ABSTRACT Background Tauroursodeoxycholic acid (TUDCA) has been shown to improve endothelial dysfunction in type 2 diabetes mellitus (T2DM). However, its role in attenuating endothelial insulin resistance in diabetes is not well understood. Objectives This study aimed to investigate TUDCA’s potential therapeutic effect on endothelial insulin resistance and its underlying mechanisms. Methods Twenty-seven male Sprague Dawley rats were categorized into control (CON, n = 9), diabetes (DM, n = 9), and diabetes treated with TUDCA (DMT, n = 9). Diabetes was induced using a high-fat diet and low-dose streptozotocin. TUDCA (150 mg/kg) was administered to the DMT group during the last two weeks of a 15-week study. Aortic tissues were analyzed for insulin-mediated relaxation, endoplasmic reticulum (ER) stress markers [inositol-requiring kinase 1 (IRE-1), protein kinase-like ER kinase (PERK), and binding immunoglobulin protein (BIP)], end othelial function markers [endothelial nitric oxide synthase (eNOS), protein kinase B (Akt), and insulinreceptor substrate-1 (IRS-1)], oxidative stress [superoxide dismutase activity (SOD) and malondialdehyde level (MDA)] and inflammation [tumor necrosis factor-alpha (TNF-a)] markers. Results Insulin-mediated relaxation was impaired in diabetic rats (−56.7%) compared to controls (0%), accompanied by elevated ER stress markers and reduced eNOS, Akt, and IRS-1 expression. TUDCA treatment improved relaxation responses (−6.2%) significantly reduced ER stress markers and restored the expression of endothelial markers.

ABSTRACT Objective Orexin-A (OXA) is a hypothalamic neuropeptide implicated in glucose regulation and insulin sensitivity. Given the central role of insulin resistance in polycystic ovary syndrome (PCOS), this study evaluated serum OXA levels in women with PCOS. Methods This cross-sectional case-control study included 88 women with PCOS and 88 age- and body mass index-matched controls. Serum OXA levels were quantified using a commercial ELISA kit. Results Serum OXA levels were significantly lower in women with PCOS than in controls (321.53 ng/L vs. 385.06 ng/L, p = 0.012). A significant negative correlation was observed between the modified Ferriman-Gallwey score and serum OXA level. In the ROC analysis, a serum OXA level of 369.55 ng/L yielded a sensitivity of 55.7% and a specificity of 55.7% (AUC: 0.610) for detecting PCOS. Conclusions Serum OXA concentrations were reduced in women with PCOS. Whether this reduction contributes to PCOS pathogenesis or reflects a secondary alteration remains uncertain.

ABSTRACT Introduction Continuous glucose monitoring (CGM) demonstrates significant benefits in glycemic control for both type 1 and type 2 diabetes, including reductions in HbA1c, increased time-in-range, and decreased hypoglycemia. Methods In this article, we review the recent American Diabetes Association guidelines recommending real-time CGM for adults with type 2 diabetes, including those not using insulin. Results While acknowledging the documented advantages, CGM remains underutilized, with many barriers, particularly in primary care settings and among racially diverse or lower socioeconomic populations. Discussion This review outlines positive strategies to address barriers to CGM-adoption, optimize glycemic control and thereby potentially reduce cardiovascular-kidney-metabolic complications.

ABSTRACT Objective: This study aims to investigate the clinical and ultrasonographic features of thyroid swelling following fine-needle aspiration biopsy (FNAB), and to distinguish between symptomatic and asymptomatic forms. Methods: We retrospectively reviewed 872 patients who underwent thyroid ultrasonography before and after FNAB between January and November 2024. Patients showing new hypoechoic cracking after FNAB were identified. Clinical symptoms, degree of thyroid swelling, and outcomes were evaluated. Results: Hypoechoic cracking developed in 18 patients (2.1%), appearing immediately in 17 and at 4 hours in one. Three patients (17%) experienced symptoms such as pain or compression, all with thyroid swelling exceeding 1.8-fold the original size. The remaining 15 patients were asymptomatic, with swelling less than 1.5-fold. No clinical characteristics were significantly associated with the development of symptoms. All patients recovered spontaneously; two symptomatic cases received steroid treatment. Conclusion: Post-FNAB thyroid swelling can be classified into two entities: typical, symptomatic acute transient thyroid swelling (ATTS) and a newly proposed asymptomatic form, acute transient thyroid cracking (ATTC). Recognizing ATTC as a mild, self-limiting condition is important for avoiding unnecessary treatment and alleviating patient concern.

ABSTRACT Introduction There are few studies investigating oxidative stress in hyperprolactinemia. We aimed to analyze the associations between hyperprolactinemia, its treatment, and oxidative stress parameters. Methods Twenty patients who had hyperprolactinemia secondary to a prolactin-secreting pituitary tumor, and 20 age- and BMI-matched healthy controls were prospectively included. Patients were studied at recruitment and six months post-treatment. Markers indicating protein oxidation and antioxidant system were analyzed. Results Serum prolactin level in the patient group (13 female, 7 male) was significantly higher than controls. Myeloperoxidase (MPO) activity and advanced oxidation protein product (AOPP) levels were comparable between the groups, while pyrrolized protein, and protein carbonyl compound (PCC) levels were significantly higher, and thiol levels lower in the patients at baseline. A decrease in prolactin levels along with improvements in estradiol (in females) and testosterone (in males) levels were observed following treatment. After treatment of hyperprolactinemia a significant decrease in AOPP, PCC, pyrrolized protein, and an increase in thiol levels were observed. MPO activity remained stable. Discussion In addition to reproductive dysfunctions and altered sex hormones, hyperprolactinemia is associated with oxidative stress, which improves four to six months after cabergoline treatment.

ABSTRACT Background While numerous studies have explored treatment outcomes for the overall ACC patient cohort, data on the subpopulation of patients with recurrent disease are limited. Therefore, the aim of this study was to assess treatment outcomes in patients with recurrent ACC. Methods In this retrospective study, we included 18 patients median age 49 years (42–62); 67% female) diagnosed with recurrent ENSAT stage I-III ACC who underwent either R0 (n = 16) or Rx (n = 2) surgical resection of the tumor. Results The median time from the initial surgery to ACC recurrence was 29 months (IQR 18–50). Seven patients (39%) manifested local recurrence, while 11 patients (61%) developed distant metastases. The median follow-up duration after tumor recurrence was 32 months (IQR 25–53). Regarding the treatment of ACC recurrence, 10 patients underwent a second surgery either as an alone procedure (n = 4), or in combination with mitotane (n = 4), mitotane and chemotherapy (n = 1), or mitotane combined with radiotherapy (n = 1). The remaining patients received treatment involving chemotherapy±mitotane (n = 4) and locoregional therapy ±chemotherapy (n = 3). One patient chose not to proceed with further management and follow-up. The median PFS was 17 (95% CI 8–26) months while the median OS was not reached. In the multivariate model, increased mortality was associated with advanced age (p = 0.04) and a shorter interval to ACC recurrence (p = 0.03). Conclusion A significant proportion of patients with ACC recurrence experience disease progression or second recurrence, despite all treatment efforts. Nevertheless, by integrating diverse treatment modalities, many patients have the potential to attain long-term survival.

ABSTRACT Background Monogenic diabetes often occurs as a result of single-gene mutations. The illness is minimally affected by environmental and behavioral factors, and it constitutes around one to five percent of all cases of diabetes. Methods Newborn diabetes mellitus (NDM) and maturity-onset diabetes of the young (MODY) are the predominant causes of monogenic diabetes, accounting for a larger proportion of cases, while syndromic diabetes represents a smaller percentage. MODY, a group of inherited non-autoimmune diabetes mellitus disorders, is quite common. However, it remains frequently misdiagnosed despite increasing public awareness. The condition is characterized by insulin resistance, the development of diabetes at a young age (before 25 years), mild high blood sugar levels, inheritance in an autosomal dominant pattern, and the preservation of natural insulin production. Results Currently, there are 14 distinct subtypes of MODY that have been identified. Each subtype possesses distinct characteristics in terms of their frequency, clinical symptoms, severity of diabetes, related complications, and response to medicinal interventions. Due to the clinical similarities, lack of awareness, and high expense of genetic testing, distinguishing between type I (T1D) and type II diabetes mellitus (T2D) can be challenging, resulting in misdiagnosis of this type of diabetes. As a consequence, a significant number of individuals are being deprived of adequate medical attention. Accurate diagnosis enables the utilization of novel therapeutic strategies and enhances the management of therapy in comparison to type II and type I diabetes. Conclusion This article offers a concise overview of the clinical subtypes and characteristics of monogenic diabetes. Furthermore, this article discusses the various subtypes of MODY, as well as the process of diagnosing, managing, and treating the condition. It also addresses the difficulties encountered in detecting and treating MODY.

ABSTRACT Objective Subacute thyroiditis(SAT) is an acute inflammatory, self-limited, and destructive disease of the thyroid gland. Although it is a temporary disease, it has permanent consequences. We aim to investigate the influences of the treatment choice on permanent hypothyroidism occurring after SAT and whether there are predictive factors for the development of permanent hypothyroidism. Methods We retrospectively investigated 57 SAT patients admitted to our tertiary hospital between 2017 and 2019. After excluding 6 patients, demographic, clinical, laboratory, and imaging findings of 36 patients treated with NSAIDs and 15 patients treated with corticosteroids were compared. The median duration of follow-up was 4 (3.5-5.5) years. Results Permanent hypothyroidism occurred in 16 patients (31.4%) of 51 patients. It developed at a significantly higher rate in NSAID users (p=0.019). There was no significant difference in the occurrence of transient hypothyroidism and recurrence (p=0.472, p=0.082). The early maximum TSH values were strongly associated with permanent hypothyroidism. The Odds Ratio (OR) value was 2.59 (95% CI = 1.26 – 5.33, p=0.009), Nagelkerke R2 = 0.821. The early maximum TSH level had a predictive value, with an AUC of 0.966 for post-SAT permanent hypothyroidism (p<0.001). The cutoff values for the early maximum TSH were 9.07uIU/ml (81.3% sensitivity, 100% specificity), and 7.05 uIU/ml (87.5% sensitivity, 94.3% specificity). Conclusion Corticosteroid therapy is significantly effective in preventing permanent hypothyroidism from developing after SAT. The early maximum TSH values are an indicator for the prediction of the development of permanent hypothyroidism.

ABSTRACT Purpose: Osteoporosis is characterized by low bone mineral density (BMD) and high risk of osteoporotic fracture (OF). Peripheral blood monocytes (PBM) can differentiate into osteoclasts to resorb bone. This study was to identify PBM-expressed proteins significant for osteoporosis in Chinese Han elderly population (>65 years), and focused on two phenotypes of osteoporosis: low BMD and OF. Methods: Label-free quantitative proteomics was employed to profile PBM proteome and to identify differentially expressed proteins (DEPs) between OF (N=27) vs. non-fractured (NF, N=24) subjects and between low BMD (N=12) vs. high BMD (N=12) subjects in women. Western blotting (WB) was conducted to validate differential expression, and ELISA to evaluate translational value for secretory protein of interest. Results: We discovered 59 DEPs with fold change (FC)>1.3 (P<1×10-5), and validated the significant up-regulation of pyruvate kinase isozyme 2 (PKM2) with osteoporosis (P<0.001). PKM2 protein upregulation with OF was replicated with PBM in men (P=0.04). Plasma PKM2 protein level was significantly elevated with OF in an independent sample (N=100, FC=1.68, P=0.01). Pursuant functional assays showed that extracellular PKM2 protein supplement not only promoted monocyte trans-endothelial migration, growth, and osteoclast differentiation (marker gene expression), but also inhibited osteoblast growth, differentiation (ALP gene expression), and activity. Conclusion: The above findings suggest that PKM2 protein is a novel osteoporosis-associated functional protein in Chinese Han elderly population. It may serve as a risk biomarker and drug target for osteoporosis.

ABSTRACT Background The purpose of this study was to investigate the preoperative prediction of large-number central lymph node metastasis (CLNM) in single thyroid papillary carcinoma (PTC) with negative clinical lymph nodes. Methods A total of 634 patients with clinically lymph node-negative single PTC who underwent thyroidectomy and central lymph node dissection at the First Affiliated Hospital of Anhui Medical University and the Nanchong Central Hospital between September 2018 and September 2021 were analyzed retrospectively. According to the CLNM status, the patients were divided into two groups: small-number (≤5 metastatic lymph nodes) and large-number (>5 metastatic lymph nodes). Univariate and multivariate analyses were used to determine the independent predictors of large-number CLNM. Simultaneously, a nomogram based on risk factors was established to predict large-number CLNM. Results The incidence of large-number CLNM was 7.7%. Univariate and multivariate analyses showed that age, tumor size, and calcification were independent risk factors for predicting large-number CLNM. The combination of the three independent predictors achieved an AUC of 0.806. Based on the identified risk factors that can predict large-number CLNM, a nomogram was developed. The analysis of the calibration map showed that the nomogram had good performance and clinical application. Conclusion In patients with single PTC with negative clinical lymph nodes large-number CLNM is related to age, size, and calcification in patients with a single PTC with negative clinical lymph nodes. Surgeons and radiologists should pay more attention to patients with these risk factors. A nomogram can help guide the surgical decision for PTC.