The IgM Fc receptor (FcμR), the sole receptor specific for IgM, is crucial for B cell survival and humoral immunity. Yet, its role in memory B cells (MBCs) has remained unclear. Here, we show that FcμR-/- mice immunized with the T-dependent antigen 4-hydroxy-3-nitrophenyl acetyl-chicken γ-globulin (NP-CGG) generate normal numbers of IgG1+ MBCs with long-term survival comparable to that of WT mice. However, the IgG1+ MBCs in FcμR-/- mice contained a reduced proportion of mature CD80+PD-L2+ cells, a subset associated with potent recall responses and plasma cell differentiation. Consistently, adoptive transfer of NP-specific MBCs and CGG-specific memory T cells into Rag1-/- mice revealed significantly diminished memory B cell responses in recipients of FcμR-/- MBCs. Mechanistically, FcμR-/- IgG1+ MBCs exhibited impaired B cell receptor signaling and reduced activation of transcription factors essential for plasma cell differentiation upon antigen re-challenge both in vivo and in vitro. Together, these findings establish FcμR as a previously unrecognized key regulator of CD80+PD-L2+ MBC formation and recall responses.

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes, associated with high morbidity, mortality, and healthcare costs. Early detection is challenging due to the lack of highly specific diagnostic tools. This study aimed to develop and validate a nomogram for predicting DKD risk in patients with type 2 diabetes mellitus (T2DM) by integrating conventional biochemical indicators with noninvasive lens advanced glycation end product (AGE) measurements. A total of 868 patients with T2DM from Shanghai Fifth People’s Hospital (November 2019 to February 2024) were enrolled. Independent predictors of DKD were identified using logistic regression and incorporated into a predictive nomogram. Model performance was evaluated using receiver operating characteristic curves, calibration plots, and decision curve analysis. The cutoff value for lens AGE fluorescence (0.306) was derived from our previous study using ROC analysis with Youden’s index. Seven variables were independently associated with DKD: systolic blood pressure, glycated hemoglobin, triglycerides, serum cystatin C, 25-hydroxyvitamin D, red blood cell count, and lens AGE values. The nomogram showed good discrimination, with an AUC of 0.809 in the training cohort and 0.806 in the validation cohort. Calibration demonstrated close agreement between predicted and observed risk, and clinical utility was confirmed. This novel nomogram provides a practical and highly specific tool for early DKD screening and individualized risk assessment in T2DM patients.

Type 1 diabetes(T1D)is defined by autoimmune-mediated destruction of the insulin-producing pancreatic β-cells.Impaired insulin secretion due to β-cell apoptosis and islet mass loss is the main feature of T1D[1].Current therapeutic strategies for T1D are mainly through subcutaneous administration of insulin or islet/pancreas transplantation.However,the ineffectiveness and potential adverse effects on patients drive an urgent need for alter-native therapeutic strategies to improve islet β-cell dysfunction and treat T1D[2].

OBJECTIVE:Women with gestational diabetes mellitus (GDM) often develop a metabolic memory that increases the risk of future metabolic disorders, even after blood glucose levels normalize following clinical intervention. However, the impact of this metabolic memory on susceptibility to SARS-CoV-2 remains unclear. Therefore, we aim to investigate the potential association between metabolic memory in GDM and susceptibility to SARS-CoV-2 infection. METHODS:We conducted a prospective cohort study with 1,675 pregnant women, including 197 (11.8%) with GDM. Postpartum SARS-CoV-2 infections were tracked via telephone follow-up and categorized into negative and positive groups. Logistic regression was used to explore risk factors for SARS-CoV-2 infection. Peripheral blood samples were collected from 30 GDM and 30 normal glucose-tolerant (NGT) pregnant women in three trimesters (T1, T2, T3) for longitudinal untargeted metabolomics to identify GDM and SARS-CoV-2-associated metabolites. Limma package was applied to find differential metabolites (DEMs) associated with SARS-CoV-2 infection and GDM. RESULTS:Among 1,675 women, 1,348 (80.5%) tested positive for SARS-CoV-2. GDM post-partum women had higher SARS-CoV-2 infection rates (88.3% vs. 79.4%, P = 0.003) than NGT women. GDM was associated with SARS-CoV-2 infection (T2: OR [95% CI]: 2.17 [1.26-3.54], P = 0.005; T3: OR [95% CI]: 1.70 [1.03-2.82], P = 0.040). Compared to the SARS-CoV-2 negative group, the positive group exhibited elevated levels of allantoic acid, LPE (0:0/22:6), LPC (15:0/0:0), 1-linoleoyl-sn-glycero-3-phosphorylcholine in T1 and T2, before clinical intervention. In T3, allantoic acid remained elevated post-intervention. A similar increase as described above was observed in the GDM compared to the NGT group. CONCLUSION:Compared to NGT, women with GDM are at a higher risk of postnatal SARS-CoV-2 infection. Metabolic memory from GDM may heighten susceptibility to SARS-CoV-2.

Secretory IgM plays a pivotal role in promoting robust antigen-specific IgG responses, yet the mechanisms underlying its immune-enhancing effects remain incompletely understood. IgM functions through two distinct pathways: engagement of the IgM Fc receptor (FcµR) and activation of the classical complement pathway. However, the extent of redundancy between these pathways and their roles at different stages of B cell differentiation remains unclear. To address this, we utilized FcµR-deficient mice and Cµ13 mice, which express mutant IgM incapable of activating complement. Both strains exhibited impaired T-dependent immune responses to low-dose 4-hydroxy-3-nitrophenyl-chicken γ globulin. Remarkably, FcµR-/-Cµ13 double-mutant mice showed profound defects in antigen-specific IgG production compared with either single mutant, revealing nonredundant, synergistic roles for FcµR and complement. Mechanistically, both pathways are required for early B cell activation and expansion, promoting efficient class switch recombination, germinal center (GC) formation, and plasma cell differentiation. During the GC response, IgM BCR-mediated complement activation, but not FcµR, is required for GC B-cell proliferation, survival, and affinity maturation. In contrast, FcµR primarily enhances BCR signaling in naïve B cells through downstream PI3K-AKT and MAPK pathways. These findings define two cooperative yet distinct IgM-mediated mechanisms that promote humoral immunity and regulate B cell differentiation in vivo.

Renal fibrosis is a major driver of chronic kidney disease (CKD) progression, yet targeted therapies remain limited due to incomplete understanding of key molecular mechanisms. While IL-1-mediated inflammation and mitochondrial dysfunction are recognized contributors, the precise links between IL-1 signaling, fibrosis, and mitochondrial homeostasis are unclear. Here, we investigated the therapeutic effects of recombinant human IL-1 receptor antagonist (rhIL-1Ra) in both acute (UUO) and chronic (5/6Nx) mouse models of kidney injury, as well as in vitro TGF-β1-stimulated kidney cells. rhIL-1Ra significantly attenuated renal fibrosis, inflammation, and functional impairment in vivo. Mechanistically, rhIL-1Ra suppressed TGF-β1-induced expression of the E3 ubiquitin ligase RNF182, which we show mediates MFN2 ubiquitination and degradation, leading to mitochondrial dysfunction. Inhibition of RNF182 by rhIL-1Ra stabilized MFN2, preserved mitochondrial respiration and ATP production, and reduced oxidative stress. Rescue experiments confirmed the centrality of the RNF182-MFN2 axis in fibrotic and mitochondrial injury. Our findings reveal a novel IL-1R/RNF182/MFN2 pathway linking inflammation to mitochondrial and fibrotic pathology, supporting RNF182 as a promising target and rhIL-1Ra as a potential therapy for CKD.

Lupus nephritis (LN) is a leading cause of mortality in systemic lupus erythematosus. While the dominance of Fcγ receptor (FcγR)-activating IgG subclasses has been observed in both human and murine LN, whether this imbalance is causal or merely correlative remains unresolved. To address this, we generated a murine model that exclusively expresses the activating IgG2c while lacking all other IgG subclasses. Despite preserved B cell receptor diversity and intact humoral immunity, these mice developed rapidly progressive and fatal lupus-like nephritis, with 100% mortality by 30 weeks, characterized by extensive renal inflammation. Genetic ablation of FcγRs or complement C3 rescued this phenotype, establishing both as essential and non-redundant mediators of disease. Supporting clinical relevance, renal biopsies from patients with LN exhibited glomerular immune deposits enriched for FcγR-activating IgG1 and minimal inhibitory IgG4. Together, these results identify IgG subclass dominance as a direct driver of LN and provide a fully penetrant, rapid-onset disease model for therapeutic studies.

Dysregulation of matrix metalloproteinase 9 (MMP-9) and chronic low-grade inflammation have been implicated ovulatory dysfunction in polycystic ovary syndrome (PCOS), yet their roles remain inadequately addressed in clinical practice. This study aimed to investigate the interrelationships and functional roles of inflammation, hormone, and the MMP-9/TIMP-1 system in PCOS. A PCOS rat model was established to evaluate serum hormone levels, inflammatory markers, and MMP-9/TIMP-1 levels. Ovarian expression of IL-6 and MMP-9 was examined using Immunohistochemistry and immunofluorescence. Additionally, a cohort study comprising 83 PCOS patients and 97 healthy controls was analyzed to evaluate serum hormonal and inflammatory profiles, with further assessment of their associations with PCOS and predictive value. In the PCOS rat model, marked disruptions in serum lipid and hormone profiles were observed, accompanied by elevated levels of IL-6 and MMP-9. Histological examination of ovarian tissues showed an increased number of atretic follicles and enhanced expression of both IL-6 and MMP-9. In the clinical cohort, patients with PCOS showed significantly higher levels of TSTO, LH and IL-6 compared to controls. Although MMP-9 and TIMP-1 levels were both elevated, the MMP9/TIMP1 ratio remained unchanged. Correlation analysis indicated positive associations between IL-6, TNF-α, MMP-9, TIMP-1, and PCOS. Logistic regression identified TSTO, FSH, and IL-6 as independent risk factors, with ROC analysis further highlighting IL-6 as the most robust predictor for PCOS. This study demonstrates that systemic inflammation and hormonal disturbances are closely linked to PCOS. In PCOS patients, particular attention should be given to elevated levels of inflammatory factors such as IL-6 and dysregulated of the immune microenvironment, which play critical roles in the pathogenesis of the disease. Further exploration of the potential application of targeted inflammatory management in clinical intervention strategies is warranted.

ABSTRACT Background and Aims Renal HMGCS2 upregulation is associated with lipid deposition. However, the expression pattern and role of Hmgcs2 in the perirenal adipose tissue (PRAT) is not clear. This study was designed to elucidate the contribution of Hmgcs2 in the pathogenesis of obese diabetic kidney disease mice. Methods 12‐week‐old db/db (diabetic) and db/m (control) mice were fed high‐fat or normal diets, respectively. At 12, 16, and 20 weeks, mice (n = 4/group/timepoint) were euthanized for metabolic profiling (body weight, blood glucose, urinary ACR) and tissue collection (kidney, PRAT). Tissues were analyzed for TNF‐α mRNA (qPCR), HMGCS2 expression (IHC/WB/IF), lipid deposition (Oil Red O), and histopathology (HE staining). PRAT triglycerides (colorimetric assay) and lipidomics (UPLC–MS/MS) were assessed. HMGCS2‐knockout mice (CRISPR‐generated) underwent metabolic tests (OGTT/ITT) before terminal tissue analysis. Results (1) Compared with db/mPRAT, db/db PRAT had significantly enlarged adipocytes and increased TG content. The expression of HMGCS2 in renal and PRAT was significantly greater in db/db mice. (2) Hmgcs2 was equally expressed in db/db renal and PRAT. PRAT expansion increases the inflammatory factor TNF‐α, which occurs earlier in PRAT than in renal tissue.(3) Genetic ablation of HMGCS2 in mice significantly decreased renal and PRAT TG accumulation, concomitant with attenuated inflammation. (4) LC–MS/MS analysis revealed that TGs are the main PRAT lipid component. Db/db PRAT TG content was significantly greater than that in db/m. Db/db proximal PRAT TG content is greater than that of the distal region, with seven upregulated TG lipid molecules (TG (38:3)+NH4, TG (50:5)+NH4, TG (52:12e)+Na, TG (56:9e)+H, TG (57:6e)+H, FA (18:1)+H, and ST (m45:3)+NH4), among which TG (38:3) has the highest expression. Conclusion Our study strongly suggests that lipids, especially TGs, are deposited in the kidneys and PRAT of DKD mice, with proximal–distal PRAT differences. HMGCS2 may be involved in kidneys and PRAT TG deposition. PRAT‐lipid‐metabolism‐induced inflammation may occur before blood‐glucose‐related kidney damage.

Abstract Perinephric adipose tissue (PRAT) is a component of visceral adipose tissue that is considered an important factor in maintaining renal homeostasis. PRAT has a close relationship with the kidney. Under metabolic dysfunction, PRAT inflammation may precede the damage of blood sugar to the kidney. Whether there is a difference between proximal and distal lipids of PRAT and its significance are not clear. For this reason, we used the nontargeted absolute quantitative method for lipid analysis. The nontargeted analysis method can distinguish various types of lipids in a sample. Absolute quantification of lipids against an internal standard can not only determine the difference in lipid levels between groups but also yield the absolute concentration of lipids in each group. Therefore, we compared the amount and lipid level of PRAT between diabetic kidney disease (DKD) mice and nondiabetic mice and the difference in the lipid spectrum between proximal (within 5 mm from the kidney) and distal (outside 5 mm from the kidney) PRAT in DKD mice. The results showed that DKD mice had significantly more PRAT than the control group. Lipid proteomics found that PRAT in the DKD group significantly differed from that in the control group in glycerides, sphingolipids and phospholipids. Glycerides, including TG (41:10e), TG (43:4), TG (45:7e), TG (52:6) and TG (71:5), were significantly upregulated in PRAT of DKD mice, while TG(56:8e) and TG(55:1) were downregulated. The sphingolipids cer(d36:2), cer(d36:1), cer(d34:2), cer(d34:1) and cerP(t39:3) and the phospholipids PC (38:4), PS (36:4), PS(38:4), PI(42:0), CL(85:1) and CL(76:6) were significantly upregulated in the PRAT of the DKD mice, whereas LPE(16:1e) and PG(41:0) were significantly downregulated. TG(38:3), TG(50:5), TG(52:12e) and TG(56:9e) in the proximal end of PRAT in the DKD group were higher than they were in the distal end, especially TG(38:3), but the sphingolipids and phospholipids in the proximal end of PRAT in the DKD group were downregulated. Our results show that the amount and lipid level of PRAT are significantly higher in DKD mice than non-DKD mice, and there are differences between proximal and distal PRAT. Lipid metabolism in the perirenal fat microenvironment may be related to DKD. These new insights into the mechanism of DKD may be helpful for developing therapeutic strategies for this disease.

This study aimed to assess whether the Haptoglobin (Hp) genotype influences the relationship between hemoglobin (Hb) levels and the development of gestational diabetes mellitus (GDM). Additionally, it sought to evaluate the interaction and joint association of Hb levels and Hp genotype with GDM risk. This retrospective study involved 358 women with GDM and 1324 women with normal glucose tolerance (NGT). Peripheral blood leukocytes were collected from 360 individuals at 14–16 weeks’ gestation for Hp genotyping. GDM was diagnosed between 24–28 weeks’ gestation. Interactive moderating effect, joint analysis, and mediation analysis were performed to evaluate the crosslink of Hb levels and Hp genotype with GDM risk. Women who developed GDM had significantly higher Hb levels throughout pregnancy compared to those with NGT. Increase first-trimester Hb concentration was associated with a progressive rise in GDM incidence, glucose levels, glycosylated hemoglobin levels, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) values, cesarean delivery rates, and composite neonatal outcomes. Spline regression showed a significant linear association of GDM incidence with continuous first-trimester Hb level when the latter exceeded 122 g/L. Increased first-trimester Hb concentration was an independent risk factor for GDM development after adjusting for potential confounding factors in both the overall population and a matched case-control group. The Hp2–2 genotype was more prevalent among pregnant women with GDM when first-trimester Hb exceeded 122 g/L. Significant multiplicative and additive interactions were identified between Hb levels and Hp genotype for GDM risk, adjusted for age and pre-pregnancy BMI. The odds ratio (OR) for GDM development increased incrementally when stratified by Hb levels and Hp genotype. Moreover, first-trimester Hb level partially mediated the association between Hp genotype and GDM risk. Increased first-trimester Hb levels were closely associated with the development of GDM and adverse pregnancy outcomes, with this association moderated by the Hp2–2 genotype.

Our aim was to explore the relationship between serum uric acid (UA) levels in early pregnancy and the development of gestational diabetes mellitus (GDM), and to further explore whether there is a causal relationship. 684 pregnant women with GDM and 1162 pregnant women without GDM participated in this study. 311 pregnant women with GDM and 311 matched controls were enrolled in a 1:1 case-control study. We used conditional logistic regression to explore the relationship between UA levels and the risk of developing GDM. The causal relationship between the two was examined by two-sample Mendelian randomization (MR) analysis. In the 1:1 matched population, the odds ratio (OR) of developing GDM compared with the extreme tertiles of UA levels was 1.967 (95

Background Advanced glycation end products (AGEs) deposited in the lens are correlated with those in the kidneys, indicating a possible value in evaluating diabetic kidney disease (DKD). This study explored the value of noninvasively measuring lens AGEs to diagnose and evaluate the severity of diabetic nephropathy in patients with type 2 diabetes mellitus (T2DM). Methodology A total of 134 T2DM patients admitted to the Fifth People's Hospital of Shanghai from March 2020 to May 2021 were selected randomly. Patients were divided into low-, medium-and high-risk groups according to the risk assessment criteria for DKD progression and into DKD and non-DKD (non-DKD) groups according to the Guidelines for the Prevention and Treatment of Diabetic Nephropathy in China. The concentrations of noninvasive AGEs in the lens in all the groups were retrospectively analyzed. Results The concentration of noninvasive lens AGEs in the high-risk patients, according to the 2012 guidelines of the Global Organization for Improving the Prognosis of Kidney Diseases, was significantly higher than that in the remaining groups. Regression analysis suggested the value of lens AGEs in diagnosing DKD and evaluating DKD severity. Cox regression analysis indicated that the noninvasive lens AGE concentration was positive correlated with the course of disease. Conclusion The receiver operating characteristic (ROC) curve suggested that using noninvasive lens AGE measurements has clinical value in the diagnosis of DKD (area under the curve 62.4%,95% confidence interval (CI) 52.4%–73.9%, p = 0.014) and in assessing the severity of DKD (area under the curve 83.2%, 95% CI 74.1%–92.3%, P < 0.001). Noninvasive lens AGE testing helps screen T2DM patients for DKD and evaluate the severity of DKD.

Insertions and deletions (indels) are low-frequency deleterious genomic DNA alterations. Despite their rarity, indels are common, and insertions leading to long complementarity-determining region 3 (CDR3) are vital for antigen-binding functions in broadly neutralizing and polyreactive antibodies targeting viruses. Because of challenges in detecting indels, the mechanism that generates indels during immunoglobulin diversification processes remains poorly understood. We carried out ultra-deep profiling of indels and systematically dissected the underlying mechanisms using passenger-immunoglobulin mouse models. We found that activation-induced cytidine deaminase-dependent ±1-base pair (bp) indels are the most prevalent indel events, biasing deleterious outcomes, whereas longer in-frame indels, especially insertions that can extend the CDR3 length, are rare outcomes. The ±1-bp indels are channeled by base excision repair, but longer indels require additional DNA-processing factors. Ectopic expression of a DNA exonuclease or perturbation of the balance of DNA polymerases can increase the frequency of longer indels, thus paving the way for models that can generate antibodies with long CDR3. Our study reveals the mechanisms that generate beneficial and deleterious indels during the process of antibody somatic hypermutation and has implications in understanding the detrimental genomic alterations in various conditions, including tumorigenesis.

Non-alcoholic steatohepatitis (NASH) is a major contributor to liver cirrhosis and hepatocellular carcinoma. There remains no effective pharmacological therapy. The hepatic lipid metabolism and fatty acid β-oxidation are regulated by Perilipin5 (Plin5). However, it is yet unknown how Plin5 affects NASH and the molecular process. High-fat, high-cholesterol and high-fructose (HFHC) diets were used to mimic the progression of NASH in wild type (WT) mice and Plin5 knockout (Plin5 KO) mice. The degree of ferroptosis was measured by detecting the expression of key genes of ferroptosis and the level of lipid peroxide. The degree of NASH was judged by observing the morphology of the liver, detecting the expression of inflammation and fibrosis related genes of liver damage. Plin5 was overexpressed in the liver of mice by tail vein injection of adenovirus, and the process of NASH was simulated by methionine choline deficiency (MCD) diet. The occurrence of ferroptosis and NASH was detected by the same detection method. Targeted lipidomics sequencing was used to detect the difference in free fatty acid expression in the WT Plin5 KO group. Finally, it was verified in cell experiments to further study the effect of free fatty acids on ferroptosis of hepatocytes. In various NASH models, hepatic Plin5 was dramatically reduced. Plin5 knockout (KO) worsened NASH-associated characteristics in mice given a high-fat/high-cholesterol (HFHC) diet, such as lipid accumulation, inflammation and hepatic fibrosis. It has been shown that ferroptosis is involved in NASH progression. We revealed that Plin5 KO in mice aggravated the degree of ferroptosis in NASH models. Conversely, overexpression of Plin5 significantly alleviated ferroptosis and further ameliorated progression of MCD-induced NASH. Analysis of livers obtained from HFHC diet-fed mice by targeted lipidomics revealed that 11-Dodecenoic acid was significantly decreased in Plin5 KO mice. Addition of 11-Dodecenoia acid to Plin5 knockdown hepatocytes effectively prevented ferroptosis. Our study demonstrates that Plin5 protects against NASH progression by increasing 11-Dodecenoic acid level and further inhibiting ferroptosis, suggesting that Plin5 has therapeutic potential as a target for the management of NASH.

Objective Neutropenia is a complication of Graves' disease (GD), but there is currently no means by which to predict its occurrence. This study aimed to investigate the risk factors for the development of neutropenia in untreated GD. Methods This was a retrospective cohort study. Between January 1, 2010, and July 31, 2020, 1000 patients with new-onset or relapsing GD without treatment were enrolled in the study and divided into two groups: neutropenia group (neutrophil count < 2 × 109/L) and non-neutropenia group (neutrophil count ≥ 2 × 109/L). Clinical characteristics of subjects were compared between the two groups, and logistic regression analysis was applied to determine risk factors for neutropenia. To further explore the correlation of radioactive iodine uptake (RAIU) with neutropenia, subjects were first classified according to quartile of 3 h RAIU and 24 h RAIU prior to logistic regression analysis. Results Of all patients recruited, 293 (29.6%) were diagnosed with neutropenia. Compared with non-neutropenic patients, those with neutropenia had a higher level of free thyroxine (FT4) (56.64 ± 31.80 vs 47.64 ± 39.64, P = 0.001), 3 h RAIU (55.64 ± 17.04 vs 49.80 ± 17.21, P < 0.001) and 24 h RAIU (67.38 ± 12.54 vs 64.38 ± 13.58, P < 0.001). Univariate logistic regression analysis revealed that FT4, 3 h RAIU, 24 h RAIU, creatinine, and low-density lipoprotein were risk factors for development of neutropenia in GD. After adjusting for confounding factors of age, BMI, and sex, we determined that 3 h RAIU and 24 h RAIU (Model 1: OR = 1.021, 95% CI: 1.008–1.033, P = 0.001; Model 2: OR = 1.023, 95% CI: 1.007–1.039, P = 0.004), but not FT4, were associated with the development of neutropenia. Conclusions RAIU is associated with neutropenia in patients with untreated GD.

目的 探讨胎盘SLC16A1基因及单羧酸转运蛋白1(MCT1)表达量与妊娠期糖尿病(GDM)的关系.方法 选取该院1 361例妊娠女性为研究对象,其中GDM患者281例纳入GDM组,健康妊娠女性1 080例纳入正常妊娠组.正常妊娠组及GDM 组按1 ∶1匹配(n=105)后比较两组胎盘 MCT1及SLC16A1基因表达量,并采用Logistic回归分析MCT1及SLC16A1基因表达量与GDM的关系.匹配参数为体质量指数、年龄、生产史、GDM病史(匹配容差分别为0.3、0、0、0).结果 GDM组、正常妊娠组SLC16A1基因表达量分别为0.390(0.006,2.980)、0.561(0.014,4.205),GDM组明显低于正常妊娠组,差异有统计学意义(P＜0.05).GDM组、正常妊娠组MCT1表达量分别为0.097±0.044、0.166±0.030,GDM组明显低于正常妊娠组,差异有统计学意义(P＜0.05).Logistic回归分析显示SLC16A1基因表达量增加是GDM的保护因素(OR=0.740,95％CI 0.561～0.974,P＜0.05).结论 GDM 患者胎盘 SLC16A1 基因及 MCT1 表达量均下降,SLC16A1基因表达量增加是GDM的保护因素.

Objective To explore the relationship between estradiol (E2) and thyroid function during the second trimester of pregnancy and the effect of E2 on sodium iodide transporter (NIS) expression in cultured thyroid cells. Materials and methods We analyzed relationships between E2 and thyroid function in 196 pregnant women during the second trimester. Multiple linear regression analysis was performed between E2 and thyroid function. The human thyroid Nthy-ori3-1 cells were cultured in different E2 concentrations, and the mRNA levels of NIS, estrogen receptor (ER)-α, and ER-β were measured by quantitative real-time PCR. Their protein levels were assessed by western blot. Results E2 was positively correlated with thyroid-stimulating hormone (TSH) and negatively correlated with free thyroxine (FT4) (P < 0.05). When we corrected for age, BMI, alanine aminotransferase, and serum creatinine, E2 was still negatively correlated with FT4 (P < 0.5) during the second trimester. In Nthy-ori3-1 cells treated with 10 nM E2, NIS and ER-β mRNA levels were significantly reduced, while ER-α mRNA level was not altered (P > 0.5). Moreover, 10 nM E2 significantly decreased protein levels of ER-β, phosphorylated versions of protein kinase A (p-PKA), phosphorylated versions of cAMP response element-binding protein (p-CREB), and NIS, while treatment with the ER-β inhibitor restored the expression of p-PKA, p-CREB, and NIS (P < 0.05). Conclusion High concentration of E2 has a negative correlation with FT4. High concentration of E2 can inhibit the NIS expression through the ER-β-mediated pathway, which may cause thyroid hormone fluctuations during pregnancy.