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关键词： diagnostic algorithm   immune checkpoint inhibitor therapy   melanoma   sarcoidal reactions   soluble IL-2-receptor  

摘要： Background and Objectives Drug-induced sarcoidosis-like reaction (DISR) is an adverse event with emerging importance during immune checkpoint inhibitor (ICI) treatment in melanoma patients. Its reported frequency varies widely, making accurate diagnosis crucial. Distinguishing DISR from tumor progression is challenging, and misdiagnosis may lead to detrimental treatment changes. Thus, reliable diagnostic markers complementing histopathology as well as a diagnostic algorithm are *** and methods This single-center retrospective study, conducted at the University Medical Center in Leipzig, Germany, from 09/2019 to 06/2021, assessed DISR prevalence in melanoma patients treated with ICI for metastatic melanoma. We examined clinical characteristics, radiology, histopathology, and serum *** From a total of 177 patients 19 patients were suspicious for DISR. Of those, DISR was diagnosed in seven patients. In a further nine patients DISR was highly probable based on radiological findings and noticeably increased soluble interleukin-2-receptor (sIL2R) levels, resulting in DISR prevalence of 9%. No patient required permanent discontinuation of ICI due to *** In melanoma patients receiving ICI, DISR is common. Histological confirmation through mediastinoscopy or pulmonary wedge resection offers the highest diagnostic accuracy. When histology is not available, sIL2R levels can aid diagnosis. We propose an algorithm to distinguish DISR from tumor progression.

关键词： Hypertensive nephropathy   Rehmannioside A   Inflammation   Fibrosis  

摘要： Background: This study aimed to observe the influences and potential mechanism of rehmannioside A (ReA) in hypertensive nephropathy (HN). Methods: HN model in mice and rat tubular epithelial cells were constructed by angiotensin II (Ang II). The biomarkers of renal function, including uric acid (UA), creatinine (Cre), blood urea nitrogen (BUN), and urine albumin, were assessed. Results: Ang II induced severe kidney injury, while the injury was ameliorated by ReA. In Ang II-induced hypertensive mice model, ReA decreased the levels of UA, Cre, BUN, urine albumin, transforming growth factor (TGF)-beta, Fibronectin, Collagen I, interleukin (IL)-6, IL-1 beta, and tumour necrosis factor (TNF)-alpha. In Ang II-treated cells, ReA reduced the levels of TGF-beta, Fibronectin, Col1agen I, IL-6, IL-1 beta, and TNF-alpha. In vivo and in vitro, ReA promoted angiotensin converting enzyme 2 (ACE2) expression and inhibited the expression of angiotensin II type 1 receptor (AT1R), ACE, IL-17, mitogen activated protein kinase 14 (MAPK14), phosphorylated (p)-MAPK14, p-NF-kappa B P65, and matrix metallopeptidase 9 (MMP-9) in HN model. Moreover, there was a docking for ReA and MAPK14 protein, and ReA inhibited MAPK14 protein expression by promoting MAPK14 ubiquitination. Under Ang II treatment, MAPK14 overexpression reversed the promotive effect of ReA on cell viability and the inhibitory effects of ReA on fibrosis and inflammation in NRK-52E cells. Conclusions: ReA alleviated renal dysfunction and reduced fibrosis and inflammation, which was related to the inhibition of AT1R/MAPK14/IL-17 pathway. For HN treatment, ReA may be a promising pharmacological strategy.

关键词： DHA   Anti-PD-1   Angiogenesis   Tumor immune   Breast cancer   TNF-alpha  

摘要： Tumor vascular abnormality promotes the formation of immunosuppressive microenvironment, thus limiting the efficacy of tumor immunotherapy and promoting tumor development. Dihydroartemisinin (DHA) has shown potential as an anti-tumor agent. The potential role of its anti-angiogenic effect has not yet been discovered. This research investigates whether DHA inhibits tumor-induced angiogenesis, promotes immunotherapy and explored the underlying mechanism. The promoting effect of 4T-1 cell-conditioned media (CM) on SVEC4-10 activity and tube formation can be reversed by DHA-treated with CM. Consistently, following DHA administration in a breast cancer mouse model, the number of transplanted tumor vessels was markedly reduced and perivascular cells increased. Subsequently, in vivo administration of DHA evidently promoted inhibitory effect of anti-PD-1 in tumor and reversed the infiltration of T cells and the phenotypes of macrophages. Network pharmacology and RNA-seq analysis revealed that DHA inhibit tumor growth by angiogenesis through the TNF-alpha pathway. Besides, TNF-alpha cytokine replenishment experiment and the expression of key molecules involved signaling pathway confirmed the above mechanism. In conclusion, DHA alleviates tumor cell-induced abnormal blood vessels through TNF-alpha pathway, which contributes to the anti-PD-1 efficacy of tumors.

关键词： 子宫内膜癌   病理特征   P16   Ki-67   相关性  

摘要： 目的:探讨子宫内膜癌(endometrial carcinoma,EC)病理特征与肿瘤抑制基因P16、肿瘤增殖抗原Ki-67 表达的相关性.方法:选取2022 年8 月至2024 年8 月本院收治的112 例EC患者为研究对象.取患者手术切除的病灶肿瘤组织纳入EC组,将其病灶旁边 5cm处正常组织纳入对照组.另选取同期 111 例子宫内膜不典型增生(endometrial atypical hyperplasia,EAH)患者的病灶组织纳入EAH组.对比 3 组样本P16、Ki-67 阳性表达情况;分析组织P16、Ki-67 表达与EC患者临床病理特征的关系;采用Pearson相关性分析EC组织中P16 与Ki-67 阳性表达的相关性.结果:3 组组织样本P16、Ki-67 阳性表达率比较:EC组>EAH组>对照组,差异均有统计学意义(P<0.05).P16 阳性率:TNM分期为Ⅲ～Ⅳ期>Ⅰ～Ⅱ期,Ki-67 阳性率:组织分级为G3>G2>G1,差异均有统计学意义(P<0.05);不同年龄、肌层浸润、淋巴结转移的 P16、Ki-67 阳性率比较,差异无统计学意义(P>0.05).经Pearson相关性分析,EC组织样本中P16 阳性表达与Ki-67 阳性表达呈正相关(P<0.05).结论:P16、Ki-67 在EC患者中呈高表达,其表达水平与EC临床病理分期、分级密切相关,可为EC临床诊疗提供依据.

摘要： 近年来,被蜜蜂、马蜂、蝎子等昆虫蜇伤,引发的严重过敏反应——Ⅰ型超敏反应病例呈现渐增趋势,显然,这与人们的过敏体质有很大关系.病人被蜇伤后,若不能得到及时确诊,实施针对性强的紧急治疗,往往会造成严重的后果,需要引起急诊科临床医生的高度重视.

关键词： depression   glucocorticoids   polyarthralgia   polychondritis   rheumatoid arthritis  

关键词： Nuclear factor kappa B activating protein (NKAP)   gastric cancer (GC)   nuclear factor kappa B (NF-kappa B)   interleukin-10 (IL-10)   immune escape  

摘要： Background: Gastric cancer (GC) remains a major clinical challenge due to its high mortality and propensity for immune escape, which critically limits the efficacy of immunotherapy. The immunosuppressive tumor microenvironment (TME) is a key factor restricting the effectiveness of immune checkpoint inhibitors (ICIs) in GC. The nuclear factor kappa B (NF-kappa B) activating protein (NKAP), a conserved regulator of the NF-kappa B pathway, has been shown to drive immune evasion in other cancer types by modulating cytokine networks and immune cell functions. However, the specific role and mechanisms of NKAP in shaping the immunosuppressive TME of GC and contributing to resistance against programmed death ligand 1 (PD-L1) blockade therapy remain largely unexplored. Therefore, this study aimed to investigate the role of NKAP in the GC TME and elucidate its mechanisms in driving immune escape and resistance to anti-PD-L1 therapy. Methods: We analyzed datasets from The Cancer Genome Atlas (TCGA) datasets and clinical specimens from patients with GC who received neoadjuvant therapy with PD-L1 inhibitors to evaluate NKAP expression and its association with clinicopathological features. In vitro models of mature dendritic cells (mDCs) and murine xenografts were used to investigate the mechanism underlying NKAP's involvement. NF-kappa B pathway activation, interleukin-10 (IL-10) secretion, and regulatory T cell (Treg) differentiation were assessed via luciferase assays, enzyme-linked immunosorbent assay, and flow cytometry. Changes in the TME and the therapeutic efficacy of PD-L1 blockade were evaluated in xenograft models. Results: Elevated NKAP expression correlated with advanced tumor-node-metastasis (TNM) stage, lymph node metastasis, and poor tumor differentiation in patients with GC. High NKAP levels predicted higher residual tumor burden post-PD-L1 therapy. Mechanistically, NKAP overexpression activated the NF-kappa B pathway in mDCs, driving IL-10 secretion and promotin

关键词： Leishmaniasis   Vaccine   Bioinformatic   Peptides   Immunogenicity   MHC I molecules   Leishmania infantum   L. donovani L. major  

摘要： Leishmaniasis, caused by protozoan parasites of the genus Leishmania, is a significant global health concern, with visceral leishmaniasis (VL) being its most severe clinical form. Current therapeutic options remain limited, beside of the urgent need for effective vaccines. This study identified and analyzed antigenic epitopes from Leishmania species that interact with class MHCI molecules and are recognized by T lymphocyte receptors. Peptide sequences from Leishmania species were selected from the Immune Epitope Database (IEDB) based on their interaction with MHCI molecules and ranked for immunogenicity using IEDB's predictive tools. Sequence similarities and conservation across Leishmania species were assessed using BLAST, and the peptides were synthesized via solid-phase peptide synthesis. Female BALB/c mice were immunized with the peptides, and their humoral responses were evaluated by measuring IgG titers in serum. This study identified ten peptides that, when incorporated into a vaccine construct, were capable of inducing high levels of IgG antibodies in an animal model. Among them, two stood out as immunodominant and potential targets for the development of novel vaccine strategies. These findings provide initial evidence of the potential of these peptides in developing new vaccines and therapeutic strategies against visceral leishmaniasis.

关键词： 宫颈癌   P53蛋白   P16蛋白   Ki-67  

摘要： 目的:探讨肿瘤抑制基因P53、P16 和增殖细胞核抗原Ki-67 在宫颈癌(CCA)组织中的表达与病理特征、预后的关系.方法:选取 2018 年 1 月至 2020 年 12 月本院收治的 102 例CCA患者作为研究对象.依据预后情况,将其分为预后良好组(n=59)和预后不良组(n=43).检测所有患者CCA组织标本中P53、P16、Ki-67 的表达情况,同时收集所有患者的病理特征资料,分析上述指标在CCA组织的表达与病理特征、预后的关系.结果:102 例CCA患者中,P53 阳性率为 44.12％(45/102),P16 阳性率为 71.57％(73/102),Ki-67 阳性率为 77.45％(79/102).疾病分期为Ⅱ期患者的P53 阳性率高于Ⅰ期,分化程度为低分化患者的P16 阳性率高于中高分化,有淋巴结转移(LNM)患者的P16、Ki-67 阳性率均高于无LNM,差异均有统计学意义(P<0.05).预后不良组患者P53、P16、Ki-67 阳性率高于预后良好组,差异均有统计学意义(P<0.05).结论:P53、P16、Ki-67 在CCA组织的表达与病理特征和预后存在明显关联性.

关键词： Beh & ccedil   et's syndrome   Monoclonal anti-TNF antibodies   Efficacy   meta-analysis  

摘要： Objectives: This study is the first meta-analysis to evaluate the efficacy and safety of monoclonal anti-TNF antibodies in patients with vascular Beh & ccedil;et's syndrome (VBS). Methods: A comprehensive literature search was conducted on PubMed, Embase, Cochrane Library, Medline Complete, and Web of Science. Pooled estimates of clinical response including complete response (CR) and partial response (PR), were calculated at 3, 6, and 12 months. Subgroup analyses were performed based on the specific monoclonal anti-TNF antibodies used. Additionally, pooled proportions of imaging response before and after 6 months were assessed. Results: Twelve studies involving 297 patients were included. The pooled proportions of clinical CR were 64.1 % (95 %CI 28.7-93.9 %), 89.1 % (95 %CI 72.4-98.6 %), and 94.5 % (95 %CI 82.5-99.8 %) at 3, 6, and 12 months, respectively. Imaging response was achieved in 92.9 % (95 %CI 77.2-100 %) of patients within 6 months and 92.5 % (95 %CI 74.8-99.9 %) after 6 months. During follow-up, 26 patients experienced a relapse while on monoclonal anti-TNF antibodies treatment. Of the 43 patients who discontinued therapy due to response, 28 % (n = 12) experienced a relapse. Adverse events (AEs) were reported in 10 studies involving 42 patients, with 31 patients experiencing severe AEs, including 5 deaths. Conclusions: Monoclonal anti-TNF antibodies are an effective treatment for VBS, demonstrating significant clinical and radiological efficacy with a favorable safety profile. Prevention of relapses and control of disease progression remain critical objectives in VBS management. Further validation of their efficacy through randomized controlled trials (RCTs) stratified by arterial and venous involvement is warranted to strengthen the evidence base and optimize therapeutic strategies.