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关键词： Influenza A virus   Fufang Shuanghua oral liquid   Antiviral immunity   Type I interferon   NLRP3-Inflammasome  

摘要： Ethnopharmacological relevance: As a traditional Chinese medicine (TCM)-originated antiviral prescription, Fufang Shuanghua oral liquid (FS) is extensively used for influenza virus therapy with a satisfying therapeutic efficacy in clinic. Aim of the study: The bioactive compounds (BACs) and the molecular mechanisms of FS against influenza A virus (IAV)-infected acute lung injury were investigated. Materials and methods: IAV-infected acute lung injury mouse model was established infected by IAV (H1N1) strain A/PR/8/34 to evaluate the pharmacological effects of FS. After both in vivo and in vitro chemical profiling using UHPLC-Q-Exactive-Orbitrap-MS/MS system, the clinical transcriptomic-based biomolecular network was analyzed to assess the key underlying mechanism of IAV infection. A series of in vivo experimental validations was carried out. Finally, an integrative research combining mapping network analysis, computational modeling and ADME models in silico was used for candidate BAC identification. Results: Oral administration of FS exhibited prominent improvement in IAV-induced acute lung injury mice, such as reducing the lung viral load, slowing the rate of weight reduction, and ameliorating pathological alterations. After the therapeutic effects validation, a total of 106 chemical compounds were characterized, and subsequently 21 absorbed components in the mice sera samples were identified after intragastric administration of FS using the UHPLC-Q-Exactive-Orbitrap-MS/MS system, including 12 prototype compounds and 9 metabolites. Clinical transcriptomic-based networks indicated that TNF-mediated antiviral immune response may be key mechanism of IAV infection. A series of in vivo validations revealed that FS treatment effectively restored antiviral immunity by regulating the protein expression levels of TNF mediated IFN signaling pathway and NLRP3 inflammatory signaling pathway, thereby downregulating the inflammatory factors/mediators, such as TNF-alpha, CXCL1, I

关键词： 眼部疾病   唾液酸结合免疫球蛋白样凝集素(Siglecs)   免疫调控   综述  

摘要： 近年来，眼部疾病中的免疫调控机制日益受到关注，逐步改写了眼球作为“免疫豁免”器官的传统认知。唾液酸结合免疫球蛋白样凝集素（Siglecs）是一类表达于免疫细胞的糖链识别受体，广泛介入免疫细胞的识别、活化与炎症调节。本文综述了Siglec家族在过敏性、自身免疫性及退行性眼部疾病中的表达特征与功能机制，评估了其作为生物标志物与干预靶点的临床潜力，有望深化对眼部疾病免疫病理的理解，拓展精准干预的新策略。

关键词： 克罗恩病   乌司奴单克隆抗体   围手术期   术后并发症   术后复发  

摘要： 克罗恩病（CD）在国内的发病率和患病率呈上升趋势，治疗药物也快速迭代更新。乌司奴单克隆抗体（UST）是一种抗白细胞介素12/23的新型生物制剂，为传统药物治疗或抗肿瘤坏死因子α制剂治疗失败的CD患者提供新选择。随着国内外相继批准UST用于成人CD的治疗，围手术期使用UST的CD患者也随之增加。本文基于CD患者围手术期应用UST的国内外最新研究证据进行综述，重点关注术前使用UST对术后近期和远期并发症的影响，以及术后使用UST对控制疾病活动的有效性。

关键词： Insulin resistance (Diabetes mellitus type 2)   Vitamin D   IL-6   TNF-alpha   Inflammatory markers  

摘要： Background Chronic low-grade inflammation is often seen in individuals with insulin resistance, characterised by increased levels of pro-inflammatory cytokines, such as TNF-alpha (tumour necrosis factor-alpha) and IL-6 (interleukin-6). Insulin resistance (IR) and vitamin D deficiency are increasingly recognised as interconnected metabolic issues. Research indicated that low vitamin D levels may impair insulin sensitivity, while insulin resistance can worsen vitamin D deficiency, creating a vicious cycle. This study aims to explore the relationship between TNF-alpha and IL-6 expression levels and vitamin D levels in insulin-resistant patients with type 2 diabetes mellitus (DM), and compare them with non-diabetic controls to better understand the role of vitamin D in inflammation, disease development, and progression. Methods From a total of 150 participants, 30 were healthy individuals (the control group), and 120 were patients with type II diabetes. The current case-control study compared TNF-alpha, IL-6 expression levels, and serum vitamin D levels between insulin-resistant patients and non-diabetic controls. Results The demographic and clinical variables were statistically significant. The case-to-control ratio was 4:1. Higher levels of TNF-alpha and IL-6 were found in DM patients compared to non-diabetic controls. Insulin-resistant patients exhibited higher IL-6 levels (5.47 +/- 0.30 pg/ml) than healthy participants (2.64 +/- 0.83 pg/ml), with p-value < 0.001. Vitamin D levels were significantly lower in DM patients (22.33 +/- 11.43 ng/ml) compared to healthy subjects (34.12 +/- 2.08 ng/ml), with p-value < 0.001. TNF-alpha levels were also significantly higher in DM patients (7.99 +/- 0.35 pg/ml) (p-value < 0.001) than in the healthy group (4.24 +/- 0.27 pg/ml). Using qPCR and measuring disease severity, the relationship between cytokine gene expression and insulin resistance was assessed. The positive associations between TNF-alpha, IL-6, vitamin D deficiency, p

关键词： fibrosis   IL-33/ST2 pathway   innate lymphoid cell   kidney disease   M2 macrophage  

摘要： Group 2 innate lymphoid cells (ILC2s) are tissue-resident immune cells that respond rapidly to epithelial-derived cytokines such as interleukin (IL)-33, producing type 2 cytokines including IL-5 and IL-13. Although ILC2s are well recognized for their roles in regulating inflammation and tissue remodeling in barrier organs, their functions in the kidney have only recently gained attention. In this review, we summarize the localization, activation, and effector functions of ILC2s in the kidney and explore their immunoregulatory interactions with macrophages, particularly in promoting M2 polarization. We further provide an overview of the therapeutic relevance of the IL-33/ST2/ILC2 axis in renal pathology, organizing current findings across models of acute kidney injury (AKI), chronic kidney disease (CKD), and glomerulonephritis (GN). ILC2s are primarily distributed in the perivascular tubulointerstitial regions of both the renal cortex and outer medulla, where they exert anti-inflammatory and antifibrotic effects through cytokine-mediated mechanisms. Importantly, recent studies suggest that the outcomes of IL-33-mediated interventions are highly context-dependent, influenced by factors such as dosage, disease phase, and temporal dynamics. A comprehensive understanding of the IL-33/ST2/ILC2 axis may offer new insights into immune modulation and tissue protection strategies for kidney diseases.

关键词： 癌,肝细胞   肝细胞癌   预后   免疫逃逸   程序性细胞死亡配体1   T细胞免疫球蛋白黏蛋白3  

摘要： 背景 肝细胞癌是全球第六大常见癌症，我国每年新增肝细胞癌病例数约为415 000例，占全球肝癌新病例总数的近一半。肝细胞癌可以通过多种免疫抑制性因子触发免疫逃逸，最终导致肿瘤的进展和转移。程序性细胞死亡配体1（PD-L1）和T细胞免疫球蛋白黏蛋白3（TIM3）作为近年来被发现的两种表达于肝细胞癌的免疫抑制性因子，其与肝癌患者的预后的关系目前尚不明确。目的 采用回顾性队列研究的方式，分析肝细胞癌PD-L1和TIM3表达水平对患者预后的影响。方法 本研究采用回顾性队列研究方法，分析2015—2018年河北医科大学第四医院肝胆外科行肝细胞癌根治性切除的82例患者的临床病理资料。采用多色荧光免疫组织化学染色的方式，检测患者石蜡切片中PD-L1阳性肿瘤细胞及TIM3阳性肿瘤细胞的数量及占总体肿瘤细胞的比例，采用Survival ROC法确定变量截断值，根据其表达水平将患者分组。依据PD-L1表达量将患者分为PD-L1+（n=21）及PD-L1-（n=61）两组，依据TIM3表达量将患者分为TIM3+（n=39）及TIM3-（n=43）两组，依据PD-L1及TIM3两者表达量将患者分为PDL1+/TIM3+（n=17）、PD-L1+/TIM3-（n=4）、PD-L1-/TIM3+（n=23）以及PD-L1-/TIM3-（n=38）四组。采用KaplanMeier法结合log-rank检验分析各组患者之间总体生存时间的差异。结果 通过Kaplan-Meier法结合log-rank检验分析，PD-L1+组（n=21）与PD-L1-组（n=61）的患者中位生存期（OS）比较，无统计学意义（中位OS=23.3个月vs52个月，P=0.051）,TIM3+组（n=39）与TIM3-组（n=43）的患者中位OS比较，无统计学意义（中位OS=27.6个月vs 52.9个月，P=0.210）,PD-L1+/TIM3+组（n=17）与PD-L1-/TIM3-组（n=38）的患者中位OS比较，无统计学意义（中位OS=18.5个月vs 53.4个月，P=0.030）。结论 PD-L1及TIM3单一因素的表达差异不足以影响肝细胞癌患者的预后，然而PD-L1及TIM3均呈高表达的患者的总体生存显著低于PD-L1及TIM3均呈低表达的患者。这说明PD-L1及TIM3可能在肝癌免疫逃逸的过程中起到协同作用。

关键词： ulcerative colitis   Mayo endoscopic score   endoscopic improvement  

摘要： Background: Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa, extending proximally from the rectum. However, the segmental pattern of healing in UC remains unclear. Endoscopic improvement (EI), a key therapeutic endpoint, is typically assessed using the Mayo endoscopic score (MES), which scores the worst affected area and may miss partial/segmental healing. This study evaluates healing patterns in UC and compares conventional MES with a 3-segment MES approach for detecting treatment effects in clinical trials. Methods: A post hoc analysis of HIBISCUS I/II and GARDENIA trials was conducted in UC patients with moderate-to-severe disease (MES >2 up to the descending colon). The primary outcome was the proportion of anti-tumor necrosis factor-treated participants achieving MES <= 1 in the descending colon, sigmoid colon, and rectum at week 10. Secondary outcomes included conventionally measured EI, segmental MES improvements, clinical response, and Patient-Reported Outcome 2 (PRO2) normalization. Outcomes were compared between adalimumab, infliximab, and placebo groups. Results: Among 300 participants, 217 received infliximab or adalimumab, while 83 received placebo. Healing followed a proximal-to-distal pattern, with the highest EI in the descending colon and the lowest in the rectum. Infliximab-treated patients continued this trend at week 54. Anti-tumor necrosis factor therapy significantly improved EI vs placebo (42.9% vs 19.3%;P < .001). No segmental MES approach outperformed conventional MES for detecting treatment effects. Combined endpoints (MES <= 1 + PRO2 normalization) better captured therapeutic benefits than PRO2 alone (28.6% vs 13.3%;P = .006). Conclusions: UC healing follows a proximal-to-distal pattern. Conventional MES remains superior for detecting treatment effects over segmental MES. Further studies should explore alternative endoscopic scoring methodologies.

关键词： DNA barcoding   Freshwater ecosystems   Invasive non-native species   Microsporidia   italic>Neocaridina davidi   Parasite transmission  

摘要： The introduction of non-native pet-traded species poses potential threats to global biodiversity, particularly in freshwater ecosystems. This study investigated the seasonal dynamics of microsporidian infections in an established feral population of cherry shrimp (Neocaridina davidi) and the coexisting populations of crustaceans, comprising both native and non-native species, inhabiting the thermal waters of the Fontcaude Park and the nearby Mosson River in southern France. Our aim was to assess the potential occurrence of spillover and/or spillback events between N. davidi and co-occurring crustaceans, as well as the influence of seasonal dynamics on these interactions. The prevalence and diversity of microsporidian parasites exhibited strong seasonal variations. Although parasites associated with the pet trade were not detected, we highlight the acquisition of native parasites by feral N. davidi, which seems to be a suitable alternative host for native host-generalist microsporidians. Our findings indicate that all prerogatives for spillback events to occur are met. Feral N. davidi may establish and survive year-round in European rivers with natural thermal regimes. Thus, human-mediated introductions can potentially alter parasite transmission dynamics in these ecosystems. L'introduction d'esp & egrave;ces non indig & egrave;nes, commercialis & eacute;es comme animaux de compagnie, constitue une menace potentielle pour la biodiversit & eacute;mondiale, en particulier dans les & eacute;cosyst & egrave;mes d'eau douce. Cette & eacute;tude examine la dynamique saisonni & egrave;re des infections microsporidiennes au sein d'une population f & eacute;rale & eacute;tablie de crevettes de David (Neocaridina davidi) et des populations coexistantes de crustac & eacute;s, indig & egrave;nes et non indig & egrave;nes, vivant dans les eaux thermales du parc de Fontcaude et de la Mosson, dans le sud de la France. Notre objectif & eacute;tait d'& eacute;valuer la survenue poten

关键词： 晚期结直肠癌   淋巴细胞亚群   细胞因子   免疫治疗   预测价值  

摘要： 目的 评估淋巴细胞亚群及细胞因子在预测晚期结直肠癌患者免疫治疗效果中的作用,以期为晚期结直肠癌患者的个体化治疗提供有效的临床预测工具。方法 收集江苏省苏州市立医院2022年10月至2025年4月收治的接受程序性细胞死亡受体1/程序性细胞死亡受体配体1抑制剂治疗的52例晚期结直肠癌患者的临床资料进行回顾性分析。根据实体瘤疗效评价标准分为完全缓解、部分缓解、疾病稳定和疾病进展,其中完全缓解、部分缓解、疾病稳定患者归入控制组（29例）,疾病进展归入进展组（23例）。比较2组治疗前后淋巴细胞亚群(调节性T细胞、CD3+、CD4+、CD8+、CD19+、自然杀伤细胞)和细胞因子[白细胞介素2（IL-2）、IL-4、IL-6、IL-10、肿瘤坏死因子α、γ干扰素]的水平,分析其与免疫治疗效果的相关性。结果 治疗前控制组自然杀伤细胞水平显著高于进展组[19.1 （14.6,24.9）%比8.0 （7.2,18.2）%]（P=0.041）。治疗后进展组IL-6显著高于治疗前,控制组显著低于治疗前,控制组低于进展组[4.7 （3.5,9.5）ng/L比17.3（14.7,47.4） ng/L],差异有统计学意义（均P <0.05）。通过Pearson相关性分析发现,IL-6与肿瘤进展呈负相关关系（r=-0.489,P=0.003）,提示IL-6水平越高,治疗效果越差。结论 自然杀伤细胞和IL-6在预测晚期结直肠癌患者免疫治疗效果中具有潜在价值。自然杀伤细胞水平的升高与更好的治疗反应相关,而IL-6的升高则可能预示较差的预后。