Background and Objective: IgG4-related Hashimoto's thyroiditis (IgG4 HT) is characterized by rapid progression and may be associated with an increased risk of papillary thyroid carcinoma (PTC). The diagnosis of IgG4 HT relies primarily on postoperative pathological analysis. Early identification of IgG4 HT is crucial for guiding patient management. This study assessed the possibility of thyroid core needle biopsy (CNB) in diagnosing IgG4 HT. Methods: One hundred and twenty HT patients who underwent color Doppler-guided CNB and subsequent thyroid surgery were collected in Peking University First Hospital. Clinical, serological, sonographic, and histopathological features were also collected. The numbers of IgG4 and IgG plasma cells were counted in five high power fields (HPF), then the average numbers of IgG4+ and IgG+ plasma cells per HPF were calculated respectively. Results: Based on the IgG4 and IgG immunohistochemistry results of 120 surgical specimens, cases were subclassified as IgG4 HT (n = 18) and non-IgG4 HT (n = 102) groups by the thyroid-specific diagnostic criteria (IgG4+ plasma cells > 20/HPF and IgG4+/IgG+ plasma cell ratio > 30%). CNB samples from IgG4 HT patients were subsequently subjected to IgG4/IgG immunostaining. However, only eight of the corresponding CNB tissues met the IgG4 HT diagnostic criteria. The remaining ten patients had IgG4+ positivity ranged in 10-20 cells/HPF and an IgG4+/IgG+ plasma cell ratio ranging from 20% to 67%. Histopathological characteristics of thyroid tissue were consistent between the surgical and CNB samples. Conclusion: IgG4/IgG immunostaining of CNB samples derived from thyroid tissue may serve as a valuable tool for supporting the diagnosis of IgG4 HT.

BACKGROUND:Autoimmune thyroid disease (AITD) and major depressive disorder (MDD) are common genetic diseases. The comorbidity of AITD and MDD has been widely demonstrated by large amounts of epidemiological studies. However, the genetic architectures of the comorbidity remain unknown. METHODS:We use large-scale GWAS summary data and novel genetic statistical methods to assess the genetic correlation and potential causality between AITD and MDD disorders. We perform cross-trait GWAS meta-analyses to identify genetic risk variants not previously associated with the individual traits. And we use summary-data-based mendelian randomisation to identify putative functional genes shared between diseases. RESULTS:Both global and local genetic correlation study confirmed the genetic correlation of AITD and MDD. Through multi-trait analysis of GWAS (MTAG), we identified 112 SNPs associated with the conjoint phenotype, but not with individual traits. Mendelian randomisation confirmed the causal relationship between MDD (exposure) and AITD (outcome). The summary-based mendelian randomisation study found two plausible functional genes for AITD and MDD comorbidity. CONCLUSIONS:AITD and MDD are genetically correlated in global and local chromosomal regions. MR analyses support a putative casual effect of MDD on AITD risk, though residual pleiotropy or confounding cannot be fully excluded. These findings highlight the need for triangulation with experimental and longitudinal studies to confirm causality.

There is no approved effective drug for diabetic peripheral neuropathic pain (DPNP) in China. Gabapentinoids including mirogabalin have shown promise, although data in Chinese patients are scarce. This phase 3, multicenter, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of mirogabalin for treating DPNP in China. Mirogabalin was administered at 5 mg twice daily for the first week and uptitrated to 15 mg twice daily for a total duration of 14 weeks. The primary efficacy endpoint was the change from baseline in weekly average daily pain score (ADPS) at week 14; secondary endpoints included the ADPS responder rate, Short-Form McGill Pain Questionnaire visual analogue scale score, patient global impression of change (PGIC), average daily sleep interference score (ADSIS), EuroQol 5-dimensions 5-levels (EQ-5D-5L), and incidence of treatment-emergent adverse events (TEAEs). Of 393 patients (mirogabalin, n = 196; placebo n = 197), the mean age was 58.2 years (mirogabalin, 58.7 years; placebo, 57.7 years) and 54.2

ObjectiveTo identify risk factors contributing to the development of postpartum hypothyroidism in women newly diagnosed with subclinical hypothyroidism (SCH) during the first trimester of pregnancy (T1). Additionally, this study aimed to explore the impact of thyroid peroxidase antibody (TPOAb) titers trajectories throughout pregnancy and postpartum.MethodsThyroid hormone levels and thyroid autoantibody titers were collected from T1 to the 12th month postpartum. Logistic regression analysis was employed to identify independent risk factors for hypothyroidism at the 12th month postpartum and to develop a prediction model. Model performance was assessed through discrimination, calibration, and clinical applicability, with internal validation using the bootstrap resampling method. Growth Mixture Modeling was applied to delineate the trajectory of TPOAb titers during pregnancy and postpartum, and logistic regression analysis was conducted to investigate the influence of these trajectories on the occurrence of postpartum hypothyroidism.ResultsAt the 12th month postpartum, hypothyroidism was either newly diagnosed or persisted in 76 of 209 cases (36.36%). Several significant risk factors for postpartum hypothyroidism were identified, including multiparity, positive TPOAb in T1, positive TPOAb and thyroglobulin antibody in T1, serum thyroid-stimulating hormone levels at SCH diagnosis in T1, and the final dose of levothyroxine in the third trimester. A prediction model was constructed and presented with a nomogram. Furthermore, a higher trajectory of serum TPOAb titer during pregnancy and postpartum emerged as a predictive factor for hypothyroidism at the 12th month postpartum.ConclusionWomen with elevated TPOAb titers during pregnancy and postpartum necessitate ongoing and vigilant monitoring of thyroid function, even after childbirth.

This study aims to develop a non-invasive diagnosis model using machine learning (ML) for identifying high-risk IgG4 Hashimoto’s thyroiditis (HT) patients. A retrospective cohort of 93 HT patients and a prospective cohort of 179 HT patients were collected. According to the immunohistochemical and pathological results, the patients were divided into IgG4 HT group and non-IgG4 HT group. Serum TgAb IgG4 and TPOAb IgG4 were detected by ELISAs. A logistic regression model, support vector machine (SVM) and random forest (RF) were used to establish a clinical diagnosis model for IgG4 HT. Among these 272 patients, 40 (14.7

Background: To explore whether IgG4 is involved in the pathogenesis of IgG4 HT. Methods: Serum TgAb IgG4 and TPOAb IgG4 were measured in IgG4 HT and non-IgG4 HT. C1q, mannose-binding lectin (MBL), Bb, C3d, C4d, and membrane attack complex (MAC) in thyroid tissues from IgG4 HT, non-IgG4 HT, and controls were examined by immunohistochemistry. We assessed IgG4 and MAC deposition in mouse thyroid by immunohistochemistry after injecting purified IgG4 into mice. The glycosylation patterns of TgAb IgG4 from IgG4 HT were identified by MALDI-TOF-MS. The ability of IgG4 to bind to MBL before and after deglycosylation was assessed by ELISA. MBL and MAC fluorescence were detected in thyrocytes after the addition of IgG4 or deglycosylated IgG4. Results: Serum TgAb IgG4 and TPOAb IgG4 levels were significantly higher in the IgG4 HT group. MBL, Bb, C3d, C4d, and MAC levels were significantly higher in the thyroid tissues of IgG4 HT than in non-IgG4 HT (all P < 0.001). IgG4 colocalized with MBL by immunofluorescence. In mice, follicular cell structure disruption was observed after the injection of IgG4 from IgG4 HT, as well as the colocalization of IgG4 with MAC. High levels of TgAb IgG4 glycosylation patterns, including monogalactose glycan (G1F), galactose-deficient glycan (G0F), and high-mannose glycan (M5), were detected in IgG4 HT. After deglycosylation, IgG4 reduced its ability to bind to MBL, and there was low MBL and MAC activation in thyrocytes. Conclusion: High levels of IgG4 glycosylation patterns, including G1F, G0F, and M5, may activate the complement lectin pathway, thereby participating in the pathogenesis of IgG4 HT.

Background:Hashimoto's thyroiditis (HT) can be divided into IgG4 HT and non-IgG4 HT based on IgG4 and IgG immunohistochemical staining. In clinical practice, it is often necessary to identify diseases such as primary thyroid lymphoma (PTL) and IgG4 HT when a patient presents with a rapidly enlarged thyroid. The aim of our study was to uncover the differential points between the two diseases. Methods:Clinical information from 19 IgG4 HT and 10 PTL patients was obtained from the patients' medical records, including age, sex, main clinical manifestation, thyroid functional status, the presence of serum anti-thyroid peroxidase antibodies, anti-thyroglobulin antibodies, and thyroid ultrasonography results. Thyroid sections from all patients were collected to detect IgG4 and IgG expression by immunohistochemical staining. Results:The IgG4 HT patients were significantly younger than those in the PTL group (39.68 ± 10.95 vs 66.20 ± 10.23 years, P < 0.001). There were no significant differences in the sex distribution or TgAb- or TPOAb-positive rates. The PTL group had a higher prevalence of clinical hypothyroidism than the IgG4 HT group (P = 0.016). In the PTL group, thyroid lesions were more likely to exhibit hypoechogenicity (6/6 vs 1/19, P < 0.001) on ultrasound images. In the PTL group, two patients met the immunohistochemical cut-off value of the criteria for IgG4 HT. Conclusions:Simply relying on immunohistochemistry for IgG4 cannot diagnose IgG4 HT correctly when a patient presents with rapid thyroid enlargement. A combination of clinical and pathological analyses will help distinguish IgG4 HT from PTL which may be with abundant IgG4-positive plasma cells.

Objective: To investigate complement components expression in both thyroid tissues and serum from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD), and papillary thyroid cancer (PTC).Methods: C1q, mannose binding lectin (MBL), Bb, C4d, C3d and membrane attack complex (MAC) (C5b-9) deposition and complement regulate proteins (CD46, CD55 and CD59) expression in thyroid tissues from HT, GD, PTC, and control groups were examined by IHC. C1q, MBL, Bb, C4d, C3a, and soluble C5b-9 (sC5b-9) serum levels in the HT, GD, PTC, and healthy donor (HD) groups were measured by ELISAs.Results: MAC deposition was detected in thyroid tissues in the HT, GD and PTC groups, but not the control group. MBL, Bb, C4d, C3d and MAC staining intensities in thyroid tissues were significantly higher in the HT and PTC groups than in the control group (all P < 0.05). The C1q level was higher in HT tissues than in control tissues (both P < 0.05). No complement component had a significant difference in staining intensities between the GD and control groups. CD55 and CD59 expression levels in thyroid tissues were higher in the PTC group than in the HT, GD and control groups (all P < 0.05). Similarly, CD46 levels were higher in HT tissues than in control tissues. Bb, C4d, C3a and sC5b-9 serum levels were significantly increased in HT, GD and PTC patients compared with HDs (all P < 0.05).Conclusion: Complement is overactivated in HT and PTC, but not in GD. All the three pathways are activated in HT, and the MBL and alternative complement pathways are activated in PTC. These distinct complement acti-vation profiles may participate in HT, GD and PTC pathogenesis.

: Empty sella syndrome (ESS) contains serious of symptoms such as intractable headache, pituitary insufficiency, impaired vision and endocrine dysfunctions due to an anatomical condition of empty sella. Pituitary crisis is a critical clinical syndrome characterized by "shock, coma and metabolic disorders". Here we report a rare case of empty sella syndrome complicated with pituitary crisis. The diagnosis was established through hypoglycemia, electrolyte disorders, endocrine dysfunctions and magnetic resonance images. The patient received hormone replacement therapy and the disorders were corrected properly.

羟苯磺酸钙是一种血管保护药物,具有抗炎、抗氧化应激、改善内皮功能紊乱等多种作用.研究表明羟苯磺酸钙可有效改善糖尿病视网膜病变患者的临床症状,并延缓视网膜病变的进展,同时还可以降低糖尿病肾病患者的尿白蛋白排泄率.此外,羟苯磺酸钙主要以原型双通道排泄,肝、肾负担轻,临床不良反应少,已被多个指南/专家共识推荐用于治疗糖尿病微血管病变.

目的 探讨Kwak TI-RADS与ACR TI-RADS对儿童甲状腺结节的诊断效能及应用价值.方法 回顾性分析68个儿童甲状腺结节,构建受试者工作特性曲线(ROC),分析ACR TI-RADS和Kwak TI-RADS对儿童甲状腺结节的应用价值.结果 两种分类方法恶性度均随分类级别增加而增高,以Kwak TI-RADS 4b类和ACR TI-RADS 4类为最佳诊断点,Kwak TI-RADS的特异度略高于ACR TI-RADS(54.5％:51.5％,P<0.05),但两者灵敏度、PPV、NPV、AUC均无统计学意义(P>0.05);按照ACR TI-RADS成人推荐甲状腺结节穿刺标准,28％(7/25)儿童恶性结节没有分入建议穿刺组.结论 Kwak TI-RADS和ACR TI-RADS对儿童甲状腺结节分类均具有较好的指导作用,Kwak TI-RADS具有相对较高特异度,但儿童甲状腺结节在应用ACR TI-RADS推荐的穿刺标准尚需进一步研究.

Objective: Thyroglobulin antibodies (TgAb), principally comprising immunoglobulin G (IgG), are frequently found in healthy individuals. Previously, we showed that the glycosylation levels of TgAb IgG differed across various thyroid diseases, suggesting an important role of glycosylation on antibodies in the pathogenesis of thyroid diseases. Since IgG1 and IgG4 are the primary TgAb IgG subclasses, this study aimed to investigate the glycosylation of TgAb IgG1 and IgG4 subclasses in thyroid diseases. Methods: TgAb IgG was purified by affinity chromatography from the serum of patients with Hashimoto’s thyroiditis (HT) (n = 16), Graves’ disease (GD) (n = 8), papillary thyroid carcinoma (PTC) (n = 6), and PTC with histological lymphocytic thyroiditis (PTC-T) (n = 9) as well as healthy donors (n = 10). TgAb IgG1 and IgG4 concentrations were determined by enzyme-linked immunosorbent assay, and a lectin microassay was used to assess TgAb IgG1 and IgG4 glycosylation. Results: Significantly elevated mannose, sialic acid, and galactose levels on TgAb IgG1 were found in HT and PTC patients compared to GD patients and healthy controls (all p < 0.05). The mannose, sialic acid, and core fucose levels on TgAb IgG1 in PTC-T patients were higher than in healthy controls (all p < 0.05). Additionally, TgAb IgG1 from PTC-T patients exhibited lower sialylation than that from patients with PTC and higher fucosylation than that from patients with HT (both p < 0.05). However, TgAb IgG4 glycosylation did not differ among the five groups (p < 0.05). Conclusion: Our study describes different distributions of TgAb IgG1 glycosylation in various thyroid diseases. The aberrantly increased glycosylation levels of TgAb IgG1 observed in HT, PTC, and PTC-T might be indicative of immune disorders and participate in the pathogenesis of these diseases.

Riedel’s thyroiditis (RT) is a very rare chronic fibrosing thyroiditis that is often associated with multifocal fibrosclerosis. Although the relationship of RT and IgG4‐related disease (IgG4‐RD) has been suggested, the expression of IgG and IgG4 in thyroid tissues of patients with RT has seldom been studied.

IgG4 Hashimoto's thyroiditis (HT) and Riedel thyroiditis (RT) are the two main types of IgG4-related thyroiditis.IgG4 HT is associated with rapid progress, higher degree of fibrosis and higher risks of papillary thyroid carcinoma. RT is a rare chronic fibrosing disorder characterized by a hard, infiltrative lesion in the thyroid gland, which has been claimed to be part of a systemic IgG4-related disease. Clinical characteristics, updated diagnostic criteria and current standard of management for these two diseases will be discussed in this review.

IgG4相关性疾病(IgG4-RD)是一组以密集的淋巴细胞、浆细胞浸润,IgG4+浆细胞比例明显升高,席轮状纤维化及部分患者血清IgG4水平升高为特点的免疫介导的纤维炎性疾病.该疾病临床谱广泛,可以同时或先后累及多个组织、器官.2005年有研究者发现约25％的自身免疫性胰腺炎患者伴有甲状腺功能减退症(简称甲减),并且在这部分患者血清中可以检测到甲状腺球蛋白抗体(TgAb)水平的明显升高…,因此,IgG4与甲状腺的关系开始得到关注.目前文献报道的IgG4与甲状腺的相关研究主要涉及4种疾病:IgG4型桥本甲状腺炎(HT)、里德尔甲状腺炎(RT)、血清IgG4升高型HT及血清IgG4升高型Graves病(GD)[2].本文对上述疾病的研究现状作简要综述,以提高临床医师对该类疾病的认识,为临床诊治提供帮助.

Schwannoma is a proliferation of neoplastic Schwann cells. Schwannomas comprise 8-10% of all primary intracranial tumors. Primary intraorbital schwannoma arising from the ciliary nerves in the uvea, which accounts for 1-2% of all intracranial tumors, is a rare intraocular neoplasm. Intraocular schwannoma frequently masquerades as melanoma, reflecting the difficulty in clinically distinguishing it from malignant melanoma and the requirement for a histopathological diagnosis. The aim of the present study was to report a case series of 3 patients diagnosed with intraocular schwannoma at the Department of Ophthalmology, Peking University People's Hospital (Beijing, China). Patients with intraocular schwannoma were identified by searching the computerized database and patient medical records of the Department of Ophthalmology of Peking University People's Hospital. The patients (2 men and 1 woman; mean age, 34 years; age range, 25-48 years) were all treated by trans-scleral local resection, and schwannoma was confirmed by biopsy. The study found that choroidal schwannoma has a variety of clinical manifestations, with iridodialysis, subluxation of the lens and exudative detachment of the retina observed. The present study indicates that a pathological biopsy is required for diagnosis and that the optimal therapy is local resection.

SummaryBackgroundHashimoto's thyroiditis (HT) with serum IgG4 concentrations greater than 135 mg/dL can be diagnosed as elevated serum IgG4 HT. HT can also be classified into IgG4 HT and non‐IgG4 HT based on an immunohistochemistry analysis of IgG4. The aim of our study was to determine the relationship between elevated serum IgG4 HT and IgG4 HT.MethodBoth thyroid tissues and serum samples stored before pathological examination from 93 patients with HT were collected. The serum levels of IgG, IgG4, TgAb IgG, TgAb IgG4, TPOAb IgG and TPOAb IgG4 were measured by ELISAs. The expression levels of IgG4, IgG and TGF‐β1 in thyroid tissues were detected by immunohistochemistry.ResultsPatients with HT were divided into two groups: elevated serum IgG4 HT (n = 12) and nonelevated serum IgG4 HT (n = 81). Hypothyroidism was found in 5 of 12 cases (41.7%) in the elevated serum IgG4 HT group and 10 of 81 cases (12.3%) in the nonelevated serum IgG4 HT group (P = .023). Serologically, there were no significant differences in the levels of TgAb IgG, TPOAb IgG, TgAb IgG4 and TPOAb IgG4 between the two groups, and the expression of TGF‐β1 in thyroid tissues was not significantly different between the groups. Most importantly, the frequency of patients who satisfied the criteria for IgG4 HT diagnosis was comparable (25% vs 20.9%, P = .756).ConclusionsThe measurement of serum IgG4 allows the identification of patients with HT closely associated with hypothyroidism. However, our study demonstrated that elevated serum IgG4 HT is not equivalent to IgG4 HT.

Obiective Tend to explore the correlation between thyroid function and the severity of coronary artery lesions in chinese coronary heart disease(CHD)patients. Methods A total of 558 patients who underwent coronary angiography at the cardiology department of Peking University First Hospital from January 2013 to June 2015 were enrolled in this retrospective study. All patients were divided into coronary heart disease group and non-coronary heart disease group. Thyroid hormone levels were tested in all patients before angiography,and clinical characteristics,lipid profiles and SYNTAX scores were also obtained. Results Of the 558 patients,409 were diagnosed of CHD(73.3％),and among them,5 patients were hyperthyroid/subclinical hyperthyroid(1.2％),13 patients were hypothyroid/subclinical hypothyroid(3.2％),14 patients had euthyroid sicknesssyndrome(ESS)(3.2％),377 patients were euthyroid(92.2％). Among the 149 non-CHD patients(26.7％),3 patients were subclinical hyperthyroid(2.0％),8 patients were hypothyroid/subclinical hypothyroid(5.4％),2 patients were ESS(1.3％),172 patients were euthyroid(91.3％). The proportion of patients with ESS in the CHD group was significantly higher than that of the non-CHD group (3.4％ vs. 1.3％,P=0.018). Except for the patients with ESS,FT3 level was significantly lower the in CHD group than that in the non-CHD group[(4.52±0.57)pmol/L vs.(4.65±0.63)pmol/L,P=0.015]. There were no significant differences in FT4,T3,T4 levels between the two groups(P>0.05). In the CHD group,there was an association between the SYNTAX score groups and free triiodothyronine(FT3)levels(F=6.260,P=0.002). A significant correlation was also observed between the FT3 level and the number of coronary artery lesions(F=5.691, P=0.004). There was no correlation between the SYNTAX score groups or number of coronary artery lesions and thyroid hormone levels,respectively. There were no correlations between lipid profiles and thyroid function. Patients were further divided into three subgroups according to their serum TSH levels. The prevalence of CHD is significantly higher in the subgroup with elevated TSH(85.7％)than in the subgroup with normal TSH(68.6％, P=0.022). Conclusions FT3 level is weakly associated with the severity of CHD. Higher TSH level may be a risk factor of CHD.