Iodine 131 Treatment in Graves’ Disease in a West African Country: Preliminary Study about 25 Cases in Senegal

Introduction: Graves’ disease is the most common cause of hyperthyroidism. Its treatment uses synthetic antithyroid drugs but the use of aggressive radical therapy such as surgery or non-aggressive therapy such as iodine-131 is not uncommon. Treatment of Graves’ disease with radioactive iodine or iratherapy is a simple, inexpensive, well-tolerated treatment. It was introduced in Senegal in 2016. We report through this work the preliminary assessment of the only nuclear medicine service in Senegal in the management of Graves’ disease by iodine-131. Patients and Methods: Retrospective study of the first cases of Graves’ disease treated with iratherapy in Senegal. Socio-demographic, clinical, paraclinical, therapeutic and evolutionary aspects were studied. Radiation protection rules have been implemented and contraception has been effective for six months in women of childbearing age. Results: 25 patients were collected with a mean age of 45 years, twenty women (80%), a family goiter in 24% and a psycho-affective context in 64% of cases. Thyrotoxicosis syndrome was associated with goiter in 68% of patients and exophthalmos in 64%. Thyroid ultrasound performed in 20 patients showed vascular goiter in 80% and thyroid scintigraphy in 3 patients, homogeneous and diffuse hyperfixation. TRAK dosed in 8 patients was still positive. All patients had received first-line medical treatment. The average duration of this treatment was more than 18 months in 92%. The empirically used iodine-131 activity averaged 15.35 mCi. Oral corticosteroid therapy was prescribed in 7 patients for the prevention of malignant orbitopathy. No early side effects were noted. The remission rate at 3 months was 52% and at 6 months was 88% to 92%. Conclusion: The effectiveness of radioactive iodine, in particular ablative doses in the treatment of hyperthyroidism, is no longer to be demonstrated. Taking into account our socioeconomic context, iratherapy should be a treatment of choice for hyperthyroidism with a good quality/price ratio and excellent tolerance.

Comparative Analysis of Budesonide Treatments on Blood Gas and Inflammation in Chronic Obstructive Pulmonary Disease Remission

Objective:To investigate the effects of budesonide on blood gas and inflammation indexes in patients with chronic obstructive pulmonary disease(COPD)during remission.Methods:Fifty-one patients with COPD in remission,admitted to Zhongshan Hospital of Dalian University from July 2021 to December 2022,were selected and divided into two groups based on a randomized numerical table method.The control group(25 cases)received budesonide formoterol treatment,while the observation group(26 cases)received budesonide geforce treatment.Various indexes,including clinical efficacy,blood gas indexes,inflammation indexes,St.George’s Respiratory Questionnaire(SGRQ)scores,Chronic Obstructive Pulmonary Disease Assessment Test(CAT)scores,and 6-minute Walking Distance Test(6MWD)results,were compared between the two groups.Results:After 21 days of treatment,the total clinical effectiveness rate of the observation group was higher than that of the control group,with a statistically significant difference(P<0.05).Post-treatment,the PaO2 level and pH value in both groups were higher,and the PaCO_(2) level was lower compared to pre-treatment levels.The observation group showed better improvements in these indicators than the control group,with statistically significant differences(P<0.05).SGRQ and CAT scores for both groups were lower post-treatment,with the observation group scoring lower than the control group.Additionally,the 6MWD results were farther for both groups post-treatment,with the observation group achieving greater distances than the control group,with statistically significant differences(P<0.05).Conclusion:Budesonide can effectively improve blood gas indexes in patients with COPD in remission,alleviate related clinical symptoms,reduce inflammatory responses,and promote patient recovery.The treatment efficacy is significant.

Thyrotoxicosis in patients with a history of Graves'disease after SARS-CoV-2 vaccination(adenovirus vector vaccine):Two case reports

BACKGROUND Vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which were approved for emergency use have been administered on a large scale globally to contain the pandemic coronavirus disease 2019(COVID-19)and to save lives.Vaccine safety is one of the issues under surveillance and a possible correlation between vaccines and thyroid function has been reported.However,reports of the impact of coronavirus vaccines on those with Graves’disease(GD)are rare.CASE SUMMARY This paper presents two patients with underlying GD in remission,both developed thyrotoxicosis and one developed thyroid storm following the adenovirus-vectored vaccine(Oxford-AstraZeneca,United Kingdom).The objective of this article is to raise awareness regarding a possible association between COVID-19 vaccination and the onset of thyroid dysfunction in patients with underlying GD in remission.CONCLUSION Receiving either the mRNA or an adenovirus-vectored vaccine for SARS-CoV-2could be safe under effective treatment.Vaccine induced thyroid dysfunction has been reported,but the pathophysiology still not well understood.Further investigation is required to evaluate the possible predisposing factors for developing thyrotoxicosis especially in patients with underlying GD.However,early awareness of thyroid dysfunction following vaccination could avoid a lifethreatening event.

Multifocal papillary thyroid cancer in Graves’ disease: A case report

BACKGROUND Thyroid cancer is not commonly observed in patients with Graves’disease(GD).The presence of thyroid nodules in GD is not uncommon.However,a link bet-ween these two entities has been reported.Herein,we report the case of a patient with GD and thyroid cancer in Saudi Arabia,which has not been reported previously in our region.CASE SUMMARY A 26-year-old male patient with GD,receiving carbimazole for 2 years,presented to our hospital.His hyperthyroidism was controlled clinically and biochemically.On clinical examination,he was found to have a left-sided thyroid nodule.Ultra-sound revealed a 2.6 cm hypoechoic nodule with high vascularity.He was then referred for fine needle aspiration which showed that the nodule was highly suspicious for malignancy.The patient underwent total thyroidectomy and was diagnosed with multifocal classical micropapillary thyroid cancer.Post thyroid-ectomy he received radioactive iodine ablation along with levothyroxine replace-ment therapy.CONCLUSION Careful preoperative assessment and thyroid gland ultrasound might assist in screening and diagnosing thyroid cancer in patients with GD.

血清CYR61、IL-17、Klotho蛋白对Graves眼病病情的评估价值

目的 探讨血清高半胱氨酸蛋白61(CYR61)、白细胞介素-17(IL-17)、单向跨膜蛋白(Klotho)对Graves眼病(GO)病情的评估价值。方法 收集2020年1月至2023年10月于郑州大学第一附属医院眼五科诊治的103例患者的临床资料为研究对象,根据临床活动性评分(CAS)评估患者病情,将其分为活动期组42例及非活动期组61例,比较两组患者一般资料、临床基础指标[肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)、促甲状腺激素(TSH)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)及TSH受体抗体(TRAb)、CYR61、IL-17、Klotho蛋白水平及CAS评分],并通过多因素回归分析和ROC曲线分析GO眼病活动期的相关影响因素以及预测价值。结果 活动组Klotho、TSH、FT3、FT4、TRAb、TNF-α、IFN-γ、CYR61水平及CAS评分相较于非活动组更高,差异有统计学意义(t=7.953,4.364,5.232,6.100,4.364,7.344,4.890,6.541,6.995,13.283,P<0.05);经多因素回归分析得出TSH、FT3、FT4、TRAb、TNF-α、IFN-γ、IL-17、Klotho、CYR61合并CAS评分为影响GO眼病活动期的独立危险因素(OR=1.730,1.667,1.689,1.692,1.742,1.791,1.863,1.887,1.828,1.842,P<0.05);CYR61、IL-17、Klotho联合预测GO活动期的预测价值均高于三者单一检测,曲线下面积(AUC)分别为0.943,0.827,0.817,0.866(P<0.05)。结论 血清CYR61、IL-17、Klotho蛋白与GO活动期密切相关,三者联合联合检测对GO病情预测效能较好,评估价值确切。

Effect of lithium carbonate combined with131I therapy on thyroid function as well as the Fas/FasL expression in peripheral blood of patients with Graves disease and leukopenia

Objective:To study the effect of lithium carbonate combined with131I therapy on thyroid function as well as the Fas/FasL expression in peripheral blood of patients with Graves disease and leukopenia.Methods:124 patients with Graves disease and leukopenia treated in our hospital between May 2012 and October 2015 were randomly divided into the observation group (n=62) who received lithium carbonate combined with131I therapy and control group (n=62) who received131I therapy, and the outcome, autoantibody content, proportion of T lymphocyte subsets as well as the expression levels of Fas and FasL were compared between two groups of patients.Results: 3 months and 6 months after treatment, serum thyroid hormones free triiodothyronine (FT3) and serum free thyroxine (FT4) levels as well as autoantibodies TSAb, TGAb and TPOAb content of observation group were significantly lower than those of control group (P<0.05) while peripheral blood white blood cell count was significantly higher than that of control group (P<0.05);proportion of Treg cells in peripheral blood of observation group was significantly higher than that of control group (P<0.05) while the proportion of Th1 and Th2 cells as well as the expression levels of Fas and FasL were significantly lower than those of control group (P<0.05).Conclusions: Lithium carbonate combined with131I treatment of Graves disease complicated with leukopenia can reduce the thyroid hormone synthesis, increase white blood cell count and regulate the proportion of T lymphocyte subsets as well as the expression of Fas/FasL.

Peripheral blood NKT cell number and function in patients with Graves disease and their correlation with hyperthyroidism

Objective:To assess the peripheral blood NKT cell number and function in patients with Graves disease and study their correlation with hyperthyroidism.Methods: The patients who were diagnosed with Graves disease in our hospital between May 2014 and September 2016 were selected as GD group, and 55 healthy volunteers who received physical examination in our hospital during the same period were selected as control group. Peripheral blood was collected to determine the number of CD3+CD56+NKT cells, and serum was collected to detect the contents of cytokines and thyroid function indexes.Results: Peripheral blood CD3+CD56+NKT cell number in Graves disease group was significantly lower than that in control group;serum IL-2, IFN-γ, TNF-α, IL-10 and TGF-β contents in GD group were significantly lower than those in control group and positively correlated with peripheral blood CD3+CD56+NKT cell number while IL-4, IL-5, IL-17, FT3, FT4, TPOAb, TgAb and TRAb contents were significantly higher than those in control group and negatively correlated with peripheral blood CD3+CD56+NKT cell number.Conclusion:The abnormal reduction of peripheral blood NKT cell number in patients with Graves disease can affect the balance of Th1/Th2 and Th17/Treg and increase the TRAb secretion to cause hyperthyroidism.

夏枯草制剂治疗Graves病的有效性与安全性的系统评价

目的系统评价口服夏枯草制剂联合西医治疗Graves病的疗效及安全性,以期为Graves病的临床诊治提供循证医学证据。方法文章全面系统检索中文学术期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、万方数据库(WanfangData)、维普中文期刊全文数据库(VIP)四大中文数据库和PubMed、Embase、CochraneLibrary三大英文数据库,检索时间均从建库至2022年08月。采用Cochrane系统偏倚风险评估工具对纳入研究进行质量评估,并用RevMan 5.4.1软件对结局指标进行Meta分析。结果最终纳入8项随机对照试验,共784例患者。试验组均为口服夏枯草制剂联合西医治疗,对照组均为西医治疗。Meta分析结果表明,口服夏枯草制剂联合西医治疗在甲状腺功能及自身抗体的改善、缩小甲状腺腺体等方面的临床治疗总有效率高于对照组(RR=1.13,95%CI[1.10,1.26],P<0.00001),并且能够显著改善甲状腺肿的临床症状(MD=-0.39,95%CI[-0.67,-0.11],P=0.006),降低血清FT3水平(MD=-1.76,95%CI[-3.10,-0.43],P=0.01)及血清FT4水平(MD=-3.89,95%CI[-6.79,-1.00],P=0.008),提高血清促甲状腺激素(TSH)水平(MD=0.45,95%CI[0.05,0.86],P=0.03),改善甲状腺肿大情况(MD=-0.39,95%CI[-0.67,-0.11],P=0.006),缩小甲状腺左叶前后径(MD=-0.31,95%CI[-0.57,-0.06],P=0.02)、左叶左右径(MD=-0.24,95%CI[-0.32,-0.16],P<0.00001)、右叶前后径(MD=-0.30,95%CI[-0.47,-0.13],P=0.0004)、右叶左右径(MD=-0.21,95%CI[-0.33,-0.10],P=0.0004)。结论夏枯草制剂联合西医治疗对比单用西医治疗Graves病在整体疗效、改善甲状腺肿的临床症状、甲状腺激素水平,缩小甲状腺腺体有明显的优势,且较安全,但仍需后续大样本、高质量文献的支持。

多模态超声成像技术鉴别Graves病与慢性淋巴细胞性甲状腺炎的研究进展

Graves病与慢性淋巴细胞性甲状腺炎因缺乏典型临床症状极易误诊,及时诊断对改善患者生存质量至关重要,超声是评估甲状腺疾病的首要影像学手段。近年来,随着超微血流成像、剪切波弹性成像、计算机辅助诊断、超声造影等新技术出现,多模态超声诊断发展迅速,大量学者围绕甲状腺弥漫性病变展开研究。本文对多模态超声对Graves病与慢性淋巴细胞性甲状腺炎鉴别诊断的国内外现状及面临的问题进行综述,以期为临床诊疗中最大程度发挥多模态超声成像的技术优势,早期精准鉴别Graves病与慢性淋巴细胞性甲状腺炎提供理论依据。

Graves′病新型疗法的研究进展

Graves′病是一种自身免疫性疾病,其特征是存在刺激促甲状腺激素受体的自身抗体,导致甲状腺肿大及循环甲状腺激素过多。目前临床治疗Graves′病的主要方式包括抗甲状腺药物、放射性碘和甲状腺切除术,但药物治疗存在不良反应大、治疗周期长、复发率高等不足,而放射性碘和甲状腺切除术治疗患者无法避免地需要行终生甲状腺激素替代治疗,因此急需寻找新的治疗方案。目前正在研究的Graves′病的新型疗法包括生物制剂、小分子和肽免疫调节,这些疗法有望在不需要持续治疗的情况下成功使患者甲状腺功能趋于正常化。

Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier function.However, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could provide valuable insights into potential therapeutic strategies for Alzheimer's disease and related conditions.

Lowering of Blood Lipid Levels with a Combination of Pitavastatin and Ezetimibe in Patients with Coronary Heart Disease:A Meta-Analysis

Objectives:According to the findings of randomized controlled trials,blood lipid levels in patients with coronary heart disease(CHD)can be significantly decreased through a combination of pitavastatin and ezetimibe;however,the effects and clinical applications of this treatment remain controversial.This meta-analysis was aimed at objectively assessing the efficacy and safety of pitavastatin and ezetimibe in lowering blood lipid levels.Design:Relevant studies were retrieved from electronic databases,including PubMed,Cochrane Library,Embase,China National Knowledge Infrastructure,VIP,and WanFang Data,from database inception to June 8,2022.The lev-els of low-density lipoprotein cholesterol,total cholesterol,triglycerides,and high-density lipoprotein cholesterol in patients’serum after treatment were the primary endpoint.Results:Nine randomized controlled trials(2586 patients)met the inclusion criteria.The meta-analysis indi-cated that pitavastatin plus ezetimibe resulted in significantly lower levels of LDL-C[standardized mean difference(SMD)=−0.86,95%confidence interval(CI)(−1.15 to−0.58),P<0.01],TC[SMD=−0.84,95%CI(−1.10 to−0.59),P<0.01],and TG[SMD=−0.59,95%CI(−0.89 to−0.28),P<0.01]than pitavastatin alone.Conclusions:Pitavastatin plus ezetimibe significantly decreased serum LDL-C,TC,and TG levels in patients with CHD.

外周血CD4^(+)T、CD8^(+)T细胞及免疫活化分子CD38、IL-2R表达水平在Graves眼病患者中的临床意义

目的研究Graves眼病(GO)患者外周血CD4^(+)T、CD8^(+)T细胞及免疫活化分子CD38、IL-2R水平的临床意义。方法选取2022年1月至2023年1月我院收治的80例Graves病(GD)患者为GD组,65例GO患者为GO组,根据CAS评分将GO组患者分为活动期组(26例)和非活动期组(39例),另选50例体检中心健康者为对照组。比较各组血清甲状腺功能、甲状腺相关抗体及外周血各细胞因子水平,分析GO患者外周血各细胞因子水平与甲状腺功能、甲状腺相关抗体、CAS评分的相关性,并分析外周血各细胞因子对GO疾病活动性的预测价值。结果GO组FT3、FT4低于GD组,高于对照组,GD组高于对照组(P<0.05);GO组TSH高于GD组,低于对照组,GD组低于对照组(P<0.05);GO组、GD组TGAb、TPOAb、TRAb、CD4^(+)T高于对照组(P<0.05);GO组、GD组CD8^(+)T低于对照组(P<0.05);GO组CD4^(+)/CD8^(+)T、CD4^(+)CD38^(+)T、CD8^(+)CD38^(+)T、IL-2R高于GD组和对照组,GD组高于对照组(P<0.05)。GO患者活动期组CD4^(+)/CD8^(+)T、CD4^(+)CD38^(+)T、CD8^(+)CD38^(+)T、IL-2R高于非活动期组(P<0.05)。CD4^(+)/CD8^(+)T、CD8^(+)CD38^(+)T与CAS评分呈正相关(P<0.05);CD4^(+)CD38^(+)T与TRAb、CAS评分呈正相关(P<0.05);IL-2R与FT4、TRAb、TPOAb、CAS评分呈正相关(P<0.05)。CD4^(+)/CD8^(+)T、CD4^(+)CD38^(+)T、CD8^(+)CD38^(+)T、IL-2R联合检测预测GO患者疾病活动性的AUC值为0.930,高于外周血四者单独检测(AUC=0.736、0.749、0.668、0.699,P<0.05)。结论外周血CD4^(+)/CD8^(+)T、CD4^(+)CD38^(+)T、CD8^(+)CD38^(+)T、IL-2R联合预测GO活动性的临床价值更高。

Evaluating the causal relationship between human blood metabolites and gastroesophageal reflux disease

BACKGROUND Gastroesophageal reflux disease(GERD)affects approximately 13% of the global population.However,the pathogenesis of GERD has not been fully elucidated.The development of metabolomics as a branch of systems biology in recent years has opened up new avenues for the investigation of disease processes.As a powerful statistical tool,Mendelian randomization(MR)is widely used to explore the causal relationship between exposure and outcome.AIM To analyze of the relationship between 486 blood metabolites and GERD.METHODS Two-sample MR analysis was used to assess the causal relationship between blood metabolites and GERD.A genome-wide association study(GWAS)of 486 metabolites was the exposure,and two different GWAS datasets of GERD were used as endpoints for the base analysis and replication and meta-analysis.Bonferroni correction is used to determine causal correlation features(P<1.03×10^(-4)).The results were subjected to sensitivity analysis to assess heterogeneity and pleiotropy.Using the MR Steiger filtration method to detect whether there is a reverse causal relationship between metabolites and GERD.In addition,metabolic pathway analysis was conducted using the online database based MetaboAnalyst 5.0 software.RESULTS In MR analysis,four blood metabolites are negatively correlated with GERD:Levulinate(4-oxovalerate),stearate(18:0),adrenate(22:4n6)and p-acetamidophenylglucuronide.However,we also found a positive correlation between four blood metabolites and GERD:Kynurenine,1-linoleoylglycerophosphoethanolamine,butyrylcarnitine and guanosine.And bonferroni correction showed that butyrylcarnitine(odd ratio 1.10,95% confidence interval:1.05-1.16,P=7.71×10^(-5))was the most reliable causal metabolite.In addition,one significant pathways,the"glycerophospholipid metabolism"pathway,can be involved in the pathogenesis of GERD.CONCLUSION Our study found through the integration of genomics and metabolomics that butyrylcarnitine may be a potential biomarker for GERD,which will help further elucidate the pathogenesis of GERD and better guide its treatment.At the same time,this also contributes to early screening and prevention of GERD.However,the results of this study require further confirmation from both basic and clinical real-world studies.

Protocol to study the effects of AMPK-mTOR/PINK-Parkin dual signaling pathways on the formation of coronary heart disease showing blood stasis symptom pattern based on traditional Chinese medicine theory of“heart governing blood and vessels”

In this study,we aim to combine gene transfection techniques with the modeling methods previously employed by the research group to deeply investigate the corresponding theories of traditional Chinese medicine regarding“myocardial energy metabolism”and“aortic thrombosis”.Our goal is to elucidate the biological mechanism underlying the occurrence and development of coronary heart disease with blood stasis syndrome from the perspectives of“heart and vessels”and“Qi(in traditional Chinese medicine,it refers to the most fundamental and subtle substances that constitute the human body and maintain life activities.At the same time,it also has the meaning of physiological function.In terms of traditional Chinese medicine,Qi and different words are used together to express different meanings)and blood”.The research content is divided into four modules as follows:1.establishment of an animal model of coronary heart disease with blood stasis syndrome through fibrinogen overexpression.2.Investigation of the mitochondrial quality control system in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.3.Study of platelet autophagy in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.4.Examination of the relationship between the AMPK-mTOR pathway and metabolism in platelet autophagy of coronary heart disease with blood stasis syndrome under fibrinogen overexpression.Ninety-six Sprague Dawley rats will be randomly assigned to the following groups:control group,model group,fibrinogen group and adeno-associated virus group.All rats will undergo a 14-week model construction process,and modern molecular biology methods will be employed to evaluate the model and examine relevant research indicators.The obtained data will be analyzed according to a predefined statistical analysis plan.

与Graves’Disease发病机制相关的基因研究

背景Graves’Disease(GD)是一种常见的自身免疫性疾病,但其发病机制尚不明确。目的通过对公共基因芯片数据的分析,找出与GD发病可能相关的基因。方法在GEO数据库和ArrayExpress数据库中检索“Graves’Disease”,得到GSE71956和E-MEXP-2612(截至2019-04-02)。利用R语言的“Limma”包对基因芯片的原始数据进行标准化处理并找出差异基因。差异基因共包括对照CD4细胞与GD患者CD4细胞的对比(C-GD CD4)、对照CD8细胞与GD患者CD8细胞的对比(C-GD CD8)、对照者甲状腺组织与短病程GD患者甲状腺组织的对比(C-S)、对照者甲状腺组织与长病程GD患者甲状腺组织的对比(C-L)、短病程GD患者甲状腺组织与长病程GD患者甲状腺组织的对比(S-L)。再对差异基因进行多重比较及功能注释分析。结果维恩图显示,KLF9、RGS1基因同时存在于C-GD CD4、C-GD CD8与C-L差异基因中。氨基酸和类固醇代谢基因可能与GD的发病相关。FMO2、CALHM6和C7基因同时存在于C-S、C-L、S-L差异基因中。长病程和短病程GD患者甲状腺组织CALHM6基因表达水平高于对照者,长病程GD患者CALHM6基因表达水平高于短病程GD患者;长病程和短病程GD患者甲状腺组织FMO2和C7基因表达水平低于对照者,长病程GD患者FMO2和C7基因表达水平低于短病程GD患者(P<0.05)。结论GD的发病可能与KLF9、RGS1的异常表达及氨基酸和类固醇代谢有关,FMO2、CALHM6、C7基因可能与GD的病程相关。

Association of Polymorphisms of rs179247 and rs12101255 in Thyroid Stimulating Hormone Receptor Intron 1 with an Increased Risk of Graves' Disease:A Meta-analysis

The polymorphisms of thyroid stimulating hormone receptor（TSHR） intron 1 rs179247 and rs12101255 have been found to be associated with Graves＇ disease（GD） in genetic studies. In the present study, we conducted a meta-analysis to examine this association. Two reviewers systematically searched eligible studies in Pub Med, Web of Science, Embase and China Biomedical Literature Database（CBM）. A meta-analysis on the association between GD and TSHR intron 1 rs179247 or rs12101255 was performed. The odd ratios（OR） were estimated with 95% confidence interval（CI）. Meta package in R was used for the analyses. Seven articles（13 studies） published between 2009 and 2014, involving 5754 GD patients and 5768 controls, were analyzed. The polymorphism of rs179247 was found to be associated with an increased GD risk in the allele analysis（A vs. G： OR=1.40, 95% CI=1.33–1.48） and all genetic models（AA vs. GG： OR=1.94, 95% CI=1.73–2.19; AA＋AG vs. GG： OR=1.57, 95% CI=1.41–1.74; AA vs. AG＋GG： OR=1.54, 95% CI=1.43–1.66）. The site rs12101255 also conferred a risk of GD in the allele analysis（T vs. C： OR=1.50, 95% CI=1.40–1.60） and all genetic models（TT vs. CC： OR=2.22, 95% CI=1.92–2.57; TT＋TC vs. CC： OR=1.66, 95% CI=1.50–1.83; TT vs. TC＋CC： OR=1.74, 95% CI=1.53–1.98）. Analysis of the relationship between rs179247 and Graves＇ ophthalmopathy（GO） showed no statistically significant correlation（A vs. G： OR=1.02, 95% CI=0.97–1.07）. Publication bias was not significant. In conclusion, GD is associated with polymorphisms of TSHR intron 1 rs179247 and rs12101255. There is no association between rs179247 SNPs and GO.

Effects of Combined Inhalation of Budesonide,Formoterol,and Tiotropium Bromide on Arterial Blood Gas and Pulmonary Function Indexes in Patients with Chronic Obstructive Pulmonary Disease

Objective:To analyze the effect of combined inhalation of budesonide formoterol and tiotropium bromide on arterial blood gas and pulmonary function indexes in patients with chronic obstructive pulmonary disease(COPD).Methods:100 patients with COPD treated from January to December 2022 were selected as observation objects,and were divided into a control group(n=50,in which budesonide and formoterol were administered)and an experimental group(n=50,the treatment drug was budesonide formoterol combined with tiotropium bromide)according to the computer grouping method,and compared the treatment results.Results:(i)Before treatment,there was no difference in the partial pressure of carbon dioxide and partial pressure of oxygen between the control group and the experimental group(P>0.05);after treatment,the partial pressure of carbon dioxide and partial pressure of oxygen in the experimental group were higher than those in the control group,with significant differences(P<0.05).(ii)Before treatment,there was no difference in forced vital capacity(FVC),forced expiratory volume in one second(FEV1),FEV1/FVC between the control group and the experimental group(P>0.05);after treatment,the FVC,FEV1,and FEV1/FVC in the experimental group were significantly higher than those in the control group(P<0.05).(iii)There was no difference in the levels of CRP,IL-6,and TNF-αbetween the control group and the experimental group(P>0.05);after treatment,the levels of CRP,IL-6,and TNF-αin the experimental group were lower than those in the control group,with significant differences(P<0.05).(iv)Compared to the total incidence of adverse reactions in the control group(28.00%),the incidence of total adverse reactions in the experimental group was lower at 10.00%,and the difference was significant(P<0.05).Conclusion:The combined inhalation of budesonide and formoterol with tiotropium bromide has demonstrated a clear therapeutic efficacy and safety in treating chronic obstructive pulmonary disease.This treatment approach effectively enhances arterial blood gas levels and lung function,showing promising potential for widespread application.

Role of color Doppler in differentiation of Graves' disease and thyroiditis in thyrotoxicosis

AIM:To evaluate the role of thyroid blood flow assessment by color-flow Doppler ultrasonography in the differential diagnosis of thyrotoxicosis and compare it to technetium pertechnetate thyroid scanning. METHODS:Twenty-six patients with thyrotoxicosis were included in the study. Clinical history was taken and physical examination and thyroid function tests were performed for all patients. Thyroid autoantibodies were measured. The thyroid glands of all patients were evaluated by gray scale ultrasonography for size, shape and echotexture. Color-flow Doppler ultrasonography of the thyroid tissue was performed and spectral flow analysis of both inferior thyroid arteries was assessed. Technetium99 pertechnetate scanning of the thyroid gland was done for all patients. According to thyroid scintigraphy, the patients were divided into two groups:18 cases with Graves' disease and 8 cases with Hashimoto's thyroiditis. All patients had suppressed thyrotropin. The diagnosis of Graves' disease and Hashimoto's thyroiditis was supported by the clinical picture and follow up of patients. RESULTS:Peak systolic velocities of the inferior thyroid arteries were significantly higher in patients with Graves' disease than in patients with thyroiditis (P = 0.004 in the right inferior thyroid artery and P = 0.001 in left inferior thyroid artery). Color-flow Doppler ultrasonography parameters demonstrated a sensitivity of 88.9% and a specificity of 87.5% in the differential diagnosis of thyrotoxicosis. CONCLUSION:Color Doppler flow of the inferior thyroid artery can be used in the differential diagnosis of thyrotoxicosis, especially when there is a contraindication of thyroid scintigraphy by radioactive material in some patients.

Graves’ Disease as a Late Manifestation of Immune Reconstitution Syndrome after Highly Active Antiretroviral Therapy in an HIV-1 Infected Patient

Context: Highly active antiretroviral therapy (HAART) inhibits the HIV replication and consequently increases CD4 levels and decreases viral load. This immune system improvement can trigger various immunological phenomena, entity called Immune Reconstitution Syndrome (IRS). Graves’ disease is a late Immune Reconstitution consequence. Patient: We report the case of a 48 years old man with HIV infection who developed Graves’ disease three years after he was on effective HAART because of the Immune Reconstitution Syndrome. At presentation he had a very low CD4 T-cell count (17 cells/μL). When he started HAART he presented a lipodystrophy syndrome. HAART was changed because of the persistent low CD4-T cells count (less than 100 cell/μL). Afterwards serum lipid levels began to decrease and that was the first manifestation of Graves’ disease, which was diagnosed when CD4 T-cells increased up to 343 cell/μL. Our patient developed Graves’ disease 36 months after initiating effective HAART with protease inhibitors which was coincident with viral suppression and a rise of CD4 T cells. Conclusion: The most immunosuppressed patients with a CD4 T cell count less than 100 cells/μL are at greatest risk for the development of Immune Reconstitution Syndrome after HAART initiation. We conclude that clinicians will have to consider the importance of the early diagnosis of thyroid disease to bring an adequate treatment.