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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。

关键词： Malaria   Immune responses   Uric acid   Cytokines   River nile state  

摘要： Background Malaria, a prevalent disease in Sudan, has a significant impact on socioeconomic conditions. Cytokines play a crucial role in regulating the immune response during infectious diseases. This study investigates the interplay between malaria and immune response modulation in the River Nile State, focusing on tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta1 (TGF-beta 1), and interleukin-10 (IL-10). Method Ninety participants with microscopy-confirmed malaria were enrolled. Parasite density and COVID-19 co-infection were assessed. Cytokine levels were measured using ELISA. Results TNF-alpha, IFN-gamma, and TGF-beta 1 levels were significantly associated with parasite density (P < 0.05), but not IL-10. TGF-beta 1 was significantly higher in P. vivax infections, while IL-10 was elevated in P. falciparum cases. Uric acid levels were lower in participants co-infected with COVID-19 (P < 0.05). Conclusion The study's findings show how cytokines affect the immune response, impacting both parasite clearance. TNF-alpha, IFN-gamma, and TGF-beta 1 are positively linked to parasite density (r = 0.42, 0.38, 0.51;P < 0.01). IL-10 levels were higher in P. falciparum compared to P. vivax (560.0 vs. 415.6 pg/mL, P = 0.019).

关键词： Alcohol   Acute duodenal injury   Ethnopharmacology   Ampelopsis grossedentata   Apoptosis   TNF-a  

摘要： Ethnopharmacological relevance: Ampelopsis grossedentata (AG) is a popular folk tea that has been used in China for more than 1000 years. It is noteworthy that AG is widely recognized for preventing alcohol hangover in folk, and its protective effects on alcohol-induced hepatic steatosis have been demonstrated. Aim of the study: Alcohol overconsumption can induce acute duodenal injury (ADI) that lacks effective therapeutic strategies. This study investigated the gastrointestinal protective effects of AG on alcoholic ADI in mice. Materials and methods: AG extract was chemically characterized by HPLC analysis. Institute of Cancer Research (ICR) mice were pre-administered AG extract via gavage, and then subjected to an ethanol-induced ADI. After treatment, duodenal tissues were stained with hematoxylin and eosin (H&E), and cell apoptosis was detected by TUNEL staining and immunofluorescence. Untargeted metabolomics was employed to identify the differentially expressed metabolites, and the gene expressions of duodenal tissues were determined using RNA sequencing, immunofluorescence, immunohistochemistry, and western blotting. Results: Acute ethanol administration caused severe duodenal damage, characterized by necrosis and shedding of duodenal villi, hemorrhagic injury, mucosal edema, and disruption of intestinal barrier in mice, which was improved by the pre-treatment with AG extract. Notably, administration of AG aqueous extract suppressed ethanol-induced duodenal villous apoptosis in mice by inhibiting caspase-3/7. In addition, untargeted metabolomics data showed AG extract improved ethanol-induced disruption of amino acid biosynthesis and metabolism, and increased the levels of amino acids, such as L-serine, L-histidine, L-leucine, L-glutamine and Ltryptophan. RNA sequencing analysis revealed that ethanol intake activated TNF, IL-17, MAPK and apoptosis pathways, and these pathways were inhibited by AG extract pre-treatment. Immunofluorescence and immunohistochemistr

关键词： Major histocompatibility complex   Sequence alignment   Multiple alignment calculation   Contaminants   Protein sequencing   B cells   Database searching   Vaccines  

摘要： Background The goal in vaccinology is to identify candidate antigens for clinical trials that will elicit an immune response for a significant portion of the target population. Unfortunately, promising data generated at the preclinical level often cannot be replicated in larger sample sizes. The goal of this project was to develop a methodology for processing MAE-generated data to identify MHC epitopes, minimize non-specific contaminants, find binding motifs, and utilize genetic connections among donors to determine which peptides were presented by specific MHC *** Our approach demonstrated that mild acid elution of peptides from seven consanguineous B-lymphocyte lines accurately reflects the HLA genotypes within family members, highlighting the specificity of MAE. Additionally, the data successfully reproduced known MHC binding motifs and partially deconvoluted the originating HLA alleles of the *** These findings suggest that our approach could be applied to numerous cell lines globally to evaluate a wide array of HLA haplotypes. This may help to reveal candidate vaccine antigens that induce immune protection for a wider population.

关键词： atopic dermatitis   caspase-1   CD81   IL-18   pathogenic group 2 innate lymphoid cells   single-cell RNA sequencing  

摘要： Autonomous artificial intelligence (AI) models for deciding treatment strategies are available but rarely applied prospectively in clinical settings. Here we present a prospective study of deploying daGOAT, an algorithm we have developed, as a conditional autonomous AI agent to prescribe a drug to prevent severe (grade 3-4) acute graft-versus-host disease (acute GvHD) following human leukocyte antigen (HLA)-mismatched haematopoietic cell transplantation (***, NCT05600855). During the enrollment period physicians invite 85% of eligible patients to participate and 88% of the invited patients agree. Among the 110 enrolled participants who receive HLA-haploidentical transplants, daGOAT predicts intermediate to high risk of severe acute GvHD in 57 participants between days +17 and +23 posttransplant and prescribes ruxolitinib in addition to the existing regimen to intensify immune suppression. The initial compliance with AI prescription is 98% (56/57), with dose and/or schedule deviating from the AI prescription within one month in a total of eight participants. In conclusion, we show that many physicians and patients are receptive to using conditional autonomous AI to prescribe a drug and that the decision for pharmaceutical intervention could be facilitated by autonomous AI.