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Clozapine Augmentation with Antipsychotics among Patients with Schizophrenia Spectrum Disorders in the Ontario Forensic Psychiatry System 安大略省法医精神病学系统中精神分裂症谱系障碍患者的氯氮平增强抗精神病药物
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-03 DOI: 10.1016/j.arcmed.2025.103365
Mark Mohan Kaggwa , Joan Abaatyo , Tolulope Oladimeji , Precious Agboinghale , John MW Bradford , Gary Andrew Chaimowitz , Andrew Toyin Olagunju

Background

Clozapine augmentation with antipsychotics (CAA) is commonly used to treat complex cases in forensic psychiatric settings. This study aims to investigate the prevalence and determinants of CAA among individuals with schizophrenia spectrum disorders within the Ontario forensic system.

Methods

A retrospective analysis was conducted on 262 patients in forensic psychiatric settings who were prescribed clozapine during the 2014/15 reporting year. The mean age of the patients was 41 years (SD = 11.8), and 227 of them (86.6%) were male. For comparative analysis, the patients were categorized into two groups: clozapine monotherapy and CAA. Logistic regression analysis was then applied to evaluate factors associated with CAA.

Results

Nearly half (48.5%) of forensic psychiatric patients on clozapine received antipsychotic augmentation. CAA was more prevalent among patients with violent offenses (adjusted odds ratio [aOR] 4.32, 95% confidence interval [CI]: 1.02–18.27, p = 0.047), and absconsion incidents (aOR 2.55 95% CI: 1.16–5.58, p = 0.019). Patients with a good treatment response (aOR of 0.25, 95% CI: 0.11–0.54, p <0.001) and a history of self-harm were less likely to be prescribed CAA (aOR of 0.32, 95% CI: 0.12–0.85, p = 0.022).

Conclusion

Patients with severe symptoms and significant risk profiles were more likely to receive CAA. Capacity development and further research are needed to support an effective and safe clozapine therapy strategy.
背景:氯氮平增强抗精神病药物(CAA)通常用于治疗法医精神病学设置的复杂病例。本研究旨在调查CAA在安大略省法医系统中精神分裂症谱系障碍患者中的患病率和决定因素。方法:对2014/15报告年度法医精神科使用氯氮平的262例患者进行回顾性分析。患者平均年龄41岁(SD = 11.8),男性227例(86.6%)。为了比较分析,将患者分为氯氮平单药组和CAA组。然后应用Logistic回归分析评价与CAA相关的因素。结果:近一半(48.5%)使用氯氮平的法医精神病患者接受了抗精神病药物增强治疗。CAA在暴力犯罪(调整比值比[aOR] 4.32, 95%可信区间[CI]: 1.02 ~ 18.27, p = 0.047)和吸走(aOR: 2.55, 95% CI: 1.16 ~ 5.58, p = 0.019)患者中更为普遍。治疗反应良好的患者(aOR为0.25,95% CI: 0.11-0.54, p)结论:症状严重且风险特征显著的患者更有可能接受CAA。需要能力发展和进一步的研究来支持有效和安全的氯氮平治疗策略。
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引用次数: 0
Epidemiologic Characterization and Risk Factors of Rocky Mountain Spotted Fever in Children in Northeastern Mexico: A Retrospective Cross-sectional Study (2018–2024) 墨西哥东北部儿童落基山斑疹热流行病学特征及危险因素:回顾性横断面研究(2018-2024)
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-03 DOI: 10.1016/j.arcmed.2025.103367
José Iván Castillo Bejarano , Érika Aidé Larragoity González , Susana Patricia Cantú González , Abiel Homero Mascareñas de los Santos , Rodrigo García Pérez , Sara Paulina Rosales-González , Diego Armando Alvarado Lara , María Fernanda Cid Ramírez , Alfredo Castillo Mariscal , Denisse Natalie Vaquera Aparicio

Background

Rocky Mountain spotted fever (RMSF) is a vector-borne disease with nonspecific symptoms, including fever, headache, myalgia, and exanthema, which complicates timely diagnosis and treatment. Despite its significant morbidity and mortality, epidemiological data and risk factor analyses remain scarce in Mexico.

Methods

A retrospective cross-sectional study was conducted from 2018–2024 in three hospitals in northeastern Mexico. We analyzed 90 pediatric patients with confirmed rickettsiosis via polymerase chain reaction (PCR) or immunofluorescence assay (IFA). Demographic, clinical, and laboratory data were evaluated to identify independent risk factors associated with disease severity and outcomes. Statistical analyses included logistic regression, Mann-Whitney U tests, and Pearson χ2 tests (p ≤0.05).

Results

School-aged children comprised 46.6% of cases, with a predominance of females (54.4%). Key epidemiological exposures included tick bites (17.8%) and pet cohabitation (54.5%). Delayed doxycycline treatment (>5 d after symptom onset) was associated with increased mortality. Significant predictors of poor outcomes were neurological impairment (OR: 3.7, CI: 1.9–7.3), shock upon admission (OR: 4.5, CI: 2.2–9.1), and thrombocytopenia (p < 0.001). The overall mortality rate was 36.7%.

Conclusions

Our findings underscore the significant clinical impact of rickettsioses in northeastern Mexico and the need to improve diagnostic capabilities, raising public awareness, and implementing effective vector control programs. Early recognition and timely doxycycline treatment are crucial to improving patient outcomes. Strengthening public health strategies through preventive measures and clinician education could reduce the morbidity and mortality associated with these infections.
背景:落基山斑疹热(RMSF)是一种媒介传播的疾病,具有非特异性症状,包括发烧、头痛、肌痛和皮疹,难以及时诊断和治疗。尽管墨西哥的发病率和死亡率很高,但流行病学数据和风险因素分析仍然很少。方法:2018-2024年在墨西哥东北部三家医院进行回顾性横断面研究。我们通过聚合酶链反应(PCR)或免疫荧光法(IFA)分析了90例确诊立克次体病的儿童患者。对人口统计学、临床和实验室数据进行评估,以确定与疾病严重程度和结局相关的独立危险因素。统计学分析采用logistic回归、Mann-Whitney U检验和Pearson χ2检验(p≤0.05)。结果:学龄儿童占46.6%,以女性为主(54.4%)。主要流行病学暴露为蜱叮咬(17.8%)和宠物同居(54.5%)。延迟强力霉素治疗(症状出现后5天)与死亡率增加相关。不良预后的重要预测因子是神经功能障碍(OR: 3.7, CI: 1.9-7.3)、入院时休克(OR: 4.5, CI: 2.2-9.1)和血小板减少(p < 0.001)。总死亡率为36.7%。结论:我们的研究结果强调了墨西哥东北部立克次体病的重要临床影响,以及提高诊断能力、提高公众意识和实施有效媒介控制计划的必要性。早期识别和及时的强力霉素治疗对改善患者预后至关重要。通过预防措施和临床医生教育加强公共卫生战略可以降低与这些感染有关的发病率和死亡率。
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引用次数: 0
Long-term Outcomes of Psoriatic Arthritis in Daily Practice: Results from a Real World Cohort 日常实践中银屑病关节炎的长期预后:来自真实世界队列的结果
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-03 DOI: 10.1016/j.arcmed.2025.103363
Alireza Khabbazi , Amir Jamshidi , Nasrin Moghimi , Kamal Esalatmanesh , Zahra Mirfeizi , Mehrzad Hajialilo , Mehdi Jafarpour , Omid Rahbar Farzam , Maryam Saberivand , Aida Malek Mahdavi

Aim

This study aimed to investigate the outcomes of psoriatic arthritis (PsA) and its influencing factors in real-world practice.

Methods

In the current multicenter study, 321 patients with PsA aged >18 years, being followed-up for at least six months, and visited at least three times per year, were collected from four referral rheumatology centers. Disease outcomes were evaluated with rate of minimal disease activity (MDA), sustained remission, medication-free remission, and occurrence of clinically damaged joints from the time of diagnosis to the last visit.

Results

Mean age at diagnosis was 41.7 years and median follow-up duration was 36 months. MDA and sustained remission occurred at least once in 228 and 74 patients. Medication-free remission occurred in 34 (10.7%) patients. At least one clinically damaged joint was present in 99 (30.8%) patients at the last visit. Current smoking and psoriasis phenotype of skin psoriasis were predictors of sustained remission. Having no flare after sustained remission and PsA before or concurrently with psoriasis were predictors of medication-free remission. Age at cohort entry over 40, starting PsA after psoriasis, and going to sustained remission over six months of treatment were predictors of having clinically damaged joints.

Conclusion

A significant proportion of patients with PsA achieved sustained remission in daily practice; however, medication-free remission remained unachievable.
目的探讨银屑病关节炎(PsA)的临床疗效及其影响因素。方法在当前的多中心研究中,从四个转诊风湿病中心收集了321例年龄为18岁的PsA患者,随访至少6个月,每年至少访问3次。通过最小疾病活动率(MDA)、持续缓解、无药物缓解和从诊断到最后一次就诊的临床关节损伤发生率来评估疾病结局。结果确诊时平均年龄41.7岁,中位随访时间36个月。MDA和持续缓解至少在228例和74例患者中出现一次。34例(10.7%)患者出现无药物缓解。最后一次访问时,99例(30.8%)患者至少存在一个临床关节损伤。当前吸烟和牛皮癣表型是牛皮癣持续缓解的预测因子。持续缓解后无耀斑和牛皮癣前或并发的PsA是无药物缓解的预测因子。队列入组时年龄超过40岁,牛皮癣后开始PsA治疗,治疗6个月后持续缓解是临床关节损伤的预测因素。结论PsA患者在日常实践中有显著比例实现持续缓解;然而,无药物缓解仍然无法实现。
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引用次数: 0
Reviewers list 评论家列表
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-01 DOI: 10.1016/S0188-4409(25)00189-4
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引用次数: 0
Comparative Analysis of Adipose Tissue Depots in Immediate versus Delayed Breast Reconstruction 即时与延迟乳房重建脂肪组织库的比较分析。
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-23 DOI: 10.1016/j.arcmed.2025.103360
Carlos Pinho , Beatriz Soares , Beatriz Costa , Diogo Teixeira , Maria J. Salazar , Fani L. Neto , Henrique Almeida , António Costa-Ferreira , Adriana R. Rodrigues , Alexandra M. Gouveia

Background

Mastectomy followed by breast reconstruction is the standard treatment for breast cancer. Choosing autologous tissue requires an in-depth understanding of the molecular and structural characteristics of the different adipose tissue depots.

Method

White adipose tissue (WAT) from five different locations (above and below the abdominal Scarpa’s fascia, thighs, breast skin envelope, and omentum) was collected from 24 patients undergoing breast reconstruction and grouped based on immediate (IBR) or delayed (DBR) reconstruction. The adipocyte area was analyzed in histologically processed WAT sections. Transcription and protein expression profiles, related to inflammation, fibrosis, browning, and adipose-derived stem cells (ADSCs) content were determined by RT-qPCR and Western blotting.

Results

Compared to IBR, omental WAT from DBR patients exhibits larger adipocytes, and higher expression of TIMP1, FN1, CD206, and CD45, as well as lower levels of CIDEA. Breast fat also differs between the two groups, with lower levels of IL6 and CIDEA, and overexpression of FN1 in the DBR group. Within the IBR group, breast fat shows higher levels of IL6, TIMP1 and CIDEA, but lower expression of FN1 and COL3A1 than subcutaneous WAT.

Conclusion

Omental fat in the IBR cohort has properties similar to those of subcutaneous WAT, indicating that the omentum is a promising candidate for rapid breast restoration. In the DBR group, the omentum molecular signature suggests a change towards a pro-fibrotic phenotype and a reduced remodeling capacity, suggesting that it should not be the primary choice for breast reconstruction. This study emphasizes the importance of careful WAT selection to minimize adverse outcomes, including cancer recurrence, and underscores the diverse physiology of fat depots.
背景:乳房切除术后乳房重建是乳腺癌的标准治疗方法。选择自体组织需要深入了解不同脂肪组织库的分子和结构特征。方法:选取24例乳房再造术患者的5个不同部位(腹部斯卡帕筋膜上下、大腿、乳房皮肤包膜、大网膜)的白色脂肪组织(WAT),按即刻(IBR)或延迟(DBR)再造术分组。在组织学处理的WAT切片上分析脂肪细胞面积。通过RT-qPCR和Western blotting检测与炎症、纤维化、褐变和脂肪源性干细胞(ADSCs)含量相关的转录和蛋白质表达谱。结果:与IBR相比,DBR患者网膜WAT表现出更大的脂肪细胞,TIMP1、FN1、CD206和CD45的表达更高,而CIDEA的表达水平更低。两组之间的乳腺脂肪也不同,DBR组的il - 6和CIDEA水平较低,FN1过表达。与皮下WAT相比,IBR组乳腺脂肪中IL6、TIMP1和CIDEA水平较高,而FN1和COL3A1表达较低。结论:IBR患者的大网膜脂肪具有与皮下WAT相似的特性,表明大网膜是快速乳房修复的有希望的候选者。在DBR组中,大网膜分子特征提示促纤维化表型的改变和重塑能力的降低,这表明它不应该是乳房重建的首选。本研究强调了谨慎选择WAT以减少不良后果(包括癌症复发)的重要性,并强调了脂肪库的多种生理特征。
{"title":"Comparative Analysis of Adipose Tissue Depots in Immediate versus Delayed Breast Reconstruction","authors":"Carlos Pinho ,&nbsp;Beatriz Soares ,&nbsp;Beatriz Costa ,&nbsp;Diogo Teixeira ,&nbsp;Maria J. Salazar ,&nbsp;Fani L. Neto ,&nbsp;Henrique Almeida ,&nbsp;António Costa-Ferreira ,&nbsp;Adriana R. Rodrigues ,&nbsp;Alexandra M. Gouveia","doi":"10.1016/j.arcmed.2025.103360","DOIUrl":"10.1016/j.arcmed.2025.103360","url":null,"abstract":"<div><h3>Background</h3><div>Mastectomy followed by breast reconstruction is the standard treatment for breast cancer. Choosing autologous tissue requires an in-depth understanding of the molecular and structural characteristics of the different adipose tissue depots.</div></div><div><h3>Method</h3><div>White adipose tissue (WAT) from five different locations (above and below the abdominal Scarpa’s fascia, thighs, breast skin envelope, and omentum) was collected from 24 patients undergoing breast reconstruction and grouped based on immediate (IBR) or delayed (DBR) reconstruction. The adipocyte area was analyzed in histologically processed WAT sections. Transcription and protein expression profiles, related to inflammation, fibrosis, browning, and adipose-derived stem cells (ADSCs) content were determined by RT-qPCR and Western blotting.</div></div><div><h3>Results</h3><div>Compared to IBR, omental WAT from DBR patients exhibits larger adipocytes, and higher expression of <em>TIMP1, FN1, CD206</em>, and <em>CD45</em>, as well as lower levels of <em>CIDEA</em>. Breast fat also differs between the two groups, with lower levels of <em>IL6</em> and <em>CIDEA,</em> and overexpression of <em>FN1</em> in the DBR group. Within the IBR group, breast fat shows higher levels of <em>IL6, TIMP1</em> and <em>CIDEA</em>, but lower expression of <em>FN1</em> and <em>COL3A1</em> than subcutaneous WAT.</div></div><div><h3>Conclusion</h3><div>Omental fat in the IBR cohort has properties similar to those of subcutaneous WAT, indicating that the omentum is a promising candidate for rapid breast restoration. In the DBR group, the omentum molecular signature suggests a change towards a pro-fibrotic phenotype and a reduced remodeling capacity, suggesting that it should not be the primary choice for breast reconstruction. This study emphasizes the importance of careful WAT selection to minimize adverse outcomes, including cancer recurrence, and underscores the diverse physiology of fat depots.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"57 1","pages":"Article 103360"},"PeriodicalIF":3.4,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sex Specific Threshold Effects of Prenatal Stress on Striatal Microglia and Relevant Behaviors in Mice 性别特异性阈值对小鼠纹状体小胶质细胞的影响及相关行为
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-20 DOI: 10.1016/j.arcmed.2025.103364
Sara V. Maurer , Maya M. Evans , Mia Dukle , Sreelekha Kundu , Jessica L. Dennis , Rhett M. Ellerbroek , Samantha L. Anema , Venezia C. Roshko , Hanna E. Stevens

Background

Prenatal stress, a neurodevelopmental disorder (NDD) risk factor, induces neurobehavioral alterations, including offspring neuroimmune cells. Variable offspring outcomes may arise from the extent to which prenatal stress crosses “thresholds” for specific effects. Therefore, we sought to determine offspring outcomes using models with different extents of prenatal stress. We focused on striatal outcomes, because of their relevance for NDDs.

Methods

Pregnant CD1 mice were assigned to four groups (each: n = 6): no stress (“NoS”) or stressors administered three times daily: i.p. saline injections (low prenatal stress, LoS), interleukin-6 injections as a component of prenatal stress (immune prenatal stress; ImS), or restraint stress + saline injections (high prenatal stress, HiS), embryonic days 12–18. Behavioral (open field, rotarod, amphetamine-induced stereotypy, water T-maze) and brain and placental immunohistochemical (Iba1, Ki67) assessments of offspring were performed.

Results

In adult offspring, HiS altered behaviors across males and females, while ImS induced fewer behavioral changes, and LoS did not affect behavior. Adult striatal microglia morphologies were mostly unchanged across groups, with only HiS altering striatal density of minimally-ramified cells. However, embryonic striatal microglia were affected by all stressors in distinct ways. The HiS model, and to a lesser extent LoS, also influenced immune components of the maternal-fetal interface: placental macrophages.

Conclusions

High and immune stress affected adult striatal-dependent behavior, exceeding the threshold necessary for persistent impacts mostly in males, but all stress models affected embryonic microglia, suggesting a lower threshold for early neuroimmune impacts. Distinct severities and aspects of prenatal stress may therefore underlie different NDD-relevant outcomes.
产前应激是一种神经发育障碍(NDD)的危险因素,可诱导神经行为改变,包括后代的神经免疫细胞。由于产前压力在多大程度上超过了特定影响的“阈值”,可能会产生不同的后代结果。因此,我们试图用不同程度的产前应激模型来确定后代的结局。我们关注纹状体结果,因为它们与ndd相关。方法将妊娠CD1小鼠分为4组(每组n = 6):无应激组(NoS)或应激源组(每日3次):在胚胎期12-18天内进行生理盐水注射(低产前应激,LoS)、白细胞介素-6注射作为产前应激的组成部分(免疫产前应激,ImS)或约束应激+生理盐水注射(高产前应激,HiS)。对子代进行行为学(开放场地,旋转杆,安非他明诱导的刻板印象,水t迷宫)和脑和胎盘免疫组织化学(Iba1, Ki67)评估。结果在成年后代中,他改变了雄性和雌性的行为,而im引起的行为改变较少,LoS对行为没有影响。各组成体纹状体小胶质细胞形态基本不变,只有最小分枝细胞的纹状体密度发生改变。然而,所有应激源对胚胎纹状体小胶质细胞的影响各不相同。HiS模型和LoS在较小程度上也影响母胎界面的免疫成分:胎盘巨噬细胞。结论高应激和免疫应激影响成年纹状体依赖行为,主要在雄性中超过持续影响所需的阈值,但所有应激模型都影响胚胎小胶质细胞,提示早期神经免疫影响的阈值较低。因此,产前压力的不同严重程度和方面可能是ndd相关结果不同的基础。
{"title":"Sex Specific Threshold Effects of Prenatal Stress on Striatal Microglia and Relevant Behaviors in Mice","authors":"Sara V. Maurer ,&nbsp;Maya M. Evans ,&nbsp;Mia Dukle ,&nbsp;Sreelekha Kundu ,&nbsp;Jessica L. Dennis ,&nbsp;Rhett M. Ellerbroek ,&nbsp;Samantha L. Anema ,&nbsp;Venezia C. Roshko ,&nbsp;Hanna E. Stevens","doi":"10.1016/j.arcmed.2025.103364","DOIUrl":"10.1016/j.arcmed.2025.103364","url":null,"abstract":"<div><h3>Background</h3><div>Prenatal stress, a neurodevelopmental disorder (NDD) risk factor, induces neurobehavioral alterations, including offspring neuroimmune cells. Variable offspring outcomes may arise from the extent to which prenatal stress crosses “thresholds” for specific effects. Therefore, we sought to determine offspring outcomes using models with different extents of prenatal stress. We focused on striatal outcomes, because of their relevance for NDDs.</div></div><div><h3>Methods</h3><div>Pregnant CD1 mice were assigned to four groups (each: n = 6): no stress (“NoS”) or stressors administered three times daily: i.p. saline injections (low prenatal stress, LoS), interleukin-6 injections as a component of prenatal stress (immune prenatal stress; ImS), or restraint stress + saline injections (high prenatal stress, HiS), embryonic days 12–18. Behavioral (open field, rotarod, amphetamine-induced stereotypy, water T-maze) and brain and placental immunohistochemical (Iba1, Ki67) assessments of offspring were performed.</div></div><div><h3>Results</h3><div>In adult offspring, HiS altered behaviors across males and females, while ImS induced fewer behavioral changes, and LoS did not affect behavior. Adult striatal microglia morphologies were mostly unchanged across groups, with only HiS altering striatal density of minimally-ramified cells. However, embryonic striatal microglia were affected by all stressors in distinct ways. The HiS model, and to a lesser extent LoS, also influenced immune components of the maternal-fetal interface: placental macrophages.</div></div><div><h3>Conclusions</h3><div>High and immune stress affected adult striatal-dependent behavior, exceeding the threshold necessary for persistent impacts mostly in males, but all stress models affected embryonic microglia, suggesting a lower threshold for early neuroimmune impacts. Distinct severities and aspects of prenatal stress may therefore underlie different NDD-relevant outcomes.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"57 1","pages":"Article 103364"},"PeriodicalIF":3.4,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Being the Chief Editor of a Scientific Journal 成为科学期刊的主编
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-20 DOI: 10.1016/j.arcmed.2025.103370
Mardia López-Alarcón
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引用次数: 0
Synovial Fluid Autoantibodies and Cytokines in Rheumatoid Arthritis Potential Biomarkers and Insight into Disease Pathogenesis 类风湿性关节炎滑膜液自身抗体和细胞因子的潜在生物标志物和疾病发病机制的见解
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-12 DOI: 10.1016/j.arcmed.2025.103329
Shiyao Wu , Li Wang , Honglin Zhu , Yanli Xie , Ying Jiang , Xiaoli Zhang , Yaou Zhou , Jiaomei Cheng , Quanzhen Li , Xiaoxia Zuo , Tong Li

Background

Rheumatoid arthritis (RA) is an autoimmune disease involving chronic synovitis and bone erosion. Most patients with RA have autoantibodies in their blood. However, the characteristics of autoantibodies and cytokines in RA synovial fluid (SF) are not fully understood.

Methods

SF samples were collected from 35 patients with RA and 10 with osteoarthritis (OA). Antigen microarrays were used to test for IgG and IgM antibodies, and Luminex was used to measure cytokines. Correlations between differentially expressed antibodies, cytokines, and clinical parameters were analyzed. KEGG and GO analysis were used to assess the genes of autoantibody targets and cytokines in RA SF.

Results

51 IgM autoantibodies, 25 IgG autoantibodies, and 43 cytokines were identified as differently expressed in RA SF compared to patients with OA. Correlation analysis revealed associations between IgM and IgG and several clinical and laboratory indicators. Newly identified antibodies in RA include anti-vitronectin, anti-glutathione S-transferase P1, and anti-calmodulin. We also identified a new cytokine, interferon α2, in RA SF. IgM autoantibodies correlated positively with basic fibroblast growth factors, IL-1α, IL-2, and IL-3. IgG autoantibodies correlated positively with IL-9 and IL-12. KEGG and GO analysis revealed that the differentially expressed autoantibody targets and cytokines were involved in the neutrophil extracellular trap (NET) formation and positively regulated NF-κB activity.

Conclusions

We identified three new autoantibodies and a new cytokine in RA SF. These findings, along with our enrichment analysis, suggest a potential role for NETs in the RA synovial microenvironment. This deepens our understanding of RA synovial microenvironment and identifies new approaches for innovative treatment strategies.
背景类风湿性关节炎(RA)是一种自身免疫性疾病,涉及慢性滑膜炎和骨侵蚀。大多数RA患者的血液中都有自身抗体。然而,RA滑液(SF)中自身抗体和细胞因子的特征尚不完全清楚。方法采集35例RA患者和10例OA患者的ssf样本。抗原微阵列检测IgG和IgM抗体,Luminex检测细胞因子。分析差异表达抗体、细胞因子和临床参数之间的相关性。采用KEGG和GO分析评估RA SF中自身抗体靶点和细胞因子的基因。结果51个IgM自身抗体、25个IgG自身抗体和43个细胞因子在RA SF中表达差异。相关分析显示IgM和IgG与一些临床和实验室指标之间存在相关性。新发现的RA抗体包括抗玻璃体粘连蛋白、抗谷胱甘肽s -转移酶P1和抗钙调蛋白。我们还在RA SF中发现了一种新的细胞因子,干扰素α2。IgM自身抗体与碱性成纤维细胞生长因子、IL-1α、IL-2和IL-3呈正相关。IgG自身抗体与IL-9、IL-12呈正相关。KEGG和GO分析显示,差异表达的自身抗体靶点和细胞因子参与中性粒细胞胞外陷阱(NET)的形成,并积极调节NF-κB活性。结论在RA SF中发现3个新的自身抗体和1个新的细胞因子。这些发现,以及我们的富集分析,表明NETs在RA滑膜微环境中的潜在作用。这加深了我们对RA滑膜微环境的理解,并确定了创新治疗策略的新方法。
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引用次数: 0
Diagnostic Evaluation of Seronegative Celiac Disease 血清阴性乳糜泻的诊断评价。
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-01 DOI: 10.1016/j.arcmed.2025.103338
Andrew Ford , Claire Jansson-Knodell , Alberto Rubio Tapia
Celiac disease (CeD) is an autoimmune condition that is traditionally characterized by the presence of serologic markers and flattening of the duodenal villi. However, a rare variant of the disease known as seronegative celiac disease (SNCeD), is characterized by an absence of these diagnostic serologies. The current diagnostic approach to this condition relies on excluding alternative seronegative enteropathies and confirming a positive CeD HLA genotype followed by an extended gluten-free diet (GFD). However, this current diagnostic approach is burdensome and underscores the need for more succinct methods. Encouragingly there are multiple tests that are being investigated for CeD diagnosis that also could extend to SNCeD diagnosis such as intestinal IgA anti-TG2 deposits, HLA-DQ tetramer assays, microRNA, interleukin-2, and flow cytometry among others.
乳糜泻(CeD)是一种自身免疫性疾病,传统上以血清学标志物和十二指肠绒毛变平为特征。然而,一种罕见的疾病变体,即血清阴性乳糜泻(SNCeD),其特征是缺乏这些诊断血清学。目前对这种疾病的诊断方法依赖于排除其他血清阴性肠病,并确认CeD HLA基因型阳性,然后延长无麸质饮食(GFD)。然而,目前的诊断方法是繁重的,并强调需要更简洁的方法。令人鼓舞的是,目前正在研究多种用于CeD诊断的检测方法,这些方法也可以扩展到SNCeD的诊断,如肠道IgA抗tg2沉积、HLA-DQ四聚体测定、microRNA、白细胞介素-2和流式细胞术等。
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引用次数: 0
Metabolic Dysfunction-Associated Steatohepatitis in Focus: Pathogenesis, Non-Invasive Diagnostics, and Future Approaches 代谢功能障碍相关脂肪性肝炎的焦点:发病机制,非侵入性诊断和未来的方法
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-01 DOI: 10.1016/j.arcmed.2025.103350
Abdulrahman Ismaiel , Mhd Bashir Almonajjed , Cristina Sorina Catana , Stefan-Lucian Popa , Dan L. Dumitrascu
Metabolic dysfunction-associated steatohepatitis (MASH) has become a critical public health concern, representing the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD). MASH is characterized by hepatic steatosis, inflammation, hepatocyte ballooning, and fibrosis, which increase the risk of cirrhosis and hepatocellular carcinoma. Closely linked to obesity, insulin resistance, and metabolic syndrome, MASH affects a significant proportion of the global population, requiring accurate diagnostic tools and tailored interventions. This manuscript delves into the current understanding of MASH, focusing on its pathophysiology, diagnostic challenges, and innovative non-invasive strategies. While liver biopsy remains the gold standard for diagnosis, its invasiveness and limitations have prompted the search for alternative approaches. Promising non-invasive techniques, such as elastography, MRI-based techniques, and serum biomarkers like cytokeratin-18, NIS4, and FAST scores, provide new ways to detect MASH and evaluate fibrosis severity. The updated MASLD criteria refine risk stratification further, capturing a broader range of at-risk individuals, including lean phenotypes. As MASH continues to strain healthcare systems worldwide, this review underscores the importance of advancing non-invasive diagnostics and integrating multi-omics approaches. Future research should focus on developing personalized strategies to halt disease progression, enhance early detection, and optimize patient outcomes.
代谢功能障碍相关脂肪性肝炎(MASH)已成为一个重要的公共卫生问题,代表了代谢功能障碍相关脂肪性肝病(MASLD)的进行性形式。MASH的特点是肝脂肪变性、炎症、肝细胞球囊化和纤维化,这些都增加了肝硬化和肝细胞癌的风险。MASH与肥胖、胰岛素抵抗和代谢综合征密切相关,影响着全球很大一部分人口,需要准确的诊断工具和量身定制的干预措施。这份手稿深入到目前对MASH的理解,侧重于其病理生理学,诊断挑战和创新的非侵入性策略。虽然肝活检仍然是诊断的金标准,但其侵入性和局限性促使人们寻找替代方法。有前途的非侵入性技术,如弹性成像、基于mri的技术和血清生物标志物,如细胞角蛋白-18、NIS4和FAST评分,提供了检测MASH和评估纤维化严重程度的新方法。更新的MASLD标准进一步细化了风险分层,捕获了更广泛的高危个体,包括瘦表型。随着MASH继续给全球医疗保健系统带来压力,本综述强调了推进非侵入性诊断和整合多组学方法的重要性。未来的研究应侧重于制定个性化的策略,以阻止疾病的进展,加强早期发现,并优化患者的预后。
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