途径。肠道真菌群的差异可能与中晚期肝癌TACE联合靶免治疗的预后相关。
Upper limb motor impairment is a common sequela of stroke and significantly compromisses patients'activities of daily living and quality of life.Non-invasive vagus nerve stimulation(nVNS),developed from conventional vagus nerve stimulation(VNS),is a safer,more convenient,and cost-effective neuromodulation technique with the adventage of avtive regulation,It has been increasingly applied in clinical practice and neuroscience research,and its therapeutic potential in post-stroke upper limb rehabilitation has been preliminaruly demonstrated.This systematic review comprehensively examines the mechanistic basis and clinical advancements of nVNS in treating upper limb motor dysfunction following stroke,with a particular focus on the International Classification of Functioning,Disability and Health(ICF)framework.From the perspectives of body function,individual activity,and social participation,the rehabilitative effects of nVNS are analyzed in an integrated manner.Specifically,nVNS enhances neural plasticity,mitigates inflammatory responses,and improves cerebral perfusion in ischemic regions by modulating the secretion of neurotransmitters such as norepinephrine,acetylcholine,and γ-aminobutyric acid,thereby promoting neurological recovery at the body function level.Moreover,the synergistic application of nVNS with rehabilitative training has been shown to sustainably improve motor function and activities of daily living,yielding functional benefits that extend to the levels of individual activity and social participation.Building upon this foundation,the present study examines the technical challenges confronting nVNS and proposes future research trajectories focusing on parameter optimization,multimodal neuromodulation integration,and rehabilitation for lower limb dysfunction.These directions aim to facilitate precision personalized therapeutics for stroke patients.
The integrity of the intestinal barrier is the basis of physiological function of the intestine,which is essential for maintaining nutrient absorption,antigen exclusion,and immune homeostasis.High-altitude environments are characterized by hypobaric hypoxia and are often complicated by combined stresses such as cold,intense ultraviolet radiation,increased physical exertion,dehydration,and dietary changes.These factors may lead to synergistic dysfunction of the mechanical,chemical,immune,and biological barriers of the intestine,thereby inducing local or systemic inflammatory responses.Current evidence indicates that high-altitude-related intestinal barrier injury is not driven by a single pathway but is co-mediated by multiple factors:aberrant activation of hypoxia-inflammation signaling pathways,including hypoxia-inducible factor-1α(HIF-1α)and nuclear factor-κB(NF-κB);synergistic enhancement of Notch and Wnt/β-catenin signaling pathways leading to goblet cell reduction and insufficient mucin 2(MUC2)secretion;imbalance of T helper 17/regulatory T cells(Th17/Treg)and activation of the NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome;as well as gut microbiota dysbiosis and weakened protective effects of short-chain fatty acids(SCFAs).This article systematically reviews the molecular mechanisms underlying high-altitude-induced intestinal barrier injury,and proposes a multi-mechanism synergistic model under the"adaptation-decompensation"framework on this basis.Combined with scenarios of acute high-altitude exposure,it summarizes the evidence progress and limitations of intervention strategies of ameliorating intestinal barrier injury,aiming to provide a theoretical basis and practical reference for the prevention and intervention of high-altitude-related intestinal injury.
目的比较广州市某三甲医院临床感染来源与医院环境来源鲍曼不动杆菌（AB）在分子流行病学特征、耐药性、消毒剂耐受性、毒力及相关基因分布、质粒流行特征等方面的差异，评估环境菌株与临床菌株的关联性及环境污染的潜在传播风险。方法收集2024—2025年广州市某三甲医院118株临床来源及102株医院环境来源的AB。采用质谱及16S rRNA测序鉴定菌种；琼脂稀释法测定8种抗菌药物的最小抑菌浓度（MIC）；结晶紫染色法评估生物膜形成能力；大蜡螟感染模型评价菌株毒力；通过全基因组测序进行多位点序列分型（MLST）、系统发育分析、耐药、耐消毒剂和毒力基因分布并进行质粒筛选。结果220株AB共鉴定出38种已知ST型，以ST2和ST40为优势谱系。药敏试验显示，临床感染组对米诺环素（MC）、亚胺培南（IMP）等抗生素的耐药水平，以及三氯生（TCS）和苯扎溴铵（BAB）消毒剂的耐受水平均普遍高于环境来源组（P＜0.001），且blaOXA-23、adeB等耐药基因检出率均超过70.0%。统计学评价证实，TCS与BAB的MIC值同多种抗生素耐药表型呈显著正相关（P＜0.05）。生物膜实验中，环境来源组中强成膜菌株的比例（64.7%）显著高于临床感染组（11.9%；χ²=69.06，df=2，P＜0.000 1），且菌株致死率随成膜能力增强而提高。此外，共检出41个质粒谱系及219种插入序列（IS），IS1006及IS1007等IS与blaOXA-23及katA等耐药、毒力基因存在高频共现。结论该三甲医院AB的优势谱系为ST2与ST40。临床感染组的抗生素耐药性和消毒剂的耐受水平普遍高于环境来源组，环境来源组强生物膜形成能力更突出，临床感染组则以弱的优化及多重耐药菌的分子流行病学监测提供参考。
目的鉴定可能有助于优化伴门静脉癌栓（PVTT）肝细胞癌免疫治疗策略的关键配体-受体作用轴。方法从基因表达综合数据库（GEO）下载正常组织（Norm）和PVTT组织的单细胞转录组测序数据，并进行整合分析与细胞注释。采用CellChat推断细胞间通讯网络并比较信号通路活性，从而筛选差异显著的候选配体-受体作用轴。随后，利用多重免疫荧光（mIF）在组织水平评估候选作用轴相关信号的空间分布特征。在细胞水平上，进一步通过qPCR和流式细胞术检测外周血来源CD8+ T细胞及人肝星状细胞系LX-2中关键配体和受体的表达情况。最后，结合重组蛋白刺激以及拮抗剂或中和阻断实验，对其功能效应进行体外验证。结果分析结果显示，在PVTT中，CD8+ T细胞与活化肝星状细胞（aHSCs）之间存在显著的双向通讯。由CD8+ T细胞指向aHSCs的通讯中，SPP1-CD44轴最为突出；而在相反方向上，MIF-（CD74+CD44）轴获得了较强支持。上述两条作用轴均在生物信息学筛选、组织空间定位分析以及细胞与功能实验验证中得到一致支持。结论SPP1-CD44轴和MIF-（CD74+CD44）轴可能通过促进间质活化及诱导T细胞功能重塑，共同参与塑造PVTT的免疫抑制性肿瘤微环境（ITME），并有望成为提高PVTT患者免疫治疗应答的潜在干预靶点。
目的本研究旨在融合多种易获取的临床数据与二维常规超声图像，构建用于评估脂肪性肝病（SLD）不同严重程度的深度学习神经网络模型。方法回顾性收集649例行超声衰减成像（ATI）检查患者的临床数据和超声图像，以ATI作为参考标准，将患者分为正常（S0）及轻（S1）、中（S2）、重度（S3）脂肪肝4组，按8∶2比例随机划分为训练集和验证集。采用对比语言-图像预训练（CLIP）模型提取临床与图像多模态特征，并分别训练随机森林（RF）和多层感知器（MLP）模型。在验证集中对比多模态模型与单一模态的诊断性能。结果与RF模型相比，MLP模型表现更优［AUC（95%CI）：S0=0.96 （0.93～0.99），S1=0.99（0.96～1.00），S2=0.75 （0.64～0.82），S3=0.88 （0.81～0.93）］。相较于单模态模型［仅临床数据AUC（95%CI）：0.89 （0.81～0.95）、0.69 （0.52～0.79）、0.64 （0.43～0.67）、0.80 （0.73～0.90）；仅图像数据AUC（95%CI）：0.91 （0.86～0.96）、0.89 （0.67～0.89）、0.69 （0.58～0.78）、0.86 （0.82～0.94）］，图像‑临床数据融合模型在各分级上均表现出显著更优的性能。精确率、召回率、F1分数、F2分数、混淆矩阵与损失函数学习曲线进一步证实，多模态数据融合可显著提升整体训练与预测效果。结论本研究构建的基于CLIP的MLP多模态分类模型可有效实现脂肪肝严重程度的自动分级，证实了融合临床与超声数据在脂肪肝精准分级的显著优势，为慢性脂肪肝病的临床管理提供准确、可靠的辅助评估工具。
目的探讨内脏脂肪代谢评分（METS-VF）与老年人群心血管代谢共病（CMM）及认知功能的关联，揭示METS-VF作为评估工具在老年人群体中的作用，并为CMM和认知功能的早期筛查及干预策略提供依据和新视角。方法本研究基于湖北老年记忆队列（HMACS）的横断面数据，纳入60岁及以上老年人，计算METS-VF指数并进行四分位分组（Q1-Q4）。通过问卷调查评估CMM（糖尿病、心脏病、中风中至少两种共存），并采用标准化认知测试评估总体认知、记忆、语言、执行功能和注意力。采用Logistic和Linear回归分析METS-VF与CMM患病风险及认知功能之间的关联性，采用限制性立方样条检验剂量-反应关系，亚组分析评估METS-VF在不同群体中的差异性，并采用多分类无序Logistic回归评估METS-VF与CMM患病模式的表现。结果共纳入3 790名≥60岁的老年参与者。校正混杂因素后，与最低四分位组Q1组相比，Q4组METS-VF与更高的CMM患病风险相关［OR=3.00，95%CI （2.18，4.16）］，且与更低的总体认知［b=-0.12，95%CI （-0.21，-0.04）］、注意［b=-0.14，95%CI （-0.24，-0.05）］和执行功能［b=-0.10，95%CI （-0.20，-0.00）］得分相关。剂量-反应分析未显示出METS-VF指数与CMM或认知功能的非线性关系（P for nonlinear>0.05）。亚组分析显示，高METS-VF指数的男性群体中的总体认知得分更低，而女性群体中执行功能得分更低（P for interaction均＜0.05）。多分类无序Logistic回归分析显示，METS-VF指数与糖尿病合并冠心病［OR=2.62，95%CI （1.66，4.15）］或中风［OR=2.66，95%CI （1.73，4.09）］的患病风险增加相关，尤其在糖尿病同时伴随中风和冠心病的组别中，METS-VF与患病风险的关联最强。结论METS-VF升高与老年人群更高的CMM患病率及更低的总体认知、注意和执行功能得分相关，糖尿病可能是多病共存模式的关键驱动因素，METS-VF指数可作为筛查心血管代谢风险和评估认知功能的双用途工具。
目的基于O-RADS构建并评估融合超声造影（CEUS）及标准化z值的卵巢恶性肿瘤风险预测模型（ROMA z-score）的多参数诊断模型，以期提升对良性、交界性和恶性卵巢上皮性肿瘤（OETs）的三分类诊断准确性。方法本研究回顾性纳入2018年5月至2024年12月经病理确诊的129例卵巢上皮性肿瘤患者。收集患者临床资料（包括年龄、绝经状态、体质量指数、HE4、CA125）及超声影像资料（常规超声特征与超声造影特征）。根据病理结果将肿瘤分为良性、交界性及恶性三类。采用随机森林算法构建预测模型，并绘制ROC曲线将O-RADS联合超声造影（O-RADS+CEUS）、O-RADS联合ROMA z-score（O-RADS+ROMA z-score）、三者联合（O-RADS+CEUS+ROMA z-score）与O-RADS的诊断效能进行比较。结果本研究共纳入129例OETs患者，其中良性63例，交界性25例，恶性41例。与O-RADS相比，3个参数联合（O-RADS+CEUS+ROMA z-score）诊断效能最佳，其鉴别良性与交界性肿瘤的曲线下面积（AUC）为0.87（95%CI：0.79-0.95）vs. 0.64（95%CI：0.51-0.76），P＜0.001）；鉴别交界性与恶性肿瘤的AUCs为0.90（95%CI：0.83-0.97）vs. 0.64（95%CI：0.50-0.78），P＜0.001。随机森林模型分析显示，HE4、CA125和超声造影特征是预测价值最高的变量，其在总体重要性评分（51.94分）中分别占11.02分、8.82分与18.10分。测试队列中该模型的总体诊断准确率为72.97%，曲线下面积为0.89（95%CI：0.77-1.00），敏感性为67.06%，特异性为85.01%。结论基于O-RADS联合超声造影与ROMA z-score的多参数模型在鉴别良性与交界性OETs及交界性与恶性OETs中表现出最高的诊断效能。人附睾上皮分泌蛋白4、糖类抗原125及超声造影特征为关键预测因子，支持模型在完善OETs术前风险分层中的作用。
[Objective]To investigate early nutrition and growth of preterm monochorionic diamniotic(MCDA)twins combined with selective intrauterine growth restriction(sIUGR)and explore the potential role of DNA methylation in regulating extrauterine growth.[Methods]Twenty-four pairs of preterm MCDA twins combined with sIUGR hospitalized in the Department of Neonatology of The First Affiliated Hospital of Sun Yat-sen University from March 2019 to February 2022 were enrolled,divided into larger twins group(n=24)and smaller twins group(n=24)according to birth weight.The comparison of daily nutritional intakes,the incidence of neonatal complications and physical growth from birth to 24 months of corrected age between two groups was performed using t-test,analysis of ANOVA,Chi-square test or Fisher's exact test.Differential DNA methylation analysis was performed using the methylation microarrays and differentially methylated site was validated using pyrosequencing method.[Results]There were no significant differences in the daily intake of carbohydrate,protein,fat and energy between two groups(all P＞0.05).There were no significant differences in the incidence of asphyxia,neonatal respiratory distress syndrome,bronchopulmonary dysplasia,retinopathy of prematurity and necrotizing enterocolitis between two groups(all P＞0.05).Z-scores for weight,length and head circumference were significantly lower in the smaller twins group compared with the larger twins group from birth to 24 months of corrected age(all P=0.000).Difference in Z-scores for weight and length at term,6 months,12 months of corrected age did not differ significantly from that at birth(all P＞0.05)while difference in Z-scores for weight and length between the twins at 18 months and 24 months of corrected age were significantly lower than that at birth(P=0.009,P=0.032,P=0.026,P=0.004).Difference in Z-scores for head circumference at 6 months,12 months,18 months,24 months of corrected age were significantly lower than at birth(P=0.001,others P=0.000)except at term(P＞0.05).The differences in weight,length and head circumference between the twins at term,6 months,12 months,18 months and 24 months of corrected age significantly reduced(P=0.001,P=0.007,P=0.001,others P=0.000).Eighteen differentially methylated sites were identified and the methylation level of NFATC1 gene in the smaller twins group was significantly higher than that in the larger twins group(P=0.043).[Conclusion]MCDA twins combined with sIUGR shares similar early nutrition and neonatal complications,while smaller twins at 24 months of corrected age grow faster than larger twins,which might be related to a higher methylation level of NFATC1 gene in smaller twins.
目的为了提升胎儿股骨短小（FL）的遗传学病因诊断水平，探讨全外显子组测序（WES）与染色体异常检测联合应用在产前诊断中的价值。方法选取2023年11月至2025年5月于中山大学孙逸仙纪念医院深汕中心医院产前诊断与医学遗传中心就诊的27例孕中晚期股骨短小胎儿［FL＜同孕周第5百分位数或＜-2标准差（SD）］为研究对象，采集羊水或脐血样本并行染色体核型分析（19例）、染色体微阵列分析（CMA）或低深度全基因组测序（CNV-seq）（27例），并开展家系三重全外显子组测序（Trio-WES）（27例）。检测结果依据美国医学遗传学与基因组学学会（ACMG）指南进行致病性解读。结果27例胎儿中，共17例检出26个基因组变异，包括染色体数目异常（嵌合型）、拷贝数变异（CNV）、单核苷酸变异（SNV）和插入缺失（INDEL）。其中11例病例检出的基因组变异可解释股骨短小的表型，总体诊断率为11/27，其中致病/疑似致病变异解释9例，意义不明变异（VUS）解释1例，另外染色体核型分析发现染色体数目异常（嵌合型）解释1例。CNV检测（CMA/CNV-seq）诊断率为2/27，WES诊断率为10/27，并在CNV检测阴性或意义不明病例中额外提升诊断率8/27。检出变异包括FGFR3、SHOX、DUOX2、CLCN5及HBA1/HBA2等基因相关致病突变。结论Trio-WES检测可显著提高胎儿股骨短小的遗传学诊断率，尤其适用于常规染色体检测无法明确病因的病例。核型分析仍具备检测低比例嵌合的染色体大片段异常的能力，可对WES及CNV检测形成有效补充。推荐在产前诊断中采用阶梯式或并行遗传检测策略，以优化诊断效能与临床决策支持。
