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关键词： colitis   dealcoholized muscadine wine   diet-gene interactions   gut microbiome   IL-10−/− mice  

摘要： Background/Objectives: Colitis is a chronic condition affecting millions worldwide. Purple muscadine wine polyphenols have a unique composition and possible disease-preventive properties. This study aims to determine how dealcoholized muscadine wine (DMW) affects the development of colitis and gut microbiome in IL-10^−/− mice, compared to wild types (WT). Methods: Six-week-old male IL-10^−/− and WT C57BL/6 mice were fed either a DMW-supplemented diet (4.8% v/w) or a control diet based on AIN-93M for 154 days. Colitis severity was evaluated by disease activity, intestinal permeability, gene expression of cytokines and tight junction proteins in the colon, and inflammatory cytokines in the serum. Fecal samples were collected for gut microbiome profiling via 16S rRNA gene sequencing. Results: DMW contained predominantly anthocyanins and a significant amount of ellagic acid. IL-10^−/− mice developed mild colitis as indicated by the disease activity index. DMW × gene interactions decreased intestinal permeability, colonic mRNA levels of IL-1β, and serum TNF-α in the IL-10^−/− mice. DMW suppressed the colonic mRNA levels of IL-6, enhanced the gene expression of ZO-1, but did not influence the mRNA level of TNF-α or occludin. While DMW did not alter α-diversity of the gut microbiome, it significantly influenced β-diversity in the WT mice. DMW significantly reduced the relative abundances of Akkermansia in the IL-10^−/− and WT mice. DMW and DMW×gene interaction decreased the relative abundance of Parasutterella only in IL-10^−/− mice. Conclusions: These results suggested that polyphenols from DMW interacted with genes to moderately alleviate the development of colitis in IL-10^−/− mice and could be a useful dietary strategy for IBD prevention. © 2025 by the authors.

摘要： BackgroundInvasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer after invasive ductal carcinoma of no special type (NST), accounting for 10-15% of diagnoses. Despite the myriad molecular, histological and clinical differences between ILC and NST tumors, patients are treated in the same way, and although prognosis initially is good, ILC patients have poorer long-term outcomes. Understanding the differences between these two subtypes and identifying ILC-enriched therapeutic targets is necessary to improve patient *** and mouse cancer-associated fibroblasts (CAFs), ILC cell lines and patient-derived organoids were used for in vitro and in vivo studies, including western blotting, migration, organotypic invasion assays and dissemination in zebrafish embryos. RNASeq was used to identify CAF and interleukin-6 (IL-6)-derived gene signatures. Bioinformatic analysis of public databases and immunohistochemical of human tumor microarrays was carried *** identified IL-6 as a paracrine CAF-derived factor that activates Signal-Transducer-and-Activator-of-Transcription-3 (STAT3) in human and mouse ILC models. Analysis of human breast tumors showed that the IL-6/JAK/STAT3 pathway is enriched in ER + ILC compared to ER + NST. A 42-gene CAF dependent IL-6 gene signature and 64-gene consensus IL-6 gene signature were generated and were significantly enriched in ER + ILC, with many of the genes overexpressed in ILC tumors. IL-6 treatment suppressed downstream estrogen signaling and also led to the acquisition of a more mesenchymal-like phenotype associated with increased migration and invasion. Finally, IL-6 treatment significantly increased ILC cell dissemination following injection into zebrafish ***-derived IL-6 drives paracrine activation of the IL6/JAK/STAT3 signaling pathway which is enriched in ILC. This leads to the acquisition of pro-tumorigenic phenotypes, highlighting the pathway as a poten

关键词： 急性胰腺炎   葡萄糖与淋巴细胞比值   三酰甘油-葡萄糖指数  

摘要： 目的 分析葡萄糖与淋巴细胞比值(GLR)、三酰甘油-?葡萄糖(TyG)指数与急性胰腺炎(AP)病情严重程度的关联及对疾病严重程度的预测价值,为临床AP严重程度的评估提供参考依据。方法 回顾性分析蒙城县第一人民医院2021年10月至2023年8月收治的86例AP患者的临床资料,根据AP严重程度床边指数(BISAP)将患者分为高危组(29例,≥3分)和低危组(57例,<3分)。比较两组患者的一般资料、GLR及TyG指数;采用Pearson相关系数法分析AP患者GLR、TyG指数与急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分的相关性;通过受试者工作特征(ROC)曲线分析GLR、TyG指数单独检测和联合检测对AP患者病情严重程度的预测价值。结果 高危组患者空腹血糖、三酰甘油、总胆固醇、C-反应蛋白(CRP)、降钙素原(PCT)、APACHEⅡ评分均高于低危组,淋巴细胞计数水平低于低危组(均P<0.05),两组患者在性别、年龄、体质量、BMI、吸烟、饮酒、高血压、胆系结石、白蛋白、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)等方面比较,差异均无统计学意义(均P>0.05);高危组患者GLR、TyG指数均高于低危组(均P<0.05);Pearson相关系数法分析结果提示,GLR、TyG指数与APACHEⅡ评分均呈正相关(均P<0.05);ROC曲线提示,GLR、TyG指数预测AP患者是否高危的敏感度分别为73.91%、72.52%,特异度分别为74.73%、75.52%,曲线下面积(AUC)分别为0.769、0.718,两项指标联合分析时敏感度为80.71%,特异度为75.13%,AUC为0.904,联合检测的预测价值更高(均P<0.05)。结论 高危组AP患者体内血糖、血脂水平高,炎症反应严重,GLR、TyG指数对于AP高危有一定预测价值,且两项指标联合的预测价值高于单一指标,可为临床中AP的诊治提供参考依据。

关键词： Single-cell RNA sequencing   Colorectal tumorigenesis   Tumor microenvironment   Traditional Chinese medicine   CCL22^(+)dendriticcells   CD4^(+)regulatory T cells   TMEM131   TNF signaling pathway  

摘要： Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma,accompanied by dynamic changes in the tumor microenvironment(TME).A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction(SBJDD)in preventing colorectal ***,the mechanism remains *** this study,we employed single-cell RNA sequencing(scRNA-seq)to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow *** RNA sequencing was utilized to assess the underlying *** results constructed the mutually verifiable single-cell transcriptomic atlases in Apc^(Min/+)mice and clinical *** was a marked accumulation of CCL22^(+)dendritic cells(DCs)and an enhanced immunosuppressive action,which SBJDD and berberine *** treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22^(+)DCs,which may represent“exhausted DCs”.Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic ***131 derived CCL22+DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal *** findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer(CRC),suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

关键词： 血脂异常   T细胞免疫   山楂提取物   过氧化物酶增殖活化受体γ   实验研究  

摘要： 目的:探讨山楂提取物通过调控高脂小鼠T细胞免疫及脂代谢防治血脂异常的作用机制研究。方法:60只健康雄性6周龄无特定病原体(SPF)级C57BL/6J小鼠适应性饲养1周后随机分为正常对照组、高脂饮食(HFD)组、HFD+高剂量山楂提取物组、HFD+中剂量山楂提取物组、HFD+低剂量山楂提取物组、HFD+阿托伐他汀组。正常对照组给予普通饲料正常饲养8周,HFD组小鼠给予60%脂肪供能高脂饲料喂养8周。HFD+高剂量山楂提取物组、HFD+中剂量山楂提取物组、HFD+低剂量山楂提取物组小鼠在高脂饲养4周后,分别灌胃5.2、2.6、1.3 g/kg山楂提取物,每日1次;HFD+阿托伐他汀组小鼠在高脂饲养4周后灌胃10 mg/kg阿托伐他汀,每日1次;对照组与HFD组同时间以等量生理盐水灌胃,干预周期为4周。蛋白免疫印迹法(Western Blot)及逆转录聚合酶链式反应(qRT-PCR)检测CD36和过氧化物酶增殖活化受体γ(PPARγ)的蛋白和mRNA表达水平;流式细胞术检测小鼠脾脏组织调节性T细胞(Treg)、抑制辅助性T细胞(Th17)、滤泡辅助性T细胞(Tfh)比例。结果:与正常对照组相比,HFD组小鼠体质量升高(P<0.01);CD36、PPARγmRNA及蛋白表达水平升高(P<0.01);脾脏Th17细胞比例升高,Treg、Tfh细胞比例降低(P<0.01)。与HFD组小鼠相比,经山楂提取物与阿托伐他汀干预的模型小鼠CD36、PPARγmRNA及蛋白表达水平降低(P<0.01),Treg、Tfh细胞比例升高(P<0.01),Th17细胞比例降低(P<0.01),HFD+高剂量山楂提取物组与HFD+阿托伐他汀组作用效果显著(P<0.05或P<0.01)。结论:山楂提取物能够改善高脂模型小鼠Treg、Th17、Tfh细胞失衡及CD36与PPARγ受体表达,山楂提取物调脂可能与T细胞免疫及脂代谢分化相关。

关键词： 多巴酚丁胺   沙库巴曲缬沙坦   慢性心力衰竭   疗效   心肌损伤  

摘要： 目的 探讨多巴酚丁胺与沙库巴曲缬沙坦联合治疗慢性心力衰竭（CHF）的效果及对白细胞介素-33（IL-33）/生长刺激表达基因2蛋白（ST2）通路分子的影响。方法 选取2021年1月至2023年7月于皖南医学院第二附属医院接受基础抗心力衰竭治疗的CHF患者108例为研究对象，按照随机数字表法分为对照组（沙库巴曲缬沙坦治疗）和试验组（多巴酚丁胺+沙库巴曲缬沙坦治疗），每组54例。比较两组治疗前后心功能、心肌损伤因子[N-末端脑钠肽前体（NT-proBNP）、心肌肌钙蛋白T（cTnT）、肌酸激酶同工酶（CK-MB）、血管紧张素Ⅱ（AngⅡ）]、外周血IL-33、ST2 mRNA和蛋白表达水平及不良反应情况；并比较随访半年再发心力衰竭和再次住院发生率。结果 试验组总有效率（94.44%）高于对照组（81.48%）（P＜0.05）；治疗3个月后试验组左心室舒张末期内径（LVEDD）、左室射血分数（LVEF）、左室收缩期内径（LVESD）改善幅度优于对照组（P＜0.05）；血清CK-MB、cTnT、NT-proBNP、AngⅡ水平及外周血IL-33、ST2 mRNA和蛋白表达水平均低于对照组（P＜0.05）；两组不良反应发生率比较，差异无统计学意义（P＞0.05）；试验组再发心力衰竭、再次住院发生率均低于对照组（P＜0.05）。结论 多巴酚丁胺联合沙库巴曲缬沙坦治疗CHF患者，可协同增强疗效，减轻心肌损伤，调控IL-33/ST2通路表达，改善心功能，降低复发率及再住院率，改善患者预后，且安全性良好。

关键词： 小儿重症病毒性脑炎   人免疫球蛋白   甲泼尼龙琥珀酸钠   炎性因子  

摘要： 目的探讨小儿重症病毒性脑炎在人免疫球蛋白给药基础上,联用甲泼尼龙琥珀酸钠静脉滴注效果及对IL-6、hs-CRP影响。方法对我院在2017年6月至2023年6月期间共计82例小儿重症病毒性脑炎抽取,严格执行随机原则做分组操作,各有41例计入,对照组运用人免疫球蛋白制剂加以治疗,观察组同时取甲泼尼龙琥珀酸钠联用。结果治疗后,观察组患儿总有效率居于更高水平(P<0.05);症状消失时间数据相较对照组呈更低显示(P<0.05)。炎性因子指标值低于对照组,免疫功能指标CD3^(+)、CD4^(+)高于对照组,CD8^(+)低于对照组,神经功能损伤指标值低于对照组(P<0.05);不良反应率未见差异(P>0.05)。结论按重症病毒性脑炎予以诊断的患儿在人免疫球蛋白给药基础上,联用甲泼尼龙琥珀酸钠静脉滴注可提高总有效率,降低炎性反应程度,增强免疫功能,促进神经功能恢复,且具一定安全性。

摘要： Tra queste, spicca l'importanza della prevenzione, che va però declinata con un approccio lungo tutto l'arco della vita - il cosiddetto life-course approach. È quindi fondamentale una comunicazione aperta e attiva tra le diverse realtà locali per portare avanti istanze comuni e determinare livelli standard di at tività epidemiologica a supporto del Ssn sia a livello territoriale e di comunità sia in ambito ospedaliero. Da questa prospettiva, la risposta è sì: se ne ha la possibilità, l'epidemiologo deve anche porsi l'obiet tivo di contribuire alla riduzione - se non all'eradi cazione - della povertà, attraverso l'evidenza scien tifica.

关键词： 乙型肝炎病毒   慢性乙型肝炎   核苷(酸)治疗   停药   细胞免疫  

摘要： 接受核苷(酸)类药物(NAs)治疗的慢性乙型肝炎(CHB)患者往往需要终生服药。临床上常有患者因擅自停药引发病毒学反弹、肝炎复发,甚至出现急性肝功能衰竭和死亡。一些临床研究显示,基于规则的安全停药可使部分患者实现血清乙型肝炎表面抗原(HBsAg)的清除,获得临床治愈。因此,能否通过按规则停用NAs治疗,实现部分优选人群的血清HBsAg清除,是目前临床面临的难题和热点问题。CHB患者宿主的抗病毒免疫通过清除感染病毒的肝细胞实现对病毒的控制,但不可避免地也造成了肝脏损伤。在CHB自然史中,病毒与宿主免疫系统的相互作用不仅推动疾病进展,也促进病毒不断被清除,直至完全抑制。这一过程中,宿主的抗HBV特异性细胞免疫发挥着重要的作用。本文将综述慢性乙型肝炎患者在NAs停药后的结局与其相关的病毒指标、炎症指标和宿主抗HBV特异性细胞免疫,以帮助安全停药及识别停药后HBsAg清除的患者。