• 文章类型: Journal Article
    本研究的目的是探讨异位脑胺的保护作用和潜在机制,一种天然的渗透保护剂,干眼症眼表粘蛋白的产生。
    在暴露于干燥应激(DS)的C57BL/6小鼠中建立干眼模型,未处理(UT)小鼠作为对照。DS小鼠用2.0%艾克托因或PBS载体局部处理。通过俄勒冈绿葡聚糖(OGD)荧光染色评估角膜上皮缺损。结膜杯状细胞,眼粘蛋白,和T帮助(Th)细胞因子通过免疫荧光染色或ELISA进行评估,和RT-qPCR。
    与UT小鼠相比,角膜上皮缺损被检测为强点OGD荧光染色DS小鼠与载体,而ectoine治疗将OGD染色大大降低至接近正常水平。DS小鼠结膜杯状细胞密度和细胞大小明显下降,但通过艾克托因治疗显着恢复。两种凝胶分泌型MUC5AC和MUC2的蛋白质产生和mRNA表达,以及4种跨膜粘蛋白,MUC1,MUC4,MUC16和MUC15在DS小鼠中大幅下降,但是被ectoine修复了。此外,Th2细胞因子IL-13被抑制,而Th1细胞因子IFN-γ在DS小鼠的结膜和引流颈淋巴结(CLN)中的蛋白质和mRNA水平受到刺激,导致IL-13/IFN-γ比值降低。有趣的是,2.0%的埃托因逆转了它们的交替,并恢复了IL-13/IFN-γ平衡。
    我们的研究结果表明,外用外用能显著减少角膜损伤,并通过恢复小鼠干眼模型中不平衡的IL-13/IFN-γ信号传导来增强杯状细胞密度和粘蛋白产生。这表明天然渗透保护剂艾托因治疗干眼病的潜力。
    UNASSIGNED: This study aimed to explore protective effects and potential mechanism of ectoine, a natural osmoprotectant, on ocular surface mucin production in dry eye disease.
    UNASSIGNED: A dry eye model was established in C57BL/6 mice exposed to desiccating stress (DS) with untreated (UT) mice as controls. DS mice were topically treated with 2.0% ectoine or PBS vehicle. Corneal epithelial defects were assessed by Oregon Green Dextran (OGD) fluorescent staining. Conjunctival goblet cells, ocular mucins, and T help (Th) cytokines were evaluated by immunofluorescent staining or ELISA, and RT-qPCR.
    UNASSIGNED: Compared with UT mice, corneal epithelial defects were detected as strong punctate OGD fluorescent staining in DS mice with vehicle, whereas ectoine treatment largely reduced OGD staining to near-normal levels. Conjunctival goblet cell density and cell size decreased markedly in DS mice, but was significantly recovered by ectoine treatment. The protein production and mRNA expression of two gel-forming secreted MUC5AC and MUC2, and 4 transmembrane mucins, MUC1, MUC4, MUC16, and MUC15, largely decreased in DS mice, but was restored by ectoine. Furthermore, Th2 cytokine IL-13 was inhibited, whereas Th1 cytokine IFN-γ was stimulated at protein and mRNA levels in conjunctiva and draining cervical lymph nodes (CLNs) of DS mice, leading to decreased IL-13/IFN-γ ratio. Interestingly, 2.0% ectoine reversed their alternations and restored IL-13/IFN-γ balance.
    UNASSIGNED: Our findings demonstrate that topical ectoine significantly reduces corneal damage, and enhances goblet cell density and mucin production through restoring imbalanced IL-13/IFN-γ signaling in murine dry eye model. This suggests therapeutic potential of natural osmoprotectant ectoine for dry eye disease.
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  • 文章类型: Journal Article
    针对干燥综合征(SS)的靶向治疗已成为临床医生的重要关注点。多组学广泛的孟德尔随机化(MR)分析为识别潜在的药物靶标提供了新思路。
    我们进行了基于汇总数据的孟德尔随机化(SMR)分析,以通过整合DNA甲基化来评估与SS相关的治疗靶标,基因表达和蛋白质数量性状基因座(mQTL,eQTL,和pQTL,分别)。与SS的遗传关联来源于FinnGen研究(发现)和GWAS目录(复制)。采用共定位分析来确定两种潜在相关表型在给定区域中是否共享相同的遗传因素。此外,深入研究DNA甲基化之间的潜在调控,基因表达,和蛋白质丰富,我们进行了MR分析,以探讨候选基因甲基化与表达之间的因果关系,以及基因表达和蛋白质丰度之间。进一步采用药物预测和分子对接来验证候选药物靶标的药理活性。
    在整合多组数据后,我们确定了与SS风险相关的三个基因:TNFAIP3,BTN3A1和PLAU.BTN3A1中cg22068371的甲基化与蛋白水平呈正相关,与cg22068371甲基化对SS风险的负面影响一致。此外,PLAU(cg04939496)基因甲基化与表达呈正相关,以及表达和蛋白质水平之间。这种一致性阐明了PLAU在DNA甲基化时对SS风险的促进作用,基因表达,和蛋白质水平。在蛋白质水平,遗传预测的TNFAIP3(OR2.47,95%CI1.56-3.92)与SS风险呈正相关,而BTN3A1(OR2.96E-03,95%CI2.63E-04-3.33E-02)与SS风险呈负相关。分子对接显示候选药物和靶蛋白的稳定结合。
    我们的研究揭示了治疗SS的有希望的治疗目标,为SS的靶向治疗提供有价值的见解。然而,有必要通过未来的实验进一步验证.
    UNASSIGNED: Targeted therapy for Sjögren\'s syndrome (SS) has become an important focus for clinicians. Multi-omics-wide Mendelian randomization (MR) analyses have provided new ideas for identifying potential drug targets.
    UNASSIGNED: We conducted summary-data-based Mendelian randomization (SMR) analysis to evaluate therapeutic targets associated with SS by integrating DNA methylation, gene expression and protein quantitative trait loci (mQTL, eQTL, and pQTL, respectively). Genetic associations with SS were derived from the FinnGen study (discovery) and the GWAS catalog (replication). Colocalization analyses were employed to determine whether two potentially relevant phenotypes share the same genetic factors in a given region. Moreover, to delve deeper into potential regulation among DNA methylation, gene expression, and protein abundance, we conducted MR analysis to explore the causal relationship between candidate gene methylation and expression, as well as between gene expression and protein abundance. Drug prediction and molecular docking were further employed to validate the pharmacological activity of the candidate drug targets.
    UNASSIGNED: Upon integrating the multi-omics data, we identified three genes associated with SS risk: TNFAIP3, BTN3A1, and PLAU. The methylation of cg22068371 in BTN3A1 was positively associated with protein levels, consistent with the negative effect of cg22068371 methylation on the risk of SS. Additionally, positive correlations were observed between the gene methylation of PLAU (cg04939496) and expression, as well as between expression and protein levels. This consistency elucidates the promotional effects of PLAU on SS risk at the DNA methylation, gene expression, and protein levels. At the protein level, genetically predicted TNFAIP3 (OR 2.47, 95% CI 1.56-3.92) was positively associated with SS risk, while BTN3A1 (OR 2.96E-03, 95% CI 2.63E-04-3.33E-02) was negatively associated with SS risk. Molecular docking showed stable binding for candidate drugs and target proteins.
    UNASSIGNED: Our study reveals promising therapeutic targets for the treatment of SS, providing valuable insights into targeted therapy for SS. However, further validation through future experiments is warranted.
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  • 文章类型: Journal Article
    目的:探讨原发性获得性鼻泪管阻塞(PANDO)患者干眼(DE)的患病率和泪膜稳定性的变化。
    方法:在此横截面中,观察性研究,对223例PANDO患者的370只眼进行了评估。眼表疾病指数(OSDI)用于评估眼表症状,并使用角膜摄影5M无创眼表分析仪评估眼表参数。根据TFOSDEWSII标准,OSDI≥13且NIKBUT<10s的患者被诊断为DE。
    结果:在223名PANDO患者中,65(29.1%)符合DE的诊断标准。与没有DE的患者相比,患有DE的PANDO患者明显年龄较大(p<0.001),有一个较长的持续时间的溢泪(p=0.023),并且更可能对泪囊压力(ROPLAS)信号(p=0.003)有正反流。多因素分析表明,年龄较大,ROPLAS阳性和高血压是DE的显著独立预测因子(p<0.05)。在147例无DE的单侧PANDO患者中,TMH,NIKBUT-First,PANDO两侧的NIKBUT平均和球红斑评分明显较高。
    结论:这项研究表明,在PANDO患者中,DE的患病率为29.1%,并且在年龄较大的患者中更容易发生,有高血压,ROPLAS阳性。此外,单侧鼻泪管阻塞的患者,在健康眼睛中观察到泪膜稳定性降低。
    OBJECTIVE: Exploring the prevalence of dry eye (DE) and the changes of tear film stability in patients with primary acquired obstruction of the nasolacrimal duct (PANDO).
    METHODS: In this cross-sectional, observational study, 370 eyes in 223 patients with PANDO were assessed. The ocular surface disease index (OSDI) was used to evaluate ocular surface symptoms, and the Keratograph 5M non-invasive ocular surface analyser was used to assess ocular surface parameters. According to the TFOS DEWS II criteria, patients with OSDI ≥ 13 and NIKBUT < 10 s were diagnosed with DE.
    RESULTS: Of the 223 PANDO patients, 65 (29.1%) met the diagnostic criteria for DE. Compared with patients without DE, PANDO patients with DE were significantly older (p < 0.001), had a longer duration of epiphora (p = 0.023), and more likely to have a positive regurgitation on pressure over the lacrimal sac (ROPLAS) sign (p = 0.003). Multifactorial analysis showed that older age, positive ROPLAS and hypertension were significant independent predictors of DE (p < 0.05). Among the 147 unilateral PANDO patients without DE, the TMH, NIKBUT-first, NIKBUT-average and bulbar erythema scores were significantly higher in the PANDO sides.
    CONCLUSIONS: This study illustrated the prevalence of DE in PANDO patients was 29.1% and DE is more likely to occur in those who are older, have hypertension and are positive for ROPLAS. In addition, in patients with unilateral nasolacrimal duct obstruction, a decrease in tear film stability was observed in the healthy eye.
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  • 文章类型: Journal Article
    目的:这项研究对超声弹性成像(USE)检测患有原发性干燥综合征(pSS)的个体的泪腺受累的有效性进行了全面评估。
    方法:对包括PubMed在内的多个数据库进行了全面搜索,Cochrane图书馆,EMBASE,万方,WebofScience,和中国国家知识基础设施,收集2000年1月1日至2023年10月1日在诊断PSS中应用USE的相关文献。汇总数据用于计算灵敏度,特异性,和诊断赔率比。使用了几个汇总指标来评估SWE在检测PSS方面的表现,包括接收器工作特性曲线下的面积,诊断赔率比,敏感性,和特殊性。
    结果:五项相关研究共包括273名患者。剪切波弹性成像(SWE)显示出0.88的合并敏感性(95%CI0.77-0.94)和0.94(95%CI0.88-0.98)的特异性,受试者工作特征曲线下面积为0.97(95%CI0.95-0.98)。SWE的阳性似然比为15.86(95%CI6.99-36.00),阴性似然比为0.13(95%CI0.07-0.25)。未观察到发表偏倚的证据(p=0.70)。
    结论:SWE在检测患有pSS的个体的泪腺受累方面具有显著的精确度。
    OBJECTIVE: This research conducted a comprehensive evaluation of the effectiveness of ultrasonic elastography (USE) in detecting lacrimal gland involvement in individuals suffering from primary Sjögren\'s syndrome (pSS).
    METHODS: A comprehensive search was undertaken across multiple databases including PubMed, the Cochrane Library, EMBASE, Wanfang, Web of Science, and the Chinese National Knowledge Infrastructure, to gather relevant literature pertaining to the application of USE in diagnosing pSS from January 1, 2000, to October 1, 2023. Pooled data were used to calculate sensitivity, specificity, and diagnostic odds ratios. Several summary metrics were used to evaluate SWE\'s performance in detecting pSS, including the area under the receiver operating characteristic curve, diagnostic odds ratios, sensitivities, and specificities.
    RESULTS: Five pertinent studies included a total of 273 patients. Shear wave elastography (SWE) demonstrated a pooled sensitivity of 0.88 (95% CI 0.77-0.94) and specificity of 0.94 (95% CI 0.88-0.98), with an area under the receiver operating characteristic curve of 0.97 (95% CI 0.95-0.98). SWE exhibited a positive likelihood ratio of 15.86 (95% CI 6.99-36.00) and a negative likelihood ratio of 0.13 (95% CI 0.07-0.25). No evidence of publication bias was observed (p = 0.70).
    CONCLUSIONS: SWE demonstrates a remarkable degree of precision in detecting lacrimal gland involvement in individuals suffering from pSS.
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  • 文章类型: Journal Article
    原发性干燥综合征(pSS)是一种全身性自身免疫性疾病,会影响体内的各个系统,导致眼睛和口腔干涩等症状,疼痛,和疲劳。炎症在pSS及其相关并发症中起关键作用,慢性炎症在pSS患者中很常见。这篇文献综述强调了可以作为预测pSS疾病进展的指标的炎症标志物。pSS患者的实验室标志物频繁且显著增加,包括红细胞沉降率,C反应蛋白,补体蛋白,S100蛋白,细胞因子(IFNs,CD40配体,可溶性CD25,类风湿因子,白细胞介素,和TNF-α),和趋化因子(CXCL13、CXCL10、CCL2、CXCL11和CCL25)。这些炎性标志物可用作pSS中疾病进展的预后指标。总之,本综述中报道的研究结果表明,高水平的炎症标志物可能作为pSS疾病进展的标志物,which,反过来,可能是有价值的预测疾病的结果。
    Primary Sjögren syndrome (pSS) is a systemic autoimmune disorder that affects various systems in the body, resulting in symptoms such as dry eyes and mouth, pain, and fatigue. Inflammation plays a critical role in pSS and its associated complications, with chronic inflammation being a common occurrence in patients with pSS. This review of the literature highlights inflammatory markers that could serve as indicators to predict disease progression in pSS. Laboratory markers are frequently and significantly increased in pSS patients, including erythrocyte sedimentation rate, C-reactive protein, complement proteins, S100 proteins, cytokines (IFNs, CD40 ligand, soluble CD25, rheumatoid factors, interleukins, and TNF-α), and chemokines (CXCL13, CXCL10, CCL2, CXCL11, and CCL25). These inflammatory markers can be used as prognostic indicators for disease progression in pSS. In conclusion, the results from the studies reported in this review indicate that high levels of inflammatory markers may serve as markers for disease progression of pSS, which, in turn, may be valuable in predicting disease outcome.
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  • 文章类型: Journal Article
    目的:I-131治疗后与分化型甲状腺癌(DTC)相关的最常见的泪器功能障碍是干眼和鼻泪管阻塞(NLDO),导致患者眼部不适和生活质量下降。诊断和管理与I-131治疗DTC相关的泪器功能障碍至关重要。因此,本文旨在全面总结和分析I-131治疗DTC导致泪器功能障碍的机制和治疗方案的进展。
    方法:CNKI综合检索,PubMed,和WedofScience从数据库中进行到2023年12月。关键搜索词是\"甲状腺癌\",\"I-131\",“并发症”,\"干眼\",\"Epiphora\",\"眼泪\",“鼻泪管”和“NLDO”。
    结果:研究表明,I-131治疗DTC会对泪腺和鼻泪管系统造成损害,导致干眼症等症状,顿唇,还有粘液分泌物.此外,最近的研究集中在探索疾病的相关危险因素以及实验和临床治疗。然而,关于所涉及的机制存在一些争议,无论是由于I-131在眼泪中的被动流动,泪囊和鼻泪管中的钠碘转运体(NIS)主动摄取I-131,或由I-131引起的继发性代谢和激素紊乱。
    结论:眼科医生的早期发现和预防措施至关重要,并且需要进一步研究以阐明该疾病的潜在机制。
    OBJECTIVE: The most prevalent lacrimal apparatus dysfunctions associated with differentiated thyroid cancer(DTC) after I-131 therapy are dry eye and nasolacrimal duct obstruction(NLDO), leading to ocular discomfort and lower quality of life for patients. It is crucial to diagnose and manage lacrimal apparatus dysfunction associated with I-131 therapy for DTC. Therefore, this review aims to comprehensively summarize and analyze the advances in mechanisms and therapeutic options underlying lacrimal apparatus dysfunction induced by I-131 therapy for DTC.
    METHODS: A comprehensive search of CNKI, PubMed, and Wed of Science was performed from the database to December of 2023. Key search terms were \"Thyroid cancer\", \"I-131\", \"Complications\", \"Dry eye\", \"Epiphora\", \"Tear\", \"Nasolacrimal duct\" and \"NLDO\".
    RESULTS: The research indicates that I-131 therapy for DTC causes damage to the lacrimal glands and nasolacrimal duct system, resulting in symptoms such as dry eye, epiphora, and mucoid secretions. Moreover, recent research has focused on exploring relevant risk factors of the condition and experimental and clinical treatments. However, there is some controversy regarding the mechanisms involved, whether it is due to the passive flow of I-131 in tears, active uptake of I-131 by the sodium-iodide symporter (NIS) in the lacrimal sac and nasolacrimal duct, or secondary metabolic and hormonal disturbances caused by I-131.
    CONCLUSIONS: It is crucial for early detection and preventive measures by ophthalmologists and the need for further studies to elucidate the mechanisms underlying the disease.
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  • 文章类型: Journal Article
    本研究旨在使用针对干眼症的虚拟设置问卷评估OSDI-6(C-OSDI-6)的中文翻译版本的有效性。共有270名参与者(136名男性,50.4%和134名女性,49.6%),评估平均年龄28.22±9.01岁,根据干眼研讨会提出的标准诊断完成了OSDI-12问卷的中文翻译版本(C-OSDI-12)。使用选定项目的研究数据(一种称为虚拟验证的新方法)分析了有效性和心理测量特性。根据OSDI-6的作者的建议,从C-OSDI-12中提取了六个项目,并进行了比较。C-OSDI-12和C-OSDI-6的总分分别为30.27±13.19和6.95±3.53。在总C-OSDI-6评分和总C-OSDI-12评分之间发现显著的可靠性(r=0.865,p<0.001)。C-OSDI-6的感染和装备在1.26和0.78之间。在中国成人干眼参与者中,C-OSDI-6证明有效且具有心理测量反应。这项虚拟验证研究的结果需要在实际使用的纵向验证研究中得到证实。
    This study aimed to evaluate the validity of the Chinese translation version of OSDI-6 (C-OSDI-6) using a virtual set-up questionnaire for dry eye disease. A total of 270 participants (136 males, 50.4% and 134 females, 49.6%) with a mean age of 28.22 ± 9.01 years were assessed, diagnosed under the criteria put forth by Dry Eye Workshop completed the Chinese translated version of the OSDI-12 questionnaire (C-OSDI-12). Validity and psychometric properties were analyzed using the study data on the selected items (a new approach called virtual validation). The six items were extracted from the C-OSDI-12 as suggested by the authors of OSDI-6 and compared. The total scores of C-OSDI-12 and C-OSDI-6 were 30.27 ± 13.19 and 6.95 ± 3.53, respectively. Significant reliability was found between the total C-OSDI-6 score and the total C-OSDI-12 score (r = 0.865, p < 0.001). Infits and outfits of the C-OSDI-6 were between 1.26 and 0.78.The C-OSDI-6 proved valid and psychometrically responsive in Chinese adult dry eye participants. The findings of this virtual validation study need to be confirmed in a longitudinal validation study on real-world use.
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  • 文章类型: Journal Article
    背景:干眼症是一种由泪膜不稳定或眼表微环境失衡引起的慢性多因素眼表疾病。它可能导致各种不适,例如眼表炎症和视觉问题。然而,干眼症的发病机制尚不清楚,这导致干眼症在临床实践中只能缓解但不能治愈。寻找干眼症的多种环境通路,探索干眼症的发病机制已成为研究的热点。研究发现,微生物群的变化可能与干眼病的发生、发展有关。
    方法:输入关键字\"干眼\",\"微生物群\",“细菌”通过pubmed,总结了符合纳入标准的文章,然后在过去5年中定义了文献的发表时间范围的同时对其进行过滤,截止日期为2023年。共筛选出13篇临床和1篇动物相关研究文章,纳入总结。
    结果:研究发现,细菌的不同成分可以通过存在于眼表的不同受体诱导眼部免疫反应,从而导致眼表微环境的不平衡。当干眼综合征发生时,还发现眼表微生物群和肠道微生物群的变化,包括多样性的变化,促炎细菌的增加,以及产生抗炎作用的短链脂肪酸相关细菌属的减少。粪便微生物移植或益生菌干预可减轻干眼动物模型眼表的炎症体征。
    结论:通过总结干眼发生时眼表和肠道菌群的变化,推测并得出结论,肠道可能通过多种途径和机制影响干眼症等眼部疾病的发生,例如异常免疫反应的发生,微生物群代谢-短链脂肪酸的干预,促炎和抗炎因子失衡,和神经递质的释放,等。从微生物群角度分析肠道与眼睛的相关性,可为今后多方位缓解干眼症提供理论依据和新思路。
    BACKGROUND: Dry eye is a chronic and multifactorial ocular surface disease caused by tear film instability or imbalance in the microenvironment of the ocular surface. It can lead to various discomforts such as inflammation of the ocular surface and visual issues. However, the mechanism of dry eye is not clear, which results in dry eye being only relieved but not cured in clinical practice. Finding multiple environmental pathways for dry eye and exploring the pathogenesis of dry eye have become the focus of research. Studies have found that changes in microbiota may be related to the occurrence and development of dry eye disease.
    METHODS: Entered the keywords \"Dry eye\", \"Microbiota\", \"Bacteria\" through PUBMED, summarised the articles that meet the inclusion criteria and then filtered them while the publication time range of the literature was defined in the past 5 years, with a deadline of 2023.A total of 13 clinical and 1 animal-related research articles were screened out and included in the summary.
    RESULTS: Study found that different components of bacteria can induce ocular immune responses through different receptors present on the ocular surface, thereby leading to an imbalance in the ocular surface microenvironment. Changes in the ocular surface microbiota and gut microbiota were also found when dry eye syndrome occurs, including changes in diversity, an increase in pro-inflammatory bacteria, and a decrease in short-chain fatty acid-related bacterial genera that produce anti-inflammatory effects. Fecal microbiota transplantation or probiotic intervention can alleviate signs of inflammation on the ocular surface of dry eye animal models.
    CONCLUSIONS: By summarizing the changes in the ocular surface and intestinal microbiota when dry eye occurs, it is speculated and concluded that the intestine may affect the occurrence of eye diseases such as dry eye through several pathways and mechanisms, such as the occurrence of abnormal immune responses, microbiota metabolites- intervention of short-chain fatty acids, imbalance of pro-inflammatory and anti-inflammatory factors, and release of neurotransmitters, etc. Analyzing the correlation between the intestinal tract and the eyes from the perspective of microbiota can provide a theoretical basis and a new idea for relieving dry eyes in multiple ways in the future.
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  • 文章类型: Journal Article
    本研究采用CiteSpace软件对研究现状进行分析,热点,和原发性干燥综合征(pSS)的趋势。1999年至2023年的相关出版物在WebofScienceCoreCollection(WoSCC)集中进行了搜索,然后使用CiteSpace软件生成网络图以确定顶级作者,机构,国家,关键词,期刊,参考文献,和研究趋势。本研究共纳入3564篇有效文章。中华人民共和国的文章数量最多(n=524),而卑尔根大学成为出版物数量最高的机构(n=94)。MarietteX被确定为出版物最多的作者(n=67),而VitaliC被认可为被引用最多的作者(n=1706)。风湿病年鉴是引文计数最高的期刊(n=2530)。值得注意的是,2017年发表在《风湿病年鉴》上的一篇文章因被引用了304次而引起了极大的关注。文献计量分析显示,pSS研究的关键领域包括研究发病机理;推进和应用靶向生物制剂;建立治疗和诊断标准。
    This study employs CiteSpace software to analyze the research status, hotspots, and trends of primary Sjogren syndrome (pSS). Relevant publications from 1999 to 2023 were searched in the Web of Science Core Collection (WoSCC) set, followed by generating a network map using CiteSpace software to identify top authors, institutions, countries, keywords, journals, references, and research trends. A total of 3564 valid articles were included in this study. The People Republic of China had the highest number of articles (n = 524), while the University of Bergen emerged as the institution with the highest publication count (n = 94). Mariette X was identified as the author with the most publications (n = 67), whereas Vitali C received recognition as the most cited author (n = 1706). Annals of Rheumatic Diseases stood out as the journal with the highest citation count (n = 2530). Notably, an article published in the Annals of Rheumatic Diseases in 2017 garnered significant attention by being cited a remarkable 304 times. The bibliometric analysis reveals that key areas of research in pSS encompass investigating pathogenesis; advancing and applying targeted biological agents; and establishing treatment and diagnostic standards.
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  • 文章类型: Case Reports
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