T6态ZL105-(Pr+Ce)合金的组织及力学性能研究

采用光学显微镜、扫描电子显微镜、EDS分析仪、布氏硬度与拉伸试验研究了混合稀土与T6热处理对ZL105合金的微观组织及力学性能的影响。结果表明,当添加0.5wt%的稀土(Pr+Ce)后,ZL105合金的α-Al相、共晶Si相及富Fe相均被细化。ZL105-0.5wt%(Pr+Ce)合金经T6热处理后,α-Al相进一步细化,晶粒趋于圆整,共晶Si相也进一步细化,由长条状转变为短颗粒状,但是富Fe相的形貌和尺寸没有发生明显变化。T6态ZL105-0.5wt%(Pr+Ce)合金的抗拉强度、伸长率及硬度分别为257.7 MPa、7.0%、98 HB。T6态ZL105-0.5wt%(Pr+Ce)合金的断口为典型的塑性断裂特征,断口表面出现了许多韧窝,主要以小韧窝为主,分布较均匀且密集。T6热处理后合金的力学性能得到了显著改善。

PRKCH的表达对CD8^(+)T细胞功能及黑色素瘤免疫治疗的影响

目的 探讨PRKCH表达对CD8^(+)T细胞功能的影响及其在黑色素瘤免疫治疗效果预测中的作用。方法 运用Kaplan-Meier法分析黑色素瘤免疫治疗队列以及肿瘤基因组图谱(TCGA)数据中PRKCH在黑色素瘤中的表达及其与总生存期(overall survival, OS)的相关性。利用单细胞RNA测序(single-cell RNA-sequencing, scRNA-seq)数据分析PRKCH的细胞表达群体,利用蛋白质互作网络(protein-protein interaction networks, PPI)和基因集富集分析(gene set enrichment analysis, GSEA)评估PRKCH诱导抗肿瘤免疫应答的机制。利用逆转录病毒过表达和敲减PRKCH,检测小鼠CD8^(+)T细胞功能。利用B16-OVA小鼠黑色素瘤模型验证PRKCH过表达的OT-1 CD8^(+)T细胞对肿瘤生长的影响。结果 在黑色素瘤免疫治疗队列和TCGA数据中,高水平的PRKCH显著延长患者OS(P<0.05)。scRNA-seq分析显示PRKCH可以在T细胞表达。PPI、GSEA和scRNA-seq分析显示PRKCH的高表达与更多的细胞毒性和记忆性T细胞形成相关。过表达和敲减PRKCH分别增强和减少CD8^(+)T细胞的增殖及IFN-γ、Granzyme B的表达。过表达PRKCH增强OT-1 CD8^(+)T细胞的肿瘤抑制能力。结论 PRKCH增强CD8^(+)T细胞抑制肿瘤进展的能力,并可以用于预测黑色素瘤免疫治疗效果。

T1期乳腺癌超声特征与ER、PR、HER-2、Ki-67表达的相关性分析

目的:探讨T1期乳腺癌超声声像图特征与雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体2(HER-2)、细胞增殖相关抗原Ki-67表达的相关性。方法:回顾性收集2012年1月至2021年6月经病理证实为单发乳腺恶性肿瘤患者493例的病历资料,记录超声特征及免疫组化结果,并对二者进行相关性分析。结果:ER、PR、HER-2、Ki-67阳性率分别为78.09%、67.34%、21.10%、71.60%;ER与PR表达呈正相关,HER-2与ER、PR表达呈负相关;Ki-67与HER-2表达呈正相关,与ER、PR表达呈负相关。ER阳性表达与形态不规则、边缘不规整、间质脂肪侵犯、有高回声晕等超声特征有关,PR阳性表达与病灶内部成分、腋窝淋巴结转移等超声特征有关,Ki-67阳性表达与边界不清晰、间质脂肪侵犯、有高回声晕等超声特征有关,差异均有统计学意义(P<0.05)。结论:T1期乳腺癌的超声征象与ER、PR、Ki-67表达存在一定的相关性,超声声像图的变化可以提示肿瘤生物学行为,为医生临床决策提供参考。

基于prompt tuning的中文文本多领域情感分析研究

不同领域的情感文本表达方式不一样,通常需要为各个领域训练相应的情感分析模型。针对无法用一个模型进行高效多领域情感分析的问题,提出了基于提示微调(prompt tuning)的多领域文本情感分析方法MSAPT。借助hard prompt,指示情感文本的所属领域和待选的情感标签,调动不同领域情感分析相关的知识,再为情感分析预训练一个统一的“通才模型”,在下游的各领域文本学习中,保持模型冻结,通过prompt tuning使模型学习到下游各领域情感文本的特征。MSAPT仅需保存一个模型和一些参数量远远小于模型的prompt,实现了多领域情感分析。在多个属于不同领域的情感文本数据集上进行实验,结果表明仅进行prompt tuning时,MSAPT效果优于模型微调(model tuning)的。最后,分别对适应特定领域的prompt tuning、hard prompt、soft prompt的长度和中间训练数据集的大小进行消融实验,从证明其对情感分析效果的影响。

Fine-tuning the activation behaviors of ternary modular cabazitaxel prodrugs for efficient and on-target oral anti-cancer therapy

The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of reducing substances (e.g., ascorbic acid, glutathione, uric acid and tea polyphenols) in the systemic circulation. This may lead to toxicity, particularly in oral prodrugs that require more frequent and high-dose treatments. Fine-tuning the activation kinetics of these prodrugs is a promising prospect for more efficient on-target cancer therapies. In this study, disulfide, steric disulfide, and ester bonds were used to bridge cabazitaxel (CTX) to an intestinal lymph vessel-directed triglyceride (TG) module. Then, synthetic prodrugs were efficiently incorporated into self-nanoemulsifying drug delivery system (corn oil and Maisine CC were used as the oil phase and Cremophor EL as the surfactant). All three prodrugs had excellent gastric stability and intestinal permeability. The oral bioavailability of the disulfide bond-based prodrugs (CTX-(C)S-(C)S-TG and CTX-S-S-TG) was 11.5- and 19.1-fold higher than that of the CTX solution, respectively, demonstrating good oral delivery efficiency. However, the excessive reduction sensitivity of the disulfide bond resulted in lower plasma stability and safety of CTX-S-S-TG than that of CTX-(C)S-(C)S-TG. Moreover, introducing steric hindrance into disulfide bonds could also modulate drug release and cytotoxicity, significantly improving the anti-tumor activity even compared to that of intravenous CTX solution at half dosage while minimizing off-target adverse effects. Our findings provide insights into the design and fine-tuning of different disulfide bond-based linkers, which may help identify oral prodrugs with more potent therapeutic efficacy and safety for cancer therapy.

基于PVsyst的光伏电站PR值优化设计

随着国外IPP项目的增加,IPP方对PR值的要求也更加苛刻,因此优化PR值是光伏电站设计的核心。基于PVsyst软件,分析支架、组件、电缆及变压器参数对PR值的影响,并结合项目成本,得出有利于项目的优化方案。基于实际项目,考虑PR值的影响因素、投资成本及PR值对应的性能罚则,对项目进行优化设计,最后得出可用于工程设计的指导原则。

Prevelance of Bovine Cysticercosis in Egypt and the Cysticidal Effect of Two Extracts Obtained from Balanites aegyptiaca and Moringa oleifera on Mice Model Affected with T. saginata Cysticerci

The aim of the present study was to determine the prevalence of bovine cysticercosis in both cattle and buffloas, in Egypt and to assess the cysticidal efficacy of Balanites aegyptiaca fruits (B. aegyptiaca) and Moringa oleifera seeds (M. oleifera) extracts in experimentally infected mice. The study detected the level of tumor necrosis factor (TNF-α) to monitor the immune and inflammatory responses of experimentally infected mice. Through meat inspection, a total number of 2125 male bovine, 2 to 5 years old, (1125 cattle and 1000 buffloes) were examined under the authority of Albsatine and Alwaraq official abattoirs in Cairo Governorate, Egypt covering the period extended from March 2022 to April 2023. The overall prevalence of the disease among bovine was 7.8% (6.31% of cattle and 9.5% of buffloes). Besides, B. aegyptiaca and M. oleifera extracts showed cysticidal activity in experimentally infected mice. A decrease in the numbers of cysticerci was found in all treated mice groups, and up to 88% reduction was achieved in the B. aegyptiaca-treated group;higher than that was recorded in both M. oleifera (72.23%) and albendazole-treated ones (80.56%). Postmortem findings proved that M. oleifera and B. aegyptiaca reduced cysticerci numbers comparable to a commercial anthelmintic. The study showed a significant decrease (P 0.001) in TNF-α levels after treatment with Balanites and Moringa extracts, compared with the untreated control and the albendazole-treated groups.

Pristane诱导的狼疮肾炎小鼠辅助性T淋巴细胞17变化的研究

目的:探讨Pristane诱导的狼疮肾炎小鼠体内辅助性T淋巴细胞17(T helper lymphocyte 17,Th17)数量及相关基因的改变。方法:在8周龄雌性Balb/c腹腔注射0.5mL pristane诱导构建狼疮小鼠模型,实验分为生理盐水组(SC)及pristane诱导组(PC)。在28周时测量小鼠踝关节直径、脾脏长度及质量,镜下观察肾脏病理,ELISA检测尿蛋白浓度、血清抗ds-DNA浓度,流式细胞术检测脾脏Th17,qPCR检测相关基因表达。结果:PC组踝关节直径(P<0.05)、脾脏质量(P<0.05)显著高于SC组,脾脏长度(P<0.05)显著长于SC组。PC组尿蛋白浓度(P<0.05)及血清抗ds-DNA抗体浓度(P<0.05)显著高于SC组。PC组Th17比例显著高于SC组(P<0.05)。PC组CCL19表达显著高于SC组(P<0.05)。结论:PC组小鼠Th17比例显著高于SC组。

Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

Milk fat globule membrane supplementation protects againstβ-lactoglobul-ininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner

Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

Scr、hs-cTnT、NT-proBNP与烧伤患者院内主要心血管不良事件的相关性分析

目的探讨血清肌酐(Scr)、高敏心肌肌钙蛋白T(hs-cTnT)、N末端B型利钠肽原(NT-proBNP)与烧伤患者院内主要心血管不良事件(MACE)的相关性及其预测价值。方法回顾性收集254例烧伤患者作为研究对象。根据住院期间是否发生MACE,分为MACE组(85例)和非MACE组(169例),比较2组临床基线资料和实验室指标水平,采用受试者操作特征(ROC)曲线评价Scr、hs-cTnT、NT-proBNP对烧伤患者院内并发MACE的预测价值。结果与非MACE组相比,MACE组患者年龄、烧伤总面积、Scr、hs-cTnT、NT-proBNP、胱抑素C水平更高(P均<0.05),同时2组性别、高血压病史、脓毒血症、吸烟史比较差异均有统计学意义(P均<0.05)。多因素分析显示,Scr、hs-cTnT、NT-proBNP是烧伤患者院内MACE的独立危险因素(P均<0.05)。ROC曲线分析显示,Scr、hs-cTnT、NT-proBNP及三者联合预测MACE的曲线下面积(AUC)值分别为0.743、0.802、0.733、0.801。DeLong检验显示,三者联合预测MACE的AUC值高于Scr单独预测(Z=2.897,P=0.003);Scr、hs-cTnT、NT-proBNP三者单独预测MACE两两比较差异均无统计学意义(Z值分别为1.398、0.202、1.900,P值分别为0.162、0.840、0.057)。亚组分析显示,hs-cTnT≥0.0145μg/L组烧伤患者MACE发生率高于hs-cTnT<0.0145μg/L组(P<0.05)。Spearman秩相关分析显示,hs-cTnT水平与烧伤严重程度呈正相关(P<0.05)。结论Scr、hs-cTnT、NT-proBNP是烧伤患者院内MACE的独立危险因素且具有良好的预测价值,hs-cTnT水平与烧伤患者严重程度相关。

S1PR2、ApoH、Let-7d在主动脉夹层中的表达及临床意义分析

目的分析S1PR2、ApoH、Let-7d在主动脉夹层中的表达及临床意义。方法选择2021年1月~2023年9月在南阳市中心医院利用胸腹主动脉CTA确诊主动脉夹层患者60例作为研究组,另选取同时期50例健康体检者作为对照组,以数字减影血管造影检查结果为金标准,将研究组患者按照病情严重程度分为轻度组(n=21)、中度组(n=19)、重度组(n=20)。比较2组人群S1PR2、ApoH、Let-7d表达、不同程度下各组人群S1PR2、ApoH、Let-7d表达、各种检测方式与三者联合检测检测对比、ROC曲线分析S1PR2、ApoH、Let-7d及三者联合诊断价值、S1PR2、ApoH、Let-7d水平与主动脉夹层疾病中的相关性。结果与对照组相比,研究组人群S1PR2、Let-7d表达较低、ApoH表达较高(P<0.05);重度组人群S1PR2、Let-7d表达均低于轻度、中度人群,重度组人群ApoH表达高于轻度、中度人群;本次研究中使用S1PR2阳性为5例、ApoH阳性为6例、Let-7d阳性为4例均低于联合检测阳性例数;三者联合AUC值(0.743)均高于S1PR2(0.552)、ApoH(0.343)、Let-7d(0.493);且三项联合灵敏度、特异度、准确度较高(P<0.05);以S1PR2、ApoH、Let-7d与主动脉夹层疾病中的相关性分析,S1PR2与主动脉夹层疾病的相关性呈现出负相关(r=-5.137,P=0.027)、ApoH与主动脉夹层疾病的相关性呈现出正相关(r=4.211,P=0.044)、Let-7d与主动脉夹层疾病的相关性呈现出负相关(r=-6.291,P=0.016)。结论S1PR2、ApoH、Let-7d在主动脉夹层疾病中的表达水平存在一定的相关性,将这三种指标结合起来,能够指导主动脉夹层疾病治疗及预后评估判断提供一定的理论基础。

Predicting the Prognosis and Immunotherapeutic Response of Triple-Negative Breast Cancer by Constructing a Prognostic Model Based on CD8+T Cell-Related Immune Genes

Objective Triple-negative breast cancer(TNBC)poses a significant challenge for treatment efficacy.CD8+T cells,which are pivotal immune cells,can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing technology.By leveraging these genes,our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to immunotherapy.Methods Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC databases.In the initial stage,we identified 67 differentially expressed genes associated with immune response in CD8+T cells.Subsequently,we narrowed our focus to three key genes,namely CXCL13,GBP2,and GZMB,which were used to construct a prognostic model.The accuracy of the model was assessed using the validation set data and receiver operating characteristic(ROC)curves.Furthermore,we employed various methods,including Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,immune infiltration,and correlation analyses with CD274(PD-L1)to explore the model's predictive efficacy in immunotherapeutic responses.Additionally,we investigated the potential underlying biological pathways that contribute to divergent treatment responses.Results We successfully developed a model capable of predicting the prognosis of patients with TNBC.The areas under the curve(AUC)values for the 1-,3-,and 5-year survival predictions were 0.618,0.652,and 0.826,respectively.Employing this risk model,we stratified the samples into high-and low-risk groups.Through KEGG enrichment analysis,we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism,whereas the low-risk group demonstrated significant enrichment in cytokine pathways.Furthermore,immune landscape analysis revealed noteworthy variations between(PD-L1)expression and risk scores,indicating that our model effectively predicted the response of patients to immune-based treatments.Conclusion Our study demonstrates the potential of CXCL13,GBP2,and GZMB as prognostic indicators of clinical outcomes and immunotherapy responses in patients with TNBC.These findings provide valuable insights and novel avenues for developing immunotherapeutic approaches targeting TNBC.

Double contrast-enhanced ultrasonography improves diagnostic accuracy of T staging compared with multi-detector computed tomography in gastric cancer patients

BACKGROUND Gastric cancer(GC)is the most common malignant tumor and ranks third for cancer-related deaths among the worldwide.The disease poses a serious public health problem in China,ranking fifth for incidence and third for mortality.Knowledge of the invasive depth of the tumor is vital to treatment decisions.AIM To evaluate the diagnostic performance of double contrast-enhanced ultrasonography(DCEUS)for preoperative T staging in patients with GC by comparing with multi-detector computed tomography(MDCT).METHODS This single prospective study enrolled patients with GC confirmed by preoperative gastroscopy from July 2021 to March 2023.Patients underwent DCEUS,including ultrasonography(US)and intravenous contrast-enhanced ultrasonography(CEUS),and MDCT examinations for the assessment of preoperative T staging.Features of GC were identified on DCEUS and criteria developed to evaluate T staging according to the 8th edition of AJCC cancer staging manual.The diagnostic performance of DCEUS was evaluated by comparing it with that of MDCT and surgical-pathological findings were considered as the gold standard.RESULTS A total of 229 patients with GC(80 T1,33 T2,59 T3 and 57 T4)were included.Overall accuracies were 86.9%for DCEUS and 61.1%for MDCT(P<0.001).DCEUS was superior to MDCT for T1(92.5%vs 70.0%,P<0.001),T2(72.7%vs 51.5%,P=0.041),T3(86.4%vs 45.8%,P<0.001)and T4(87.7%vs 70.2%,P=0.022)staging of GC.CONCLUSION DCEUS improved the diagnostic accuracy of preoperative T staging in patients with GC compared with MDCT,and constitutes a promising imaging modality for preoperative evaluation of GC to aid individualized treatment decision-making.

UBE2T mediates the stemness properties of breast cancer cells through the mTOR signaling pathway

Objectives:This study aimed to reveal the role and possible mechanism of the ubiquitin-conjugating enzyme 2T(UBE2T)in the biological activities of breast cancer stem cells(BCSCs).Methods:The specific protein and gene expression were quantified by Western blotting and quantitative real-time polymerase chain reaction,the proportion of BCSCs was examined by flow cytometry,and the self-renewal and proliferation of BCSCs were verified by serial sphere formation and soft agar.Results:Increasing expression of UBE2T was drastically found in breast cancer than that in adjacent tissues.Furthermore,UBE2T overexpression significantly increased the proportion of BCSCs in breast cancer cells and promoted their self-renewal and proliferation.Silent UBE2T exhibited the opposite functions.UBE2T increased the levels of the mammalian target of rapamycin and the phosphorylated mammalian target of rapamycin.Mammalian target of rapamycin(mTOR)inhibitor rapamycin inhibited the function of UBE2T in BCSCs.Conclusion:UBE2T plays a role in BCSCs through mTOR pathway and may suggest a novel therapeutic strategy for breast cancer.

T cell interactions with microglia in immune-inflammatory processes of ischemic stroke

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflammatory progression,mainly by secreting inflammatory factors.In the future,a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells,along with the activation of M2-type microglia.These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.

T2-weighted imaging-based radiomic-clinical machine learning model for predicting the differentiation of colorectal adenocarcinoma

BACKGROUND The study on predicting the differentiation grade of colorectal cancer(CRC)based on magnetic resonance imaging(MRI)has not been reported yet.Developing a non-invasive model to predict the differentiation grade of CRC is of great value.AIM To develop and validate machine learning-based models for predicting the differ-entiation grade of CRC based on T2-weighted images(T2WI).METHODS We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023.Patients were randomly assigned to a training cohort(n=220)or a validation cohort(n=95)at a 7:3 ratio.Lesions were delineated layer by layer on high-resolution T2WI.Least absolute shrinkage and selection operator regression was applied to screen for radiomic features.Radiomics and clinical models were constructed using the multilayer perceptron(MLP)algorithm.These radiomic features and clinically relevant variables(selected based on a significance level of P<0.05 in the training set)were used to construct radiomics-clinical models.The performance of the three models(clinical,radiomic,and radiomic-clinical model)were evaluated using the area under the curve(AUC),calibration curve and decision curve analysis(DCA).RESULTS After feature selection,eight radiomic features were retained from the initial 1781 features to construct the radiomic model.Eight different classifiers,including logistic regression,support vector machine,k-nearest neighbours,random forest,extreme trees,extreme gradient boosting,light gradient boosting machine,and MLP,were used to construct the model,with MLP demonstrating the best diagnostic performance.The AUC of the radiomic-clinical model was 0.862(95%CI:0.796-0.927)in the training cohort and 0.761(95%CI:0.635-0.887)in the validation cohort.The AUC for the radiomic model was 0.796(95%CI:0.723-0.869)in the training cohort and 0.735(95%CI:0.604-0.866)in the validation cohort.The clinical model achieved an AUC of 0.751(95%CI:0.661-0.842)in the training cohort and 0.676(95%CI:0.525-0.827)in the validation cohort.All three models demonstrated good accuracy.In the training cohort,the AUC of the radiomic-clinical model was significantly greater than that of the clinical model(P=0.005)and the radiomic model(P=0.016).DCA confirmed the clinical practicality of incorporating radiomic features into the diagnostic process.CONCLUSION In this study,we successfully developed and validated a T2WI-based machine learning model as an auxiliary tool for the preoperative differentiation between well/moderately and poorly differentiated CRC.This novel approach may assist clinicians in personalizing treatment strategies for patients and improving treatment efficacy.

Preventive effects of Bifidobacterium lactis Probio-M8 on ovalbumin-induced food allergy in mice

Food allergy is a significant public health concern globally.Certain probiotics have been found to enhance food allergy by regulating immune-microbe interactions in animal models and patients.However,the effects of Bifidobacterium lactis Probio-M8 on food allergy have not been thoroughly investigated.The present study examined the anti-allergic properties of Probio-M8,particularly in relation to immune response and gut microbiota composition.Results demonstrate that oral administration of Probio-M8 effectively mitigated the allergy symptoms triggered by ovalbumin(OVA)by ameliorating the morphological damage in the jejunum,reducing OVA-specific IgE and histamine levels in the serum,and suppressing Th2 cytokines(interleukin(IL)4 and IL-13)while increasing Th1 cytokines(interferon(IFN)γ)and regulatory T(Treg)cytokines(IL-10 and transforming growth factor(TGF)β1)in the culture supernatants of splenic cells.Furthermore,Probio-M8 effectively altered the diversity and composition of gut microbiota,particularly the relative abundances of Akkermansia_muciniphila in OVA-induced mice.Compared to the OVA group,the Probio-M8 group showed a decrease in the relative abundance of Akkermansia_muciniphila.In conclusion,Probio-M8 demonstrates the potential to alleviate food allergy by regulating the Th1/Th2 response and modulating gut microbiota,thereby offering a novel therapeutic strategy for patients with food allergy.

Identification of prognostic molecular subtypes and model based on CD8+ T cells for lung adenocarcinoma

Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.

Correlative factors of poor prognosis and abnormal cellular immune function in patients with Alzheimer’s disease

BACKGROUND Alzheimer’s disease(AD)is a serious disease causing human dementia and social problems.The quality of life and prognosis of AD patients have attracted much attention.The role of chronic immune inflammation in the pathogenesis of AD is becoming more and more important.AIM To study the relationship among cognitive dysfunction,abnormal cellular immune function,neuroimaging results and poor prognostic factors in patients.METHODS A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November 2020.Collect cognitive dysfunction performance characteristics,laboratory test data and neuroimaging data from medical records within 24 h of admission,including Mini Mental State Examination Scale score,drawing clock test,blood T lymphocyte subsets,and neutrophils and lymphocyte ratio(NLR),disturbance of consciousness,extrapyramidal symptoms,electroencephalogram(EEG)and head nucleus magnetic spectroscopy(MRS)and other data.Multivariate logistic regression analysis was used to determine independent prog-nostic factors.the modified Rankin scale(mRS)was used to determine whether the prognosis was good.The correlation between drug treatment and prognostic mRS score was tested by the rank sum test.RESULTS Univariate analysis showed that abnormal cellular immune function,extrapyramidal symptoms,obvious disturbance of consciousness,abnormal EEG,increased NLR,abnormal MRS,and complicated pneumonia were related to the poor prognosis of AD patients.Multivariate logistic regression analysis showed that the decrease in the proportion of T lym-phocytes in the blood after abnormal cellular immune function(odd ratio:2.078,95%confidence interval:1.156-3.986,P<0.05)was an independent risk factor for predicting the poor prognosis of AD.The number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score(r=0.578,P<0.05).CONCLUSION The decrease in the proportion of T lymphocytes may have predictive value for the poor prognosis of AD.It is recommended that the proportion of T lymphocytes<55%is used as the cut-off threshold for predicting the poor prog-nosis of AD.The early and continuous drug treatment is associated with a good prognosis.