Nodule Development Research Articles

Overexpression of the MtCLE35 gene in transgenic Medicago truncatula plants inhibits nodulation at early stages of symbiosis development

CLE (CLAVATA3/ENDOSPERM SURROUNDING REGION-related) peptides are known as systemic regulators of legume-rhizobium symbiosis that negatively control the number of nitrogen-fixing nodules. These regulatory peptides are produced in the root in response to inoculation with rhizobia, and are transported through the xylem to the shoot, where they are recognized by their receptor, CLV1-like (CLAVATA1-like) kinase, active in leaf phloem cells. After that, a shoot-derived signaling pathway is activated that inhibits subsequent nodule development in the root. Previously, we found that in Medicago truncatula, the expression of the MtCLE35 gene is activated in response to rhizobia and nitrate treatment, and its overexpression systemically inhibits nodulation. However, little is known about the downstream target genes regulated by a MtCLE35 signaling pathway in the root. Moreover, it is not completely clear which stage of symbiosis development is affected by MtCLE35-activated pathway. In order to identify genes regulated by the MtCLE35-induced signaling pathway, we performed a transcriptomic analysis of the roots overexpressing the MtCLE35 gene. Totally, 1122 genes were found to be differentially expressed between MtCLE35-overexpressing and control roots after rhizobial inoculation, among them 185 genes were upregulated and 937 genes were downregulated. Among downregulated genes, many known regulators of legume-rhizobia symbiosis were found. In addition to this, we analyze early steps of interaction between M. truncatula overexpressing the MtCLE35 gene and Sinorhizobium meliloti labeled with fluorescent reporter. We did not observe penetration of S. meliloti into host plant roots with MtCLE35 overexpression. Our data suggest that overexpression of the MtCLE35 gene inhibits nodulation at the very early stages of symbiosis development.

Effects of Elevated Temperature on Pisum sativum Nodule Development: II-Phytohormonal Responses.

High temperature is one of the most important factors limiting legume productivity. We have previously shown the induction of senescence in the apical part of nodules of the pea SGE line, formed by Rhizobium leguminosarum bv. viciae strain 3841, when they were exposed to elevated temperature (28 °C). In this study, we analyzed the potential involvement of abscisic acid (ABA), ethylene, and gibberellins in apical senescence in pea nodules under elevated temperature. Immunolocalization revealed an increase in ABA and 1-aminocyclopropane-1-carboxylic acid (ACC, the precursor of ethylene biosynthesis) levels in cells of the nitrogen fixation zone in heat-stressed nodules in 1 day of exposure compared to heat-unstressed nodules. Both ABA and ethylene appear to be involved in the earliest responses of nodules to heat stress. A decrease in the gibberellic acid (GA3) level in heat-stressed nodules was observed. Exogenous GA3 treatment induced a delay in the degradation of the nitrogen fixation zone in heat-stressed nodules. At the same time, a decrease in the expression level of many genes associated with nodule senescence, heat shock, and defense responses in pea nodules treated with GA3 at an elevated temperature was detected. Therefore, apical senescence in heat-stressed nodules is regulated by phytohormones in a manner similar to natural senescence. Gibberellins can be considered as negative regulators, while ABA and ethylene can be considered positive regulators.

Thyroid tuberculosis associated with papillary microcarcinoma: case report and review of literature

Introduction: Thyroid tuberculosis (TB) is extremely rare. Infection may first occur in the thyroid gland or may be secondary to TB in other parts of the body. The diagnosis is rarely made clinically because the disease’s variable presentation often resembles that of a malignancy or an euthyroid nodular goiter. Case report: We present the case of a 40-year-old woman, who presented multiple thyroid nodules in both lobes. Two of these nodules were classified as EU-TIRADS V (European Thyroid Imaging and Reporting Data System). The ultrasound also found an adenopathy of the inferior part of the jugular lymphatic chain, in favor of malignancy. The histopathological examination after total thyroidectomy showed thyroid TB, associated to a papillary microcarcinoma of the right thyroid lobe, and the final examination of the adenopathy showed similar granulomas with caseous necrosis, and no signs of metastasis. Clinical discussion: Thyroid TB is very rare. Its diagnosis is difficult due to a lack of specific signs and symptoms, which is why the diagnosis is most commonly made on pathological examination after thyroid surgery. It is well known that mycobacterial infection creates an environment of chronic and persistent inflammation, with possible DNA damage. This can create a microenvironment that is highly conductive to carcinogenesis, which could explain the discovery of papillary microcarcinoma in addition to thyroid TB in our patient. Conclusion: This report presents a rare case of malicious growth development of thyroid nodules and thyroid TB. Therefore, physicians must always be vigilant when managing thyroid nodules, as there is always the possibility of malignant lesions associated to an inflammatory or infectious cause.

Treated Non Seminomatous Germ Cell Tumor of Testes Post Resection of Teratomatous Lung Nodule

Background: Testicular tumors are relatively rare, accounting for only 1% of all malignancies in men. Among the different types of testicular tumors, germ cell tumors are the most common. They are very sensitive to chemotherapy and are curable even when metastatic. Cure rates approximates 90%-95% in good risk and early stage tumors. Earlier on, metastatic testicular cancer was usually incurable and fatal, but newer treatments including high-dose chemotherapy and stem cell rescue have changed the scenario. Case Presentation: This case report presents a case of a 30-year-old male with a large testicular tumor, diagnosed as a mixed germ cell tumor consisting of a yolk sac tumor, teratoma with immature elements, and seminoma with germ cell neoplasia in situ. After undergoing radical orchiectomy, the patient experienced a postoperative decline in alpha-fetoprotein levels and was placed on surveillance. Subsequent imaging revealed the development of a lung nodule, accompanied by an increase in alpha-fetoprotein levels. The patient received chemotherapy with three cycles of BEP (bleomycin, etoposide, platinum), resulting in a partial response. Due to the patient's COVID-19 infection, the final cycle of chemotherapy was modified. Further imaging showed a marginal decrease in the size of the lung nodule, prompting surgical resection. The lung nodule was found to be a post-pubertal teratoma without significant immature elements. Following surgery, the patient's alpha-fetoprotein levels decreased to a baseline nadir. Close follow-up continues, demonstrating no evidence of disease recurrence. Conclusion: This case emphasizes the importance of a multidisciplinary approach, including surgery and chemotherapy, in managing testicular germ cell tumors with metastasis, leading to favorable outcomes and long-term disease control.

The nitrate transporter-sensor MtNPF6.8 regulates the branched chain amino acid/pantothenate metabolic pathway in barrel medic (Medicago truncatula Gaertn.) root tip

Nitrogen is the most limiting nutrient for plants, and it is preferentially absorbed in the form of nitrate by roots, which adapt to nitrate fluctuations by remodelling their architecture. Although core mechanisms of the response to nitrate availability are relatively well-known, signalling events controlling root growth and architecture have not all been identified, in particular in Legumes. However, the developmental effect of nitrate in Legumes is critical since external nitrate not only regulates root architecture but also N2-fixing nodule development. We have previously shown that in barrel medic (Medicago truncatula), the nitrate transporter MtNPF6.8 is required for nitrate sensitivity in root tip. However, uncertainty remains as to whether nitrogen metabolism itself is involved in the MtNPF6.8-mediated response. Here, we examine the metabolic effects of MtNPF6.8-dependent nitrate signalling using metabolomics and proteomics in WT and mtnpf6.8 root tips in presence or absence of nitrate. We found a reorchestration of metabolism due to the mutation, in favour of the branched chain amino acids/pantothenate metabolic pathway, and lipid catabolism via glyoxylate. That is, the mtnpf6.8 mutation was likely associated with a specific rerouting of acetyl-CoA production (glyoxylic cycle) and utilisation (pantothenate and branched chain amino acid synthesis). In agreement with our previous findings, class III peroxidases were confirmed as the main protein class responsive to nitrate, although in an MtNPF6.8-independent fashion. Our data rather suggest the involvement of other pathways within mtnpf6.8 root tips, such as Ca2+ signalling or cell wall methylation.

Localized osmotic stress activates systemic responses to N limitation in Medicago truncatula-Sinorhizobium symbiotic plants.

In mature symbiotic root nodules, differentiated rhizobia fix atmospheric dinitrogen and provide ammonium to fulfill the plant nitrogen (N) demand. The plant enables this process by providing photosynthates to the nodules. The symbiosis is adjusted to the whole plant N demand thanks to systemic N signaling controlling nodule development. Symbiotic plants under N deficit stimulate nodule expansion and activate nodule senescence under N satiety. Besides, nodules are highly sensitive to drought. Here, we used split-root systems to characterize the systemic responses of symbiotic plants to a localized osmotic stress. We showed that polyéthylène glycol (PEG) application rapidly inhibited the symbiotic dinitrogen fixation activity of nodules locally exposed to the treatment, resulting to the N limitation of the plant supplied exclusively by symbiotic dinitrogen fixation. The localized PEG treatment triggered systemic signaling stimulating nodule development in the distant untreated roots. This response was associated with an enhancement of the sucrose allocation. Our analyses showed that transcriptomic reprogramming associated with PEG and N deficit systemic signaling(s) shared many targets transcripts. Altogether, our study suggests that systemic N signaling is a component of the adaptation of the symbiotic plant to the local variations of its edaphic environment.

Dynamics of hemoglobins during nodule development, nitrate response, and dark stress in Lotus japonicus.

Legume nodules express multiple leghemoglobins (Lbs) and non-symbiotic hemoglobins (Glbs), but how they are regulated is unclear. Here, we study the regulation of all Lbs and Glbs of Lotus japonicus in different physiologically relevant conditions and mutant backgrounds. We quantified hemoglobin expression, localized reactive oxygen species (ROS) and nitric oxide (NO) in nodules, and deployed mutants deficient in Lbs and in the transcription factors NLP4 (associated with nitrate sensitivity) and NAC094 (associated with senescence). Expression of Lbs and class 2 Glbs was suppressed by nitrate, whereas expression of class 1 and 3 Glbs was positively correlated with external nitrate concentrations. Nitrate-responsive elements were found in the promoters of several hemoglobin genes. Mutant nodules without Lbs showed accumulation of ROS and NO and alterations of antioxidants and senescence markers. NO accumulation occurred by a nitrate-independent pathway, probably due to the virtual disappearance of Glb1-1 and the deficiency of Lbs. We conclude that hemoglobins are regulated in a gene-specific manner during nodule development and in response to nitrate and dark stress. Mutant analyses reveal that nodules lacking Lbs experience nitro-oxidative stress and that there is compensation of expression between Lb1 and Lb2. They also show modulation of hemoglobin expression by NLP4 and NAC094.

Persulfidation of plant and bacteroid proteins is involved in legume nodule development and senescence.

Legumes establish symbiosis with rhizobia, forming nitrogen-fixing nodules. The central role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in nodule biology has been clearly established. Recently, hydrogen sulfide (H2S) and other reactive sulfur species (RSS) have emerged as novel signaling molecules in animals and plants. A major mechanism by which ROS, RNS, and RSS fulfil their signaling role is the post-translational modification of proteins. To identify possible functions of H2S in nodule development and senescence, we used the tag-switch method to quantify changes in the persulfidation profile of common bean (Phaseolus vulgaris) nodules at different developmental stages. Proteomic analyses indicate that persulfidation plays a regulatory role in plant and bacteroid metabolism and senescence. The effect of a H2S donor on nodule functioning and on several proteins involved in ROS and RNS homeostasis was also investigated. Our results using recombinant proteins and nodulated plants support a crosstalk among H2S, ROS, and RNS, a protective function of persulfidation on redox-sensitive enzymes, and a beneficial effect of H2S on symbiotic nitrogen fixation. We conclude that the general decrease of persulfidation levels observed in plant proteins of aging nodules is one of the mechanisms that disrupt redox homeostasis leading to senescence.

Characteristics of glucose change in diabetes mellitus generalized through continuous wavelet transform processing: A preliminary study.

The continuous glucose monitoring (CGM) system has become a popular evaluation tool for glucose fluctuation, providing a detailed description of glucose change patterns. We hypothesized that glucose fluctuations may contain specific information on differences in glucose change between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), despite similarities in change patterns, because of different etiologies. Unlike Fourier transform, continuous wavelet transform (CWT) is able to simultaneously analyze the time and fre-quency domains of oscillating data. To investigate whether CWT can detect glucose fluctuations in T1DM. The 60-d and 296-d glucose fluctuation data of patients with T1DM (n = 5) and T2DM (n = 25) were evaluated respectively. Glucose data obtained every 15 min for 356 d were analyzed. Data were assessed by CWT with Morlet form (n = 7) as the mother wavelet. This methodology was employed to search for limited frequency glucose fluctuation in the daily glucose change. The frequency and enclosed area (0.02625 scalogram value) of 18 emerged signals were compared. The specificity for T1DM was evaluated through multiple regression analysis using items that demonstrated significant differences between them as explanatory variables. The high frequency at midnight (median: 75 Hz, cycle time: 19 min) and middle frequency at noon (median: 45.5 Hz, cycle time: 32 min) were higher in T1DM vs T2DM (median: 73 and 44 Hz; P = 0.006 and 0.005, respectively). The area of the > 100 Hz zone at midnight to forenoon was more frequent and larger in T1DM vs T2DM. In a day, the lower frequency zone (15-35 Hz) was more frequent and the area was larger in T2DM than in T1DM. The three-dimensional scatter diagrams, which consist of the time of day, frequency, and area of each signal after CWT, revealed that high frequency signals belonging to T1DM at midnight had a loose distribution of wave cycles that were 17-24 min. Multivariate analysis revealed that the high frequency signal at midnight could characterize T1DM (odds ratio: 1.33, 95% confidence interval: 1.08-1.62; P = 0.006). CWT might be a novel tool for differentiate glucose fluctuation of each type of diabetes mellitus using CGM data.

Analysis of influencing factors and interaction of body weight and disease outcome in patients with prediabetes.

The trend of prediabetes progressing to type 2 diabetes mellitus (T2DM) is prominent, and effective intervention can lead to a return to prediabetes. Exploring the factors influencing the outcome of prediabetes is helpful to guide clinical intervention. The weight change in patients with prediabetes has not attracted much attention. To explore the interaction between body weight and the factors affecting the progression of prediabetes to T2DM. We performed a retrospective analysis of 236 patients with prediabetes and 50 with normal glucose tolerance (NGT), and collected clinical data and follow-up results of all patients. Based on natural blood glucose outcomes, we classified 66 patients with progression to T2DM into the disease progression (DP) group, and 170 patients without progression to T2DM into the disease outcome (DO) group. We analyzed the factors that influenced prediabetes outcome and the influence of body weight on prediabetes blood glucose outcome by unconditional logistic regression. A general linear model (univariate) was used to analyze the inter-action between body weight and independent influencing factors. There were 98 cases of impaired fasting glucose (IFG), 90 cases of impaired glucose tolerance (IGT), and 48 cases of coexistent IFG and IGT. The body weight, waist circumference, body mass index, fasting blood glucose, and 2 h plasma glucose of patients with IFG, IGT, and coexistent IFG and IGT were higher than those in patients with NGT (P < 0.05). Logistic regression analysis showed that body weight, glycosylated hemoglobin, uric acid, fasting insulin, and homeostatic model assessment for insulin resistance were independent factors affecting progression of prediabetes to T2DM (P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve predicted by the above indicators combined was 0.905 [95% confidence interval (CI): 0.863-0.948], which was greater than that predicted by each indicator alone. Logistic regression analysis with baseline body weight as an independent variable showed that compared with body weight 1, the odds ratio (95%CI) of body weight 3 was 1.399 (1.142-2.126) (P = 0.033). There was a multiplicative interaction between body weight and uric acid (β = 1.953, P = 0.005). High body weight in patients with prediabetes is an independent risk factor for progression to T2DM, and the risk of progression is increased when coexisting with high uric acid level.

Accessibility and utilization of healthcare services among diabetic patients: Is diabetes a poor man's ailment?

Diabetes is a non-communicable ailment that has adverse effects on the individual's overall well-being and productivity in society. The main objective of this study was to examine the empirical literature concerning the association between diabetes and poverty and the accessibility and utilization of medical care services among diabetic patients. The diabetes literature was explored using a literature review approach. This review revealed that diabetes is an ailment that affects all individuals irrespective of socioeconomic status; however, its pre-valence is high in low-income countries. Hence, despite the higher prevalence of diabetes in developing countries compared with developed countries, diabetes is not a poor man's ailment because it affects individuals of all incomes. While the number of diabetic patients that access and utilize diabetes medical care services has increased over the years, some personal and institutional factors still limit patients' access to the use of diabetes care. Also, there is a lacuna in the diabetes literature concerning the extent of utilization of available healthcare services by diabetic patients.

Effect of individualized nutrition interventions on clinical outcomes of pregnant women with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) can lead to excessive pregnancy weight gain (PWG), abnormal glucolipid metabolism, and delayed lactation. Therefore, it is necessary to provide appropriate and effective interventions for pregnant women with GDM. To clarify the effects of individualized nutrition interventions on PWG, glucolipid metabolism, and lactation in pregnant women with GDM. The study population consisted of 410 pregnant women with GDM who received treatment at the Northern Jiangsu People's Hospital of Jiangsu Province and Yangzhou Maternal and Child Health Hospital between December 2020 and December 2022, including 200 who received routine in-terventions [control (Con) group] and 210 who received individualized nutrition interventions [research (Res) group]. Data on PWG, glucolipid metabolism [total cholesterol, (TC); triglycerides (TGs); fasting blood glucose (FPG); glycosylated hemoglobin (HbA1c)], lactation time, perinatal complications (cesarean section, premature rupture of membranes, postpartum hemorrhage, and pregnancy-induced hypertension), and neonatal adverse events (premature infants, fetal macrosomia, hypo-glycemia, and respiratory distress syndrome) were collected for comparative analysis. The data revealed markedly lower PWG in the Res group vs the Con group, as well as markedly reduced TG, TC, FPG and HbA1c levels after the intervention that were lower than those in the Con group. In addition, obviously earlier lactation and statistically lower incidences of perinatal complications and neonatal adverse events were observed in the Res group. Individualized nutrition interventions can reduce PWG in pregnant women with GDM, improve their glucolipid metabolism, and promote early lactation, which deserves clinical promotion.

Effects of insulin aspart and metformin on gestational diabetes mellitus and inflammatory markers

Diabetes mellitus is one of the most common causes of chronic kidney disease. Kidney involvement in patients with diabetes has a wide spectrum of clinical presentations ranging from asymptomatic to overt proteinuria and kidney failure. The development of kidney disease in diabetes is associated with structural changes in multiple kidney compartments, such as the vascular system and glomeruli. Glomerular alterations include thickening of the glomerular basement membrane, loss of podocytes, and segmental mesangiolysis, which may lead to microaneurysms and the development of pathognomonic Kimmelstiel-Wilson nodules. Beyond lesions directly related to diabetes, awareness of the possible coexistence of nondiabetic kidney disease in patients with diabetes is increasing. These nondiabetic lesions include focal segmental glomerulosclerosis, IgA nephropathy, and other primary or secondary renal disorders. Differential diagnosis of these conditions is crucial in guiding clinical management and therapeutic approaches. However, the relationship between diabetes and the kidney is bidirectional; thus, new-onset diabetes may also occur as a complication of the treatment in patients with renal diseases. Here, we review the complex and multifaceted correlation between diabetes and kidney diseases and discuss clinical presentation and course, differential diagnosis, and therapeutic opportunities offered by novel drugs.

Multifaceted relationship between diabetes and kidney diseases: Beyond diabetes.

Diabetes mellitus is one of the most common causes of chronic kidney disease. Kidney involvement in patients with diabetes has a wide spectrum of clinical presentations ranging from asymptomatic to overt proteinuria and kidney failure. The development of kidney disease in diabetes is associated with structural changes in multiple kidney compartments, such as the vascular system and glomeruli. Glomerular alterations include thickening of the glomerular basement membrane, loss of podocytes, and segmental mesangiolysis, which may lead to microaneurysms and the development of pathognomonic Kimmelstiel-Wilson nodules. Beyond lesions directly related to diabetes, awareness of the possible coexistence of nondiabetic kidney disease in patients with diabetes is increasing. These nondiabetic lesions include focal segmental glomerulosclerosis, IgA nephropathy, and other primary or secondary renal disorders. Differential diagnosis of these conditions is crucial in guiding clinical management and therapeutic approaches. However, the relationship between diabetes and the kidney is bidirectional; thus, new-onset diabetes may also occur as a complication of the treatment in patients with renal diseases. Here, we review the complex and multifaceted correlation between diabetes and kidney diseases and discuss clinical presentation and course, differential diagnosis, and therapeutic oppor-tunities offered by novel drugs.

Gut microbiome supplementation as therapy for metabolic syndrome.

The gut microbiome is defined as an ecological community of commensal symbiotic and pathogenic microorganisms that exist in our body. Gut microbiome dysbiosis is a condition of dysregulated and disrupted intestinal bacterial homeostasis, and recent evidence has shown that dysbiosis is related to chronic inflammation, insulin resistance, cardiovascular diseases (CVD), type 2 diabetes mellitus (T2DM), and obesity. It is well known that obesity, T2DM and CVD are caused or worsened by multiple factors like genetic predisposition, environmental factors, unhealthy high calorie diets, and sedentary lifestyle. However, recent evidence from human and mouse models suggest that the gut microbiome is also an active player in the modulation of metabolic syndrome, a set of risk factors including obesity, hyperglycemia, and dyslipidemia that increase the risk for CVD, T2DM, and other diseases. Current research aims to identify treatments to increase the number of beneficial microbiota in the gut microbiome in order to modulate metabolic syndrome by reducing chronic inflammation and insulin resistance. There is increasing interest in supplements, classified as prebiotics, probiotics, synbiotics, or postbiotics, and their effect on the gut microbiome and metabolic syndrome. In this review article, we have summarized current research on these supplements that are available to improve the abundance of beneficial gut microbiota and to reduce the harmful ones in patients with metabolic syndrome.

Partners in diabetes epidemic: A global perspective.

There is a recent increase in the worldwide prevalence of both obesity and diabetes. In this review we assessed insulin signaling, genetics, environment, lipid metabolism dysfunction and mitochondria as the major determinants in diabetes and to identify the potential mechanism of gut microbiota in diabetes diseases. We searched relevant articles, which have key information from laboratory experiments, epidemiological evidence, clinical trials, experimental models, meta-analysis and review articles, in PubMed, MEDLINE, EMBASE, Google scholars and Cochrane Controlled Trial Database. We selected 144 full-length articles that met our inclusion and exclusion criteria for complete assessment. We have briefly discussed these associations, challenges, and the need for further research to manage and treat diabetes more efficiently. Diabetes involves the complex network of physiological dysfunction that can be attributed to insulin signaling, genetics, environment, obesity, mitochondria and stress. In recent years, there are intriguing findings regarding gut microbiome as the important regulator of diabetes. Valid approaches are necessary for speeding medical advances but we should find a solution sooner given the burden of the metabolic disorder - What we need is a collaborative venture that may involve laboratories both in academia and industries for the scientific progress and its application for the diabetes control.

Establishment and evaluation of a risk prediction model for gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a condition characterized by high blood sugar levels during pregnancy. The prevalence of GDM is on the rise globally, and this trend is particularly evident in China, which has emerged as a significant issue impacting the well-being of expectant mothers and their fetuses. Identifying and addressing GDM in a timely manner is crucial for maintaining the health of both expectant mothers and their developing fetuses. Therefore, this study aims to establish a risk prediction model for GDM and explore the effects of serum ferritin, blood glucose, and body mass index (BMI) on the occurrence of GDM. To develop a risk prediction model to analyze factors leading to GDM, and evaluate its efficiency for early prevention. The clinical data of 406 pregnant women who underwent routine prenatal examination in Fujian Maternity and Child Health Hospital from April 2020 to December 2022 were retrospectively analyzed. According to whether GDM occurred, they were divided into two groups to analyze the related factors affecting GDM. Then, according to the weight of the relevant risk factors, the training set and the verification set were divided at a ratio of 7:3. Subsequently, a risk prediction model was established using logistic regression and random forest models, and the model was evaluated and verified. Pre-pregnancy BMI, previous history of GDM or macrosomia, hypertension, hemoglobin (Hb) level, triglyceride level, family history of diabetes, serum ferritin, and fasting blood glucose levels during early pregnancy were de-termined. These factors were found to have a significant impact on the development of GDM (P < 0.05). According to the nomogram model's prediction of GDM in pregnancy, the area under the curve (AUC) was determined to be 0.883 [95% confidence interval (CI): 0.846-0.921], and the sensitivity and specificity were 74.1% and 87.6%, respectively. The top five variables in the random forest model for predicting the occurrence of GDM were serum ferritin, fasting blood glucose in early pregnancy, pre-pregnancy BMI, Hb level and triglyceride level. The random forest model achieved an AUC of 0.950 (95%CI: 0.927-0.973), the sensitivity was 84.8%, and the specificity was 91.4%. The Delong test showed that the AUC value of the random forest model was higher than that of the decision tree model (P < 0.05). The random forest model is superior to the nomogram model in predicting the risk of GDM. This method is helpful for early diagnosis and appropriate intervention of GDM.

Role of glycolysis in diabetic atherosclerosis.

Diabetes mellitus is a kind of typical metabolic disorder characterized by elevated blood sugar levels. Atherosclerosis (AS) is one of the most common complications of diabetes. Modern lifestyles and trends that promote overconsumption and unhealthy practices have contributed to an increase in the annual incidence of diabetic AS worldwide, which has created a heavy burden on society. Several studies have shown the significant effects of glycolysis-related changes on the occurrence and development of diabetic AS, which may serve as novel thera-peutic targets for diabetic AS in the future. Glycolysis is an important metabolic pathway that generates energy in various cells of the blood vessel wall. In particular, it plays a vital role in the physiological and pathological activities of the three important cells, Endothelial cells, macrophages and vascular smooth muscle cells. There are lots of similar mechanisms underlying diabetic and common AS, the former is more complex. In this article, we describe the role and mechanism underlying glycolysis in diabetic AS, as well as the therapeutic targets, such as trained immunity, microRNAs, gut microbiota, and associated drugs, with the aim to provide some new perspectives and potentially feasible programs for the treatment of diabetic AS in the foreseeable future.

Cutaneous Manifestations of Rheumatoid Arthritis: Diagnosis and Treatment.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder characterized by inflammatory arthritis and periarticular structural damage. Available evidence suggests that RA results from complex interactions between genetic susceptibility (e.g., HLA-DRB1), environmental factors (e.g., smoking), and immune dysregulation. Alongside joint-related symptoms, individuals with RA may also experience a wide array of skin issues, including the development of nodules, neutrophilic dermatoses, vasculitis, and vasculopathy. Treatment strategies for these manifestations vary but routinely involve corticosteroids, disease-modifying anti-rheumatic drugs, and biologics, with individualized approaches guided by disease severity. In this review, we provide comprehensive insights into the skin-related issues associated with RA, outlining their clinical characteristics and histopathological findings. Our aim is to facilitate early diagnosis and personalized treatment to improve the quality of life of affected individuals.

SAT491 Development of Thyroidal Nodule in Congenital Hypothyroid Girl With Thyroid Peroxidase Gene Mutation

Abstract Disclosure: J. Lee: None. A. Oh: None. H. Han: None. Background: Reduced thyroxine synthesis in dyshormonogenesis induces increased thyrotropin (TSH) secretion through reduced negative feedback of thyroxine. Consequently, the affected patients are born with goiter or develop postnatal goiter, when L-thyroxine (LT4) supplementation is delayed. Cases of thyroid cancer have been reported in congenital hypothyroidism (CH) due to dyshormonogenesis, usually of follicular histology. Clinical Case: A 22-year lady has been taking LT4 since 8-years, under the diagnosis of goitrous CH. Her mother recalled neck swelling at newborn period. However, normal newborn screening test prevented neonatal goiter from further investigation. Initial test at 8-year of age revealed normal thyroid function without thyroid auto-antibodies, diffuse enlarged thyroid gland with increased uptake on 99mTc scan, and diffuse thyroid enlargement with heterogeneous echogenicity on ultrasonography (US). The goiter size waxed and waned according to the drug compliance. The highest TSH level (normal 0.17-4.05 μIU/mL) was 8.68 μIU/mL even without medication for 8 months by her own judgement. At 11.5-years, US found isoechoic solid nodule of 1.8 x 1.7 x 1.6 cm with peripheral halo in the inferior aspect of right thyroid, which was demonstrated to be benign follicular lesion favoring nodular hyperplasia on fine needle aspiration biopsy. With good drug compliance, the nodule size decreased to 1.1 x 0.9 cm at 18-years, and peripheral calcification appeared around the isoechoic solid nodule previously reported without change in size at 22-years. NGS panel for CH reported compound heterozygous variants in TPO gene. One pathogenic variant from asymptomatic father is c.2757del;p.(Met921Trpfs*53), the other likely pathogenic variant from asymptomatic mother is c.1580G&amp;gt;T;p.(Trp527Leu). Conclusion: This case is demonstrating development of thyroid nodule even with mild increased TSH level during LT4 medication in dyshormonogenic CH caused by TPO mutation. Regular follow-up and compliance to LT4 might be important to avoid thyroid tissue stimulation and possibly nodule formation by elevated TSH. Presentation Date: Saturday, June 17, 2023