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关键词： biomarkers   cortisol   death acceptance   existential attitudes   IL-12   life control   life purpose   noradrenaline   posttraumatic stress disorder   serotonin  

摘要： Posttraumatic Stress Disorder (PTSD) is characterized by disruptions in central nervous system functioning and existential crises, yet the mechanistic links between neurobiological processes and dimensions of life meaning and identity remain underexplored. The aim of this study was to examine the relationships between stress biomarkers (serotonin, cortisol, noradrenaline, and interleukin-12 [IL-12]) and existential attitudes (measured using the Life Attitude Profile (Revised) [LAP-R]) in mining rescuers, considering PTSD duration and participant age. This cross-sectional study included 92 men aged 18-50 years, divided into three groups: no PTSD (n = 28), PTSD <= 5 years (n = 33), and PTSD > 5 years (n = 31). Serum levels of four biomarkers and LAP-R scores across eight domains were evaluated. Statistical analyses employed nonparametric tests, including the Kruskal-Wallis test for overall group differences (with Wilcoxon r effect sizes for pairwise comparisons, Mann-Whitney U tests for post hoc pairwise comparisons, and Spearman's rank correlations for biomarker-LAP-R associations. Age effects were assessed in two strata: 18-35 years and 36-50 years. Kruskal-Wallis tests revealed significant group differences (p < 0.001) for all biomarkers and most LAP-R domains, with very large effect sizes (r > 0.7) in pairwise comparisons for serotonin (control median: 225.2 ng/mL vs. PTSD <= 5y: 109.9 ng/mL, r = 0.86;vs. PTSD > 5y: 148.0 ng/mL, r = 0.86), IL-12 (control: similar to 8.0 pg/mL vs. PTSD <= 5y: 62.4 pg/mL, r = 0.86;vs. PTSD > 5y: similar to 21.0 pg/mL, r = 0.69), and LAP-R scales such as Life Purpose (control: 54.0 vs. PTSD <= 5y: 39.0, r = 0.78;vs. PTSD > 5y: 20.0, r = 0.86) and Coherence (control: 53.0 vs. PTSD <= 5y: 34.0, r = 0.85;vs. PTSD > 5y: 23.0, r = 0.86). The PTSD <= 5y group exhibited decreased serotonin, cortisol (median: 9.8 mu g/dL), and noradrenaline (271.7 pg/mL) with elevated IL-12 (all p < 0.001 vs. control), alongside reduced LAP-R scores. The PTS

关键词： Desmethylglycitein   Memory   Alzheimer's disease   Oxidative stress   Nrf-2   IL-1 beta  

摘要： Alzheimer's disease constitutes a progressive brain-destroying disorder that leads people to lose memory abilities while experiencing behavioral modifications and gradual mental deterioration. The worldwide population affected by AD stands at 50 million individuals. The current treatments provide symptomatic relief instead of therapeutically treating the altered neurological processes. Plant-derived compounds have demonstrated promising neuroprotective effects by modulating key pathways implicated in neurodegenerative diseases. The present research evaluated the potential of desmethylglycitein against scopolamine-induced cognitive impairment in mice. Desmethylglycitein is a naturally occurring isoflavone, primarily found in soy products and other leguminous plants. The research period lasted for 9 days, during which desmethylglycitein (10, 20 and 40 mg/kg) or donepezil (5 mg/kg) was administered. Scopolamine (2 mg/kg) was given on days 7-9. Behavioral tests (MWM, Y-maze and OFT) were performed on days 7 and 9, followed by biochemical analyses. Scopolamine treatment significantly impaired memory and locomotor activity. The memory impairment caused by scopolamine was significantly alleviated by desmethylglycitein, as evidenced by reduced escape latencies in MWM and increased percentage of spontaneous alternation in Y-maze. Desmethylglycitein treatment also improved locomotor activity in the OFT as evidenced by an increased number of square crossings. In the biochemical analysis, scopolamine treatment significantly decreased brain GSH levels and increased brain TBARS levels. Furthermore, it reduced serum Nrf-2 levels and elevated serum IL-1 beta levels. Pretreatment with desmethylglycitein significantly mitigated these biochemical changes induced by scopolamine. This suggests that desmethylglycitein may have the potential to counteract scopolamine-induced deficits in memory and locomotion, possibly by inhibiting oxidative and inflammatory stress.

关键词： allele variant   next generation sequencing   novel allele  

摘要： The novel allele HL A- B*50:01:01:14 displays a single polymorphism in the 5 ' UTR when compared to HL A- B*50:01:01:01

关键词： Naphthalene  

摘要： A multi-target and molecular hybridization drug design approach was used in the design and synthesis of novel 6-acetylnaphthalene-2-sulfonamide derivatives (5a-5j) for anticancer and antimicrobial evaluation. The compounds 5a, 5b, 5e, and 5i revealed the most cytotoxic activity against the human breast cancer cell line (MCF7) with a good safety profile against the normal Madin-Darby canine kidney cell line (MDCK). Compounds 5b and 5i exhibited significant antiproliferative activity in MCF7 cells by downregulating IL6, JAK2, STAT3, BCL2, Cyclin D1, and c-MYC, while upregulatiing BAX expression levels, relative to control values, as confirmed by qRT-PCR analysis. Moreover, the antibacterial and anti-mycotic activities for 5a-5j were assessed, and the minimum inhibitory concentration (MIC) was evaluated for the promising compounds. In in vitro enzymatic assays, compounds 5e and 5b potently inhibited STAT3 phosphorylation with IC50 = 3.01 mu M and 3.59 mu M, respectively, compared with cryptotanshinone (IC50 = 3.52 mu M);compound 5b potently inhibited topoisomerase IV (IC50 = 5.3 mu g mL-1, norfloxacin IC50 = 8.24 mu g mL-1) and moderately inhibited DNA gyrase in E. coli;and compound 5e effectively inhibited topoisomerase IV (IC50 = 7.65 mu g mL-1, norfloxacin IC50 = 7.07 mu g mL-1) and moderately inhibited DNA gyrase in S. aureus. Finally, SAR was discussed, revealing the essential role of the N-aryl and/or heteroaryl moiety in directing the biological activity of each compound towards a specific target. An in silico study was performed to predict ADME and docking for the promising hybrids. Collectively, the 6-acetylnaphthalene-2-sulfonamide hybrids suppressed MCF7 cell proliferation and induced apoptosis via modulation of the IL6/JAK2/STAT3 signaling pathway and representing promising building blocks as STAT3 inhibitors and antimicrobial leads for future modifications.

关键词： span>Immune-evasive iPSC therapywhole blood extracorporeal circulationsystemic inflammation resolutionhepatocyte nuclear factor 4 alpha (HNF4α)alginate-encapsulationliver regeneration  

关键词： Crohn's disease-like lesions   Necrotizing enterocolitis   Anastomotic ulcer   Anti-TNF therapy   Adalimumab  

摘要： BackgroundDigestive perianastomotic ulcerations (DPAU) are rare Crohn's disease (CD)-like lesions that develop following intestinal surgery. Although enteral nutrition and anti-inflammatory agents constitute first-line therapies, 59% of refractory cases require advanced interventions. Emerging evidence implicates tumor necrosis factor (TNF)-alpha-driven inflammation as a key pathogenic mechanism, yet optimal therapeutic strategies remain *** summaryA 12-year-old girl with a surgery history of neonatal necrotizing enterocolitis (NEC) presented with severe anemia (hemoglobin: 51 g/L) and chronic abdominal pain. Endoscopy revealed circumferential ulcers at the ileocolonic anastomosis, histologically confirmed as active inflammation without granulomas or evidence of infections. Initial therapy with 3 months enteral nutrition and mesalamine failed. Subcutaneous adalimumab induced endoscopic ulcer healing and hemoglobin normalization (111 g/L) within 3 months. At the 12-month follow-up, sustained clinical remission was observed (hemoglobin: 120 g/L, fecal calprotectin: 45 mu g/g), with complete mucosal healing and no adverse *** anti-TNF therapy induced rapid and sustained remission in a pediatric patient with DPAU, reinforcing the mechanism that TNF-alpha-driven inflammation underlies disease pathogenesis. While promising, these findings require validation in larger cohorts. Individualized therapeutic decisions should weigh the risks of recurrence, cost, and long-term biologic safety.

关键词： 肺移植   补体抑制剂   原发性移植物功能障碍   抗体介导的排斥反应   慢性移植肺功能障碍   C5抑制剂   依库珠单抗   C1酯酶抑制剂  

摘要： 肺移植是治疗终末期肺病的唯一有效手段,但其长期预后受到早期及晚期并发症影响,如原发性移植物功能障碍、抗体介导的排斥反应及慢性移植肺功能障碍等。近年来,补体系统在上述病理过程中所发挥的核心作用逐渐受到重视。作为一类新型免疫调节策略,补体抑制剂在肺移植中尚处于探索阶段。因此,本文就补体系统在原发性移植物功能障碍、抗体介导的排斥反应及慢性移植肺功能障碍中的病理机制进行综述,结合现有临床案例,分析补体抑制剂在改善肺移植物功能中的潜在作用及局限性,并提出未来研究的方向与建议,旨在为肺移植并发症的精准干预,改善肺移植预后提供参考。

关键词： 补体系统   喉鳞状细胞癌   肿瘤微环境   上皮间质转化  

摘要： 补体系统是免疫系统的重要组成部分,参与多种疾病,如自身免疫性疾病、感染性疾病、风湿性疾病、血液系统疾病和癌症的发生及发展。喉癌是常见的头颈部恶性肿瘤之一,研究补体影响喉鳞状细胞癌相关机制,并从中寻找有效的生物标志物,将有助于提高对喉鳞状细胞癌的诊断、治疗能力。本文简要综述补体系统的激活,并从肿瘤微环境、肿瘤细胞本身及其分泌物层面阐述了补体蛋白如何影响喉鳞状细胞癌发生发展及转移,为进一步研究喉鳞癌靶向治疗的临床应用提供参考。