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关键词： 清热润肠方   坐浴疗法   肛裂   创面愈合   炎症因子  

摘要： 目的：观察清热润肠方坐浴疗法对肛裂术后创面愈合和炎性因子IL-6、TNF-α水平的影响。方法：将300例肛裂患者分为研究组和对照组，每组150例。两组均采用肛裂切除术治疗，对照组采用1:5000高锰酸钾液坐浴，研究组采用清热润肠方坐浴。均给予常规换药，直到创面愈合。对比两组治疗效果，比较术后1d、7d创面疼痛、分泌物以及肉芽生长积分的情况，对比术后1d、7d的IL-6、TNF-α浓度水平，比较创面愈合时间和创面感染率情况。结果：研究组治疗后愈显率为91.33%，高于对照组78.00%（P＜0.05）；创面分泌物、疼痛以及肉芽生长积分方面，研究组术后7d相较于对照组更低（P＜0.05）；研究组术后7d血清炎性因子IL-6、TNF-α水平低于对照组（P＜0.05）；研究组创面愈合时间和感染率均低于对照组（P＜0.05）。结论：清热润肠方熏洗对肛裂术后创面愈合具有促进作用，可降低炎症反应和感染发生率，提高临床治疗疗效，值得推广应用。

关键词： 养血口服液   阿尔茨海默病   PI3K/Akt/TNF-α   认知功能障碍  

摘要： 目的：探究养血口服液改善AD小鼠认知功能的疗效及潜在作用机制。方法：将40只APP/PS1双转基因小鼠随机分为模型组（Model组）、养血口服液低剂量组（YX-D组）、养血口服液中剂量组（YX-Z组）、养血口服液高剂量组（YX-G组），10只同系背景非转基因C57BL/6小鼠为空白组（Control组）。连续灌胃14d后，Morris水迷宫检测认知功能，海马组织进行刚果红染色，WB、RT-qPCR法检测小鼠海马区PI3K/Akt/TNF-α通路上蛋白及mRNA表达量的变化情况。结果：与Model组相比，YX-G、YX-Z组小鼠游泳总路程及上平台潜伏期均减少，穿越平台次数增多，具有统计学差异（P<0.05）；YX-G组老年斑（SP）减少最为明显；YX-G组小鼠海马组织中PI3K、AKT mRNA表达水平升高，TNF-α基因表达水平降低，具有统计学差异（P<0.05）；YX-G组小鼠海马组织中PI3K、Akt蛋白表达水平无差异，p-PI3K蛋白表达水平升高，TNF-α蛋白表达水平降低，具有统计学差异（P<<0.05）。结论：养血口服液可以改善AD小鼠的认知功能，减少海马区SP沉积，其机制可能与调控PI3K/Akt/TNF-α信号通路有关，且有剂量依赖性趋势，高剂量组效果优于低中剂量组。

关键词： HLA   genes   multiple sclerosis  

摘要： Multiple sclerosis (MS) is a chronic autoimmune disease characterized by the immune system attacking the central nervous system, leading to demyelination and neurodegeneration. This work investigates the relationship between specific human leukocyte antigen (HLA) polymorphisms and MS, aiming to reveal the immunogenetic background of this disease for more individualized management approaches. This study employed a case-control design, analyzing HLA allele frequencies in 179 MS patients and 200 control subjects using next-generation sequencing, The key findings indicate significant associations between several HLA Class I and II alleles and MS, including HLA-B*35:03:01:03, HLA-C*04:01:01:14, HLA-DRB1*15:01:01:26, and HLA-DQA1*05:05:01:02. These findings emphasize the critical role of HLA molecules in MS Romanian patients.

关键词： high resolution   HLA alleles   HLA haplotypes   NGS  

摘要： HLA typing of 9126 haematopoietic stem cell donors living in the Asian and European parts of Russia and identifying themselves as Russians was performed using NGS technology in 2-field resolution at the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci. The study of donors in the Asian part of Russia disclosed 77 alleles at the HLA-A locus, 111 at the HLA-B locus, 58 at the HLA-C locus, 54 at the HLA-DRB1 locus, and 26 at the HLA-DQB1 locus. Donors of the European part of Russia are characterised by the following allelic diversity: 87 alleles at the HLA-A locus, 136 at the HLA-B locus, 72 at the HLA-C locus, 67 at the HLA-DRB1 locus, and 37 at the HLA-DQB1 locus. The most common five-locus haplotype in both populations is HLA-A*01:01 similar to HLA-C*07:01 similar to HLA-B*08:01 similar to HLA-DRB1*03:01 similar to HLA-DQB1*02:01. Throughout the study, 26 new alleles were revealed.

关键词： COX2   kaempferol   mesothelial-mesenchymal transition   network pharmacology   postoperative peritoneal adhesions  

摘要： Postoperative peritoneal adhesion (PA) formation is a common complication after abdominal surgery and can result in various severe outcomes. Inflammation and fibrosis are important processes in PA formation. The effectiveness of kaempferol (KF), a common component of several medications used to reduce inflammation and prevent fibrotic diseases, in preventing postoperative PA formation is unknown. This study explored the effectiveness and mechanism of KF in preventing PA formation following surgery. The animal adhesion model revealed that KF could effectively prevent adhesions formation and inhibit mesothelial-mesenchymal transition (MMT). Protein-protein interaction and pathway enrichment analyses revealed that TNF-alpha may be the key target through which KF prevents adhesion formation. Here, KF was found to inhibit TNF-alpha-induced MMT. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that common genes between KF and PA are enriched in the TNF signalling pathway. Moreover, cyclooxygenase 2 (COX2) was identified as a downstream target of TNF-alpha whose expression is positively correlated with adhesion formation. Most importantly, COX2 small interfering RNA (siRNA) and overexpression plasmid (OE) transfection experiments confirmed that KF inhibits MMT by blocking the TNF-alpha/COX2 signalling pathway. Finally, molecular docking revealed that TNF-alpha is a binding target of KF. In conclusion, these results suggest that KF inhibits MMT by blocking the TNF-alpha/COX2 signalling pathway, thus attenuating adhesion formation. These results provide new insights into the development of antiadhesion drugs.

关键词： topical IgY therapy   thermosensitive hydrogel   sustained-release delivery   skin anti-inflammation   cutaneous healing  

摘要： With the progression of biomedical therapies, antibodies have emerged as promising agents for treating inflammatory skin disorders due to their specificity and antigen-targeting capabilities. Antibodies play a crucial role in epidermal injury repair by precisely regulating inflammatory pathways and neutralizing key inflammatory factors. Notably, conventional IgG antibodies face limitations including poor stability, immunogenicity, and reduced efficacy in epidermal environments. Therefore, developing an alternative antibody delivery system capable of overcoming these limitations has become a critical issue to address. Egg yolk antibody (IgY), with its unique Fc structure, exhibits excellent thermal stability and biosafety, making it ideal for treating skin and mucosal diseases. Here, this study proposes an innovative topical IgY hydrogel sustained-release system (IgY-Gel) to deliver TNF alpha-specific IgY (anti-TNF alpha IgY), which is demonstrated to effectively reduce the levels of inflammatory factors like IL-6 in LPS-stimulated RAW264.7 cells. The system synergizes with thermosensitive chitosan/beta-glycerophosphate (CS/beta-GP) hydrogels exhibiting controlled-release properties to enhance the proliferation and migration of human umbilical vein endothelial cells (HUVECs) under pro-inflammatory conditions. In addition, this system demonstrates accelerated wound healing in a mouse wound model, with a significantly higher healing rate of 95.7% in the anti-TNF alpha IgY-Gel group after 14 days, compared to the respective rates of 73.7%, 77.6%, and 81.7% in control, blank-Gel, and ns IgY-Gel groups, respectively. In conclusion, our IgY-Gel system highlights the anti-inflammatory and wound-healing potential of topical IgY therapy. This innovative system promotes the translational application of antibody therapies toward engineered biologics with enhanced efficacy and safety profiles in tissue repair processes.

摘要： Inflammatory bowel diseases (IBD) affect millions of people worldwide. The use of anti-TNF-alpha for the treatment of moderate-to-severe IBD faces primary non-response, loss of response during treatment or intolerance issues. As an alternative, a strategy consisting of oral administration of TNF-alpha siRNA was evaluated in the present study for the local treatment of IBD. TNF-alpha siRNA entrapped in lipid nanoparticles (LNPs) was microencapsulated in gastroresistant alginate particles using an original process. The encapsulation yield of both siRNA and LNPs in microparticles (MPs) was at least 90%. Oral administration of MPs significantly reduced both clinical score and therapeutic index in a TNBS-induced colitis model in mice. Near complete removal of tissue damage, including edema, ulceration and necrosis, was observed in colon sections from treated mice. Reduced variation in gene sets involved in the global inflammatory response and the TNF-alpha/NF-kappa B signaling pathway was detected in the colon compared to untreated mice, demonstrating the anti-inflammatory activity of MPs. Finally, biodistribution studies showed the targeting of the inflamed colon by MPs and the colocalization of LNPs and MPs at the site of action. These MPs may represent a promising siRNA delivery platform for the oral treatment of IBD.

关键词： Mucosal immunology  

摘要： The airway epithelium plays a crucial role in maintaining lung homeostasis, and its dysregulation is often linked to various lung diseases, including asthma. Ciliated cells, abundantly present in the mammalian airway epithelium, have a critical function in clearing inhaled particles and pathogens. We show here that ciliated cells constitutively express IL-17D, which functions as an immune brake in limiting allergic inflammation in murine models of asthma. Mechanistically, IL-17D functions to prevent influx of classical monocytes into the lung and their subsequent conversion to pathogenic alveolar macrophages, through binding to CD93. Deficiency in Il17d or Cd93 increased the expression of chemokine receptors on classical monocytes, including CCR6, thereby enhancing their recruitment to the lung and type 2 inflammation. Our study thus reveals an unexpected protective role of ciliated cells and IL-17D in lung immune responses and asthma, which can be further explored for treating related diseases.

摘要： PURPOSE:The phase II NIVOREN GETUG-AFU-26 study assessed the safety and activity of nivolumab in a real-world population with pretreated advanced clear cell renal cell carcinoma (aRCC). A comprehensive translational research program was conducted including blood and tissue-based analyses. Herein we assessed circulating factors at baseline, their association with intratumoral immune contexture and outcomes. EXPERIMENTAL DESIGN:Baseline blood samples were prospectively collected from 353 patients included in the NIVOREN trial. A cohort of 80 patients including 40 responders and 40 with primary progressive disease, was used for biomarker discovery, with fourteen soluble factors (VEGF,VCAM-1, IL-6, IL-7, IL-8, IL-10,APRIL, BAFF, 4-1BB, BCA, SDF-1, MDC, IFN-gamma and TNF-alpha) assessed for association with overall survival (OS) (discovery set). Candidate biomarkers were subsequently assessed in the remaining 273 patients for association with outcomes (validation set). Gene expression signatures were assessed on baseline tissue samples using RNA sequencing. RESULTS:Five candidate biomarkers, IL-6,IL-7,IL-8,VEGF, and 4-1BB, were significantly associated with OS in the discovery set. We confirmed in the validation set a significant adverse association between OS and higher baseline levels of IL-6, IL-8, VEGF, with respective hazard ratios of 3.17 (95%CI 2.29-4.40), 2.11 (95%CI 1.60-2.80), and 1.36 (95%CI 1.04-1.79). Higher IL-6 and IL-8 levels were associated with an intratumor IMmotion myeloid gene expression signature (p=0.004 and p=0.041 respectively). CONCLUSIONS:Elevated baseline circulating IL-6/IL-8/VEGF are associated with worse outcomes in nivolumab-treated aRCC. Circulating IL-6 and IL-8 showed strongest association with outcomes and correlated with a myeloid tissue contexture, providing guidance for patient selection in future trials.