edema

硬肿病
  • 文章类型: Journal Article
    探讨肿瘤周围水肿(PE)是否可以增强深度学习影像组学(DLR)模型预测乳腺癌腋窝淋巴结转移(ALNM)负担。回顾性纳入具有术前MRI的浸润性乳腺癌患者,并根据手术病理将其分为低(<2个淋巴结(LNs))和高(≥2个LNs)负荷组。PE在T2WI上进行评估,并在DCE-MRI中从MRI可见的肿瘤中提取肿瘤内和围肿瘤影像学特征。在训练队列中开发了用于LN负担预测的深度学习模型,并在独立队列中进行了验证。通过接收器工作特性(ROC)分析评估PE的增量值,使用Delong检验确认曲线下面积(AUC)的改善。这得到了净重新分类改进(NRI)和综合歧视改进(IDI)指标的补充。深度学习组合模型,将PE与选定的放射学特征相结合,在训练队列中,与MRI模型和DLR模型相比,AUC值明显更高(n=177)(AUC:0.953vs.0.849和0.867,p<0.05)和验证队列(n=111)(AUC:0.963vs.0.883和0.882,p<0.05)。互补分析表明,PE显著增强DLR模型的预测性能(分类NRI:0.551,p<0.001;IDI=0.343,p<0.001)。这些发现在验证队列中得到证实(分类NRI:0.539,p<0.001;IDI=0.387,p<0.001)。PE改良术前ALNM负荷预测的DLR模型,促进乳腺癌患者的个性化腋窝管理。
    To investigate whether peritumoral edema (PE) could enhance deep learning radiomic (DLR) model in predicting axillary lymph node metastasis (ALNM) burden in breast cancer. Invasive breast cancer patients with preoperative MRI were retrospectively enrolled and categorized into low (< 2 lymph nodes involved (LNs+)) and high (≥ 2 LNs+) burden groups based on surgical pathology. PE was evaluated on T2WI, and intra- and peri-tumoral radiomic features were extracted from MRI-visible tumors in DCE-MRI. Deep learning models were developed for LN burden prediction in the training cohort and validated in an independent cohort. The incremental value of PE was evaluated through receiver operating characteristic (ROC) analysis, confirming the improvement in the area under the curve (AUC) using the Delong test. This was complemented by net reclassification improvement (NRI) and integrated discrimination improvement (IDI) metrics. The deep learning combined model, incorporating PE with selected radiomic features, demonstrated significantly higher AUC values compared to the MRI model and the DLR model in the training cohort (n = 177) (AUC: 0.953 vs. 0.849 and 0.867, p < 0.05) and the validation cohort (n = 111) (AUC: 0.963 vs. 0.883 and 0.882, p < 0.05). The complementary analysis demonstrated that PE significantly enhances the prediction performance of the DLR model (Categorical NRI: 0.551, p < 0.001; IDI = 0.343, p < 0.001). These findings were confirmed in the validation cohort (Categorical NRI: 0.539, p < 0.001; IDI = 0.387, p < 0.001). PE improved preoperative ALNM burden prediction of DLR model, facilitating personalized axillary management in breast cancer patients.
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  • 文章类型: Case Reports
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  • 文章类型: Journal Article
    背景:TAFRO综合征是一种全身性炎症性疾病,表现为血小板减少症(t),anasarca(a),发烧(f),网织蛋白骨髓纤维化/肾功能不全(r),和器官肿大(o),并被认为是特发性多中心Castleman病(iMCD)的独特临床亚型。这种综合征引起的临床表现类似于结缔组织疾病或自身免疫性疾病。
    方法:一名中国年轻女性,最初表现为关节痛,雷诺现象,全身性水肿,抗小核核糖核蛋白颗粒抗体阳性被诊断为混合性结缔组织病。肾活检显示血栓性微血管病变。骨髓涂片显示骨髓增生,活检提示怀疑轻链限制性表达,巨核细胞增殖,和中度至重度骨髓纤维化。进行了淋巴结活检,组织病理学发现与混合型Castleman病的亚型一致。常规化疗后临床症状缓解。
    方法:经过以上检查结果和临床表现,最终诊断为TAFRO综合征.
    方法:她开始用硼替佐米化疗,环磷酰胺,还有地塞米松.
    结果:化疗后,血小板减少症等症状,血尿和蛋白尿消失,淋巴结肿大和VEGF水平下降,骨髓纤维化缓解。
    结论:我们的病例说明了第一例混合性结缔组织病和iMCD-TAFRO综合征的共同特征。细胞因子可能在iMCD-TAFRO综合征和全身性自身免疫性疾病的共同致病性中起作用。直接针对炎症因子如糖皮质激素或化疗的治疗具有重要的治疗意义。
    BACKGROUND: TAFRO syndrome is a systemic inflammatory disorder, manifesting as thrombocytopenia (t), anasarca (a), fever (f), reticulin myelofibrosis/renal insufficiency (r), and organomegaly (o), and considered as a unique clinical subtype of idiopathic multicentric Castleman disease (iMCD). Such syndrome gave rise to a clinical picture similar to that of either a connective tissue disease or an autoimmune disease.
    METHODS: A Chinese young female initially presenting with arthralgia, Raynaud phenomenon, generalized edema, and a positive anti-small nuclear ribonucleoprotein particle antibody was diagnosed as mixed connective tissue disease. The kidney biopsy showed thrombotic microangiopathy. Bone marrow smear showed bone marrow hyperplasia and biopsy revealed suspected light chain restricted expression, megakaryocyte proliferation, and moderate to severe bone marrow fibrosis. A lymph node biopsy was conducted and the histopathological findings were consistent with the subtype of mixed Castleman disease. The clinical symptoms were relieved after regular chemotherapy.
    METHODS: After above examination results and clinical manifestations, the final diagnoses was TAFRO syndrome.
    METHODS: The she was started on chemotherapy with bortezomib, cyclophosphamide, and dexamethasone.
    RESULTS: After chemotherapy, symptoms such as thrombocytopenia, hematuria and proteinuria disappeared, lymphadenopathy and VEGF level decreased, and bone marrow fibrosis relieved.
    CONCLUSIONS: Our case illustrated the first cases of shared characteristics of mixed connective tissue disease and iMCD-TAFRO syndrome. Cytokines may play a role in the shared pathogenicity of the iMCD-TAFRO syndrome and systemic autoimmune diseases. Therapy directly against inflammatory factors such as corticosteroids or chemotherapy have an important therapeutic implication.
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  • 文章类型: Case Reports
    A 31-year-old man sought medical evaluation for a 2-year history of edema and proteinuria, with prior pathology suggesting atypical membranous nephropathy (MN). Despite treatment with a combination of steroids, calcineurin inhibitors, and four courses of rituximab (1 g, intravenous injection), the patient\'s nephrotic syndrome showed no relief (24 h urine protein peaked at 31.18 g/d), indicating refractory nephrotic syndrome. Later in the disease course, a sudden surge of creatinine level (322.5 μmol/L) prompted a renal biopsy, which revealed concurrent acute interstitial nephritis. Further treatment involving steroids, cyclophosphamide, and a fifth rituximab infusion (1 g, intravenous injection) resulted in improvement in renal function (serum creatinine: 322.5➝147 μmol/L), but the MN failed to achieve partial relief. Subsequent treatment with the novel humanized CD20 monoclonal antibody obinutuzumab (1 g, intravenous injection) was initiated. In the latest follow-up, anti-phospholipase-A2-receptor antibody (PLA2R) antibody were negative, B cells were eliminated, serum albumin was 36 g/L, urine protein-to-creatinine ratio was 4 810 mg/g, and serum creatinine was 162 μmol/L. This case underscores the potential efficacy of obinutuzumab in refractory MN. For advanced MN cases, prompt identification of the cause of acute kidney injury is crucial, emphasizing the need for targeted interventions to potentially stall renal function decline.
    患者男性,31岁。因水肿、蛋白尿2年余就诊,外院肾脏病理提示不典型膜性肾病。糖皮质激素联合钙调磷酸酶抑制剂、4程利妥昔单抗(1 g,静脉输注)治疗后肾病综合征无缓解,24 h尿蛋白仍高达31.18 g,考虑为难治性肾病综合征。后期病程中短期内出现肌酐升高(322.5 μmol/L),重复肾组织活检病理示膜性肾病合并急性间质性肾炎,予足量糖皮质激素联合环磷酰胺加第5程利妥昔单抗1 g静脉输注,间质性肾炎导致的肾功能损害呈现缓解趋势(血肌酐322.5 μmol/L➝147 μmol/L),但膜性肾病仍未能部分缓解,随后尝试使用奥妥珠单抗(1 g,静脉输注)。患者门诊规律随诊,末次随访抗磷脂酶A2受体抗体阴性,B细胞清零,血白蛋白36 g/L,尿总蛋白肌酐比4 810 mg/g,血肌酐162 μmol/L。提示奥妥珠单抗在难治性膜性肾病中的疗效。此外,在肾病综合征的任何时期,合并急性肾损伤时均需要鉴别原因,寻找可逆因素并行针对性治疗,尽可能延缓肾功能恶化。.
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  • 文章类型: Journal Article
    慢性疼痛已经成为一个重要的公共卫生问题,严重影响患者的生活质量和心理健康,缺乏有效的药物治疗。大量研究表明,巨噬细胞在炎性疼痛中起着至关重要的作用,和靶向神经免疫相互作用的药物开发可能代表了疼痛管理的一个有希望的方向。Chilobrachysjinghao(C.jinghao)被用作黎族的民间药物,具有消肿的功效,解毒,缓解疼痛,相关产品在市场上得到广泛应用。然而,晶赵的化学成分尚未见报道,药效物质和确切的作用机制尚未揭示。在这里我们分离了一个环状二肽,cyclo(L-Pro-L-Trp)(CPT)首次从C.jingzhao.CPT可显着减轻福尔马林诱导的炎性疼痛并显着抑制炎症反应。在体内,CPT减轻了中性粒细胞浸润和足底组织水肿,并抑制了促炎分子的mRNA表达。体外,CPT在RAW264.7和iBMDM细胞中抑制由脂多糖(LPS)引发的炎症,减少诱导型一氧化氮合酶(iNOS)的表达,超氧化物,和促炎分子。一项机制研究表明,CPT通过阻断丝裂原活化蛋白激酶(MAPK)和核因子-κB(NF-κB)信号通路发挥抗炎活性,以及减轻肿瘤坏死因子受体相关因子6(TRAF6)的泛素化。我们的研究结果阐明了C.jingzhao的药效学物质基础,和CPT可以是缓解炎症和炎性疼痛的有希望的线索。
    Chronic pain has emerged as a significant public health issue, seriously affecting patients\' quality of life and psychological well-being, with a lack of effective pharmacological treatments. Numerous studies have indicated that macrophages play a crucial role in inflammatory pain, and targeting neuro-immune interactions for drug development may represent a promising direction for pain management. Chilobrachys jingzhao (C. jingzhao) is used as a folk medicine of the Li nationality with the efficacy of eliminating swelling, detoxicating, and relieving pain, and the related products are widely used in the market. However, the chemical constituents of C. jingzhao have not been reported, and the pharmacodynamic substance and the precise functional mechanism are unrevealed. Here we isolated a cyclic dipeptide, cyclo(L-Pro-L-Trp) (CPT) from C. jingzhao for the first time. CPT remarkably alleviated formalin-induced inflammatory pain and significantly inhibited inflammatory responses. In vivo, CPT attenuated neutrophil infiltration and plantar tissue edema and suppressed the mRNA expression of pro-inflammatory molecules. In vitro, CPT suppressed inflammation triggered by lipopolysaccharide (LPS) in both RAW 264.7 and iBMDM cells, reducing expressions of inducible nitric oxide synthase (iNOS), superoxide, and pro-inflammatory molecules. A mechanistic study revealed that CPT exerted an anti-inflammatory activity by blocking the mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, as well as alleviating the ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6). Our results elucidated the pharmacodynamic material basis of C. jingzhao, and CPT can be a promising lead for alleviating inflammation and inflammatory pain.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    背景:当归(AS)和川芎(CR)在临床环境中经常被规定为具有丰富血液的能力,调节月经周期,减轻疼痛。尽管它们广泛使用,对其抗炎特性的研究相对缺乏。
    目的:评价当归川芎提取物的抗氧化和抗炎作用,并探讨其抗炎作用机制。
    方法:AS和CR以六种比例混合,并使用五种溶剂提取。通过使用HPLC测定阿魏酸(FA)的含量来评估所得ASCR提取物的质量。使用DPPH和ABTS测定体外评估ASCR提取物的抗氧化作用,以及暴露于H2O2诱导的氧化损伤的HUVECs。此外,通过小鼠耳水肿和大鼠爪水肿的测定,在体内研究了提取物的抗炎作用。生化标志物包括NO,MDA,和SOD在爪组织中,以及PGE2,TNF-α,和大鼠血清中的COX-2,进行测量以进一步阐明ASCR提取物的抗炎机制。
    结果:WA-2-1是通过先用水再进行乙醇提取,以2:1的比例组合AS和CR而获得的,并表现出良好的抗氧化和抗炎活性。提取物表现出对DPPH·和ABTS·自由基的有效清除能力,同时还可以抵抗H2O2诱导的氧化损伤。此外,体内研究表明,WA-2-1对耳和爪水肿有显著的抑制作用,以及降低NO和MDA水平的能力,增强SOD活性,下调COX-2、PGE2和TNF-α的表达。
    结论:AS和CR的组合表现出良好的抗炎作用,归因于其减轻氧化应激和抑制炎症过程中血清或组织中炎症介质的产生的双重作用。
    BACKGROUND: Angelica sinensis (AS) and Chuanxiong rhizoma (CR) are frequently prescribed in clinical settings for their ability to enrich blood, regulate menstrual cycles, and alleviate pain. Despite their widespread use, there is a relative dearth of studies exploring their anti-inflammatory properties.
    OBJECTIVE: To evaluate the antioxidant and anti-inflammatory effects of Angelica sinensis-Chuanxiong rhizoma (ASCR) extracts and investigate its anti-inflammatory mechanisms.
    METHODS: AS and CR were combined in six ratios and extracted using five solvents. The quality of the resulting ASCR extracts was assessed by determining the content of ferulic acid (FA) using HPLC. The antioxidant effects of the ASCR extracts were evaluated in vitro using the DPPH and ABTS assays, as well as in HUVECs exposed to H2O2-induced oxidative damage. Additionally, the anti-inflammatory effects of the extracts were investigated in vivo through the assays of ear edema in mice and paw edema in rats. Biochemical markers including NO, MDA, and SOD in paw tissues, as well as PGE2, TNF-α, and COX-2 in rat serum, were measured to further elucidate the anti-inflammatory mechanisms of ASCR extracts.
    RESULTS: The WA-2-1 was obtained by combining AS and CR in a 2:1 ratio through first water then ethanol extraction, and showed favorable antioxidant and anti-inflammatory activities. The extract demonstrated effective scavenging abilities against DPPH• and ABTS+• radicals while also protecting against H2O2-induced oxidative damage. Furthermore, in vivo studies revealed that WA-2-1 had significant inhibitory effects on ear and paw edema as well as the ability to decrease NO and MDA levels, enhance SOD activity, and downregulate the expression of COX-2, PGE2, and TNF-α.
    CONCLUSIONS: The combination of AS and CR exhibits favorable anti-inflammatory effects, attributed to its dual actions of mitigating oxidative stress and suppressing the production of inflammatory mediators in serum or tissues during the inflammatory process.
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  • 文章类型: Case Reports
    背景:色素沉着绒毛结节性滑膜炎(PVNS)是一种影响滑膜关节的良性增生性疾病,法氏囊,和肌腱鞘.迄今为止,很少有研究报道PVNS患者术后疼痛和水肿的治疗。在这里,我们介绍了一例女性,在滑膜切除术和关节镜下半月板部分切除术后1周出现左下肢疼痛和水肿,由于左膝屈伸受限而无法行走。
    方法:一名32岁妇女先后接受了滑膜切除术和关节镜下半月板部分切除术,并在我院接受了手动淋巴引流(MLD)和运动贴膜(KT)的联合治疗,以减轻术后疼痛和水肿。在治疗后2周和出院后1周随访时评估以下参数:髌上围,髌下圆周,视觉模拟量表评分,膝盖的运动范围,匹兹堡睡眠质量指数评分,汉密尔顿焦虑量表(HAMA)评分,和汉密尔顿抑郁量表(HAMD)评分。治疗后,术后患者左膝关节疼痛及水肿得到有效缓解,改善睡眠质量,显著降低HAMA和HAMD评分。
    结论:MLD和KT联合应用可能是缓解PVNS患者术后疼痛和水肿的有效方法。
    BACKGROUND: Pigmented villonodular synovitis (PVNS) is a benign proliferative disorder that affects the synovial joints, bursae, and tendon sheaths. To date, few studies have reported on the treatment of postoperative pain and edema in patients with PVNS. Herein, we present the case of a woman who developed pain and edema in the left lower limb 1 wk after synovectomy and arthroscopic partial meniscectomy and was unable to walk due to limited flexion and extension of the left knee.
    METHODS: A 32-year-old woman underwent synovectomy and arthroscopic partial meniscectomy successively and was treated with a combination of manual lymphatic drainage (MLD) and kinesio taping (KT) in our hospital to alleviate postoperative pain and edema. The following parameters were assessed at 2 wk post-treatment and 1 wk post-discharge follow up: suprapatellar circumference, infrapatellar circumference, visual analog scale score, knee range of motion, pittsburgh sleep quality index score, hamilton anxiety rating scale (HAMA) score, and hamilton depression rating scale (HAMD) score. After treatment, the postoperative pain and edema in the patient\'s left knee were effectively relieved, resulting in improved sleep quality and remarkably attenuated HAMA and HAMD scores.
    CONCLUSIONS: Combined MLD and KT may be an effective approach for relieving postoperative pain and edema in patients with PVNS.
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  • 文章类型: Journal Article
    目的:本研究的目的是探讨上第三磨牙周围软组织的炎症是张口受限的主要原因,确定临床和影像学特征,总结拔牙的治疗效果。
    方法:对过去5年中264例张口受限患者的数据进行回顾性分析。
    结果:在264名患者中,24例(9.1%)上第三磨牙周围软组织有炎症,这是张口受限的第二大常见原因。二十四个受影响的病人中有二十一个,平均开口为19.1±7.6毫米,进行上第三磨牙提取。上颌第三磨牙或上颌结节粘膜周围的牙龈压痛是特征性的临床表现(p<0.05)。颌面部CT的特征性特征包括上第三磨牙周围的软组织肿胀和上颌结节与下颌升支之间的间隙变窄。提取后,平均张口增加到31.4±4.9mm(p<0.05),和随访CT显示上第三磨牙周围的炎性软组织消退。
    结论:上第三磨牙周围软组织的炎症是张口受限的常见原因。与上第三磨牙相关的疼痛症状和增强颌面CT扫描的独特发现对于诊断至关重要。上第三磨牙拔除产生有利的治疗结果。
    结论:上颌第三磨牙周围软组织的炎症通常会导致张口受限,但是这种现象长期以来一直被忽视。明确这种病因可以减少张口受限的误诊患者的数量,并为患者提供更有效的治疗。
    OBJECTIVE: The aim of this study was to explore inflammation of soft tissue around the upper third molar as a prevalent cause of limited mouth opening, identify the clinical and radiographic features, and summarize the therapeutic effectiveness of tooth extraction.
    METHODS: A retrospective analysis of data from 264 patients with limited mouth opening over the last five years was performed.
    RESULTS: Among the 264 patients, 24 (9.1%) had inflammation of the soft tissue around the upper third molar, which was the second most common cause of limited mouth opening. Twenty-one of the twenty-four affected patients, with an average mouth opening of 19.1 ± 7.6 mm, underwent upper third molar extraction. Gingival tenderness around the upper third molar or maxillary tuberosity mucosa was a characteristic clinical manifestation (p < 0.05). The characteristic features on maxillofacial CT included soft tissue swelling around the upper third molar and gap narrowing between the maxillary nodules and the mandibular ascending branch. Post extraction, the average mouth opening increased to 31.4 ± 4.9 mm (p < 0.05), and follow-up CT demonstrated regression of the inflammatory soft tissue around the upper third molar.
    CONCLUSIONS: Inflammation of soft tissue around the upper third molar is a common cause of limited mouth opening. Symptoms of pain associated with the upper third molar and distinctive findings on enhanced maxillofacial CT scans are crucial for diagnosis. Upper third molar extraction yields favorable therapeutic outcomes.
    CONCLUSIONS: Inflammation of the soft tissue around the maxillary third molar commonly causes limited mouth opening, but this phenomenon has long been overlooked. Clarifying this etiology can reduce the number of misdiagnosed patients with restricted mouth opening and enable more efficient treatment for patients.
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  • 文章类型: Journal Article
    背景:野菊花(FCI),菊花的花,是一种在中国流行的治疗炎症性疾病的中药(TCM)。FCI也是一种功能性食品,并被广泛用作清热解毒的凉茶。
    目的:基于最佳采收期,探索FCI的质量控制标记。
    方法:首先,基于UPLC-Q-TOF/MS的非靶向代谢组学应用于探索在芽阶段(BS)收集的FCI的化学概况,初始阶段(IS),中国八个耕地的盛开阶段(FS)和最终阶段(ES)。随后,脂多糖(LPS)诱导的RAW264.7细胞炎症模型和角叉菜胶诱导的大鼠爪水肿模型用于证实在IS/FS收集的FCI的抗炎作用。然后,采用UPLC-PDA靶向代谢组学方法对开花期9种具有抗炎活性的成分(7种黄酮类化合物和2种酚酸)进行定量分析(VIP>4)。最后,根据不同开花期FCI中9种活性成分的变化,将ROC曲线结合PCA分析用于筛选FCI的质量标记。
    结果:IS/FS处的FCI具有几乎相同的化学特性,但与BS和ES的完全不同。在开花发育过程中,FCI中共有32种成分发生了变化,包括类黄酮和酚酸。与ES相比,IS/FS下大多数不同成分的含量最高或更高,表明FCI的最佳收获期应为IS/FS。FCI提取物可以有效抑制LPS诱导的RAW264.7细胞中一氧化氮(NO)的产生,并调节角叉菜胶诱导的爪水肿模型大鼠细胞因子和PGE2的异常水平。定量分析结果表明,在开花发育过程中,FCI中酚酸和黄酮的变化趋势不同,但在从八个栽培区收集的所有FCI中,大多数在IS/FS的含量高于ES的含量,除了TC,安徽。最后,linarin,木犀草素,根据其AUC值在ROC中的贡献和PCA分析的聚类,选择芹菜素和3,5-二咖啡酰基奎尼酸作为Q标记。
    结论:我们的研究证明了FCI的最佳收获期,并根据生长进程对活性成分的影响,使用非靶向/靶向代谢组学确定了FCI的多成分Q标记。研究结果不仅大大提高了FCI资源的利用率,提高了FCI产品的质量控制,而且还提供了新的策略来识别FCI的Q标记。
    BACKGROUND: Flos Chrysanthemi Indici (FCI), the flower of Chrysanthemum Indicum L., is a popular traditional Chinese medicine (TCM) for treatment of inflammatory diseases in China. FCI is also a functional food, and is widely used as herbal tea for clearing heat and detoxicating.
    OBJECTIVE: To explore quality control markers of FCI based on the optimal harvest period.
    METHODS: First, UPLC-Q-TOF/MS based untargeted metabolomics was applied to explore the chemical profiles of FCIs collected at bud stages (BS), initial stages (IS), full bloom stages (FS) and eventual stages (ES) from eight cultivated regions in China. Subsequently, lipopolysaccharide (LPS)-induced RAW264.7 cell inflammatory model and carrageenan-induced rat paw edema model were used to confirm the anti-inflammatory effect of FCIs collected at IS/FS. Then, UPLC-PDA targeted metabolomics was used to quantitatively analyze 9 constituents with anti-inflammatory activity (7 flavonoids and 2 phenolic acids) changed significantly (VIP > 4) during flowering stages. Finally, ROC curves combined with PCA analysis based on the variation of 9 active constituents in FCIs from different flowering stages were applied to screen the quality markers of FCI.
    RESULTS: FCIs at IS/FS had almost same chemical characteristics, but quite different from those at BS and ES. A total of 32 constituents in FCIs including flavonoids and phenolic acids were changed during flowering development. Most of the varied constituents had the highest or higher contents at IS/FS compared with those at ES, indicating that the optimal harvest period of FCI should be at IS/FS. FCI extract could effectively suppress nitric oxide (NO) production in LPS-induced RAW264.7 cells and regulate the abnormal levels of cytokines and PGE2 in carrageenan-induced paw edema model rat. The results of quantitatively analysis revealed that the variation trends of phenolic acids and flavonoids in FCIs were different during flowering development, but most of them had higher contents at IS/FS than those at ES in all FCIs collected from eight cultivated regions, except one sample from Anhui. Finally, linarin, luteolin, apigenin and 3,5-dicaffeoylquinic acid were selected as the Q-markers based on the contribution of their AUC values in ROC and clustering of PCA analysis.
    CONCLUSIONS: Our study demonstrates the optimal harvest period of FCI and specifies the multi-constituents Q-markers of FCI based on the influence of growth progression on the active constituents using untargeted/targeted metabolomics. The findings not only greatly increase the utilization rate of FCI resources and improve quality control of FCI products, but also offer new strategy to identify the Q-markers of FCI.
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