Introduction: Insulin autoimmune syndrome (IAS), or Hirata syndrome, is characterized by hyperinsulinemic hypoglycemia resulting from the presence of high titers of insulin autoantibodies (IAAs) in the absence of exogenous insulin. We present a rare case of IAS. Case: A 75-year-old female with underlying hypertension, dyslipidemia, and osteoporosis presented with symptoms suggestive of spontaneous hypoglycemia of 3 months duration. She was non-diabetic with no history of antidiabetic agents or exogenous insulin use. Notably, she had taken traditional medications 1 month prior to onset of symptoms. Her fasting blood glucose was 2 mmol/L. Serum insulin was significantly elevated at >1,000 iui/mL and serum C peptide was 2,950 pmol/L, consistent with hyperinsulinemic hypoglycemia. Blood sulfonylurea level was not available. Her complete blood count and renal and liver function were normal. Thyroid function test was normal, and a short corticotropin stimulation test showed adequate cortisol response. Computed tomography (CT) pancreas, endoscopic ultrasound and PET-CT scan with Galium-68 DOTATATE showed no evidence of insulinoma. Serum IAAs were raised at 175 IU/mL, which confirmed a diagnosis of IAS. The patient was managed with dietary modifications and advised for frequent, small meals with low glycemic index, incorporating oral raw cornstarch. She was also started on oral diazoxide 100 mg twice daily (3 mg/kg/day) due to persistent hypoglycemia. She responded well to diazoxide with no more spontaneous hypoglycemia, however, developed fluid retention which was managed with oral diuretics. Subsequently, we managed to taper and stop the diazoxide after 18 months of treatment. Patient remains well with no further episodes of hypoglycemia. Conclusion IAS may be triggered by medications or viral infections, occurs more frequently in people with autoimmune conditions, and shows genetic predisposition. However, as in our patient, IAS may be idiopathic, and the cause remains unknown. IAS is frequently self-limiting, and our patient experienced spontaneous remission with no further hypoglycemic episodes after discontinuation of treatment.
Hypoglycemia ; Insulins

Background: Catecholamines play a crucial role in muscle biogenesis, but their persistent elevation is linked to muscle wasting, which is poorly understood. This study aimed to investigate the association between catecholamine levels and age-related muscle loss. Methods: This retrospective study evaluated the plasma levels of two catecholamines, metanephrine and normetanephrine, and the clinical characteristics of 830 patients with adrenal incidentaloma on computed tomography (CT). Cross-sectional CT data at the L3 lumbar vertebrae were used to measure muscle areas. In vitro studies on C2C12 myotubes were conducted to examine β-adrenergic receptor signaling pathways and their role in myogenesis. Results: Men had significantly higher mean metanephrine levels of 0.17 nmol/L and normetanephrine levels of 0.63 nmol/L than women (P<0.05). Total abdominal muscle area was negatively correlated with catecholamine levels in both men and women, with the strongest negative correlation between normetanephrine levels and total abdominal muscle area in men (r=–0.31, P<0.001). Similarly, the strongest negative correlation between visceral fat area and metanephrine was observed in men (r=–0.25, P=0.004). Clenbuterol, a β-adrenergic receptor agonist, inhibited myogenesis, including myotube formation by extracellular signal-regulated kinase (ERK) suppression in C2C12 myoblasts. Conversely, β-blockers increased myogenesis via increasing ERK phosphorylation in C2C12 cells. These findings suggest that β-adrenergic modulation influences skeletal muscle differentiation, with ERK phosphorylation. Conclusion Catecholamine levels are associated with age, sex, muscle mass, and fat mass. Monitoring catecholamine levels, particularly in older men and in individuals with reduced muscle mass, may help manage age-related muscle loss and lead to individualized treatment strategies.

Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease around the world, and pharmacotherapy is the foremost treatment method currently. In recent decades, with the rapid development of bronchoscopic interventional therapy, endoscopic physical ablation technology presents a therapeutic effect in treating COPD, with few treatment-related side effects, showing excellent application prospects in treating COPD. Since ablation techniques in this field are emerging technologies with low patient acceptance, they are not widely used in the clinical treatment of COPD. This article reviews the development process of physical ablation techniques. Moreover, their current application status and the prospects in the field of COPD treatment are also summarized and analyzed. We hope to promote the application of physical ablation in the clinical treatment of COPD and provide practical references and a theoretical basis for the clinical treatment of COPD.

Objective: Establishment of a HPLC method for six chemical components in Saposhnikovia divaricata (prim-O-glucosylcimifugin, cimifugin, 5-O-methylvisamminoside, sec-O-glucosylhamaudol, psoralen, and imperatorin), comparison of the advantages and disadvantages of the dual-standard linear calibration method and the relative retention time method, and investigation of the feasibility of the linear calibration using two reference substances for qualitative analysis of multiple components in Saposhnikovia divaricata.
Methods: A HPLC method was employed, using 21 different brands and models of C18 columns. The mobile phase consisted of acetonitrile (A) and 0.02% phosphoric acid aqueous solution (B), with gradient elution (0-20 min, 18%A; 20-45 min, 18%A-50%A; 45-60 min, 50%A). The column temperature was set at 30 ℃, the flow rate was 1 mL·min^-1, and the detection wavelength was 254 nm.
Results: The results predicted by the linear calibration using two reference substances were accurate and superior to those of the relative retention time method, and the six components exhibited good linear relationships within their respective ranges.
Conclusion: The established linear calibration using two reference substances accurately predicts the retention times of the target components. This method is stable and reliable, providing a reference for the establishment of digital standards in traditional Chinese medicine.

This study aimed to analyze the 3D morphology of the condylar part of the occiput in a Korean population and evaluate its applicability for sex estimation. A total of 87 individuals (44 males and 43 females) were included, and measurements of the occipital condyle and foramen magnum were obtained using computed tomography–based 3D reconstructions. Intra-observer reliability was assessed, and univariate and multivariate discriminant analyses were performed to evaluate the discriminative power of each variable. Most measurements showed significant sexual dimorphism, with males generally exhibiting higher values than females. Particularly, variables related to the occipital condyle, including length, width, and area, demonstrated relatively high discriminative performance, whereas those related to the foramen magnum showed comparatively lower discriminative ability. Multivariate analysis further improved the classification accuracy, indicating that the combined use of multiple variables enhanced the ability to distinguish between sexes. These findings suggest that this approach may be particularly valuable in forensic contexts where skeletal remains are incomplete and offer a reliable alternative when more commonly used elements are unavailable.

Sleep deprivation (SD) disrupts homeostatic regulation and increases vulnerability to stress and mood disorders. This study investigated the duration-dependent effects of SD and elucidated the distinct roles of adenosine A1 receptors (A1R) and A2A receptors (A2AR) in behavioral and molecular alterations induced by 24, 48, and 72 h of SD in mice. SD for 48 h and 72 h, but not 24 h, significantly increased immobility time in the tail suspension test (TST) and forced swim test (FST), accompanied by elevated plasma corticosterone (CORT) levels, indicating a duration-dependent stress response. Hippocampal A1R mRNA expression was significantly reduced, whereas A2AR mRNA expression was markedly increased at 48 h and 72 h of SD. Pharmacological blockade of either A1R (DPCPX) or A2AR (SCH 58261) significantly attenuated SD-induced depression-like behaviors and CORT elevation, whereas activation of A1R with the agonist CPA exacerbated depression-like behavior at 24 h and 48 h of SD. These findings suggest that A2AR upregulation may represent a pathological response to prolonged SD, whereas A1R downregulation may reflect compensatory adaptation to sustained receptor activation. Taken together, our results demonstrate that A1R and A2AR play distinct roles in SD-induced depression-like behaviors.

Introduction: Subacute thyroiditis (SAT) and acute suppurative thyroiditis (AST) are two distinct inflammatory conditions but share many overlapping clinical and biochemical features, which may pose a diagnostic challenge. We report a case of SAT mimicking AST. Case: A 39-year-old female presented with a 3-week history of painful neck swelling and symptoms of thyrotoxicosis, including palpitations, heat intolerance, and diaphoresis. She had no family history of thyroid disease. On examination, she was febrile and had a smooth and tender goiter. Her blood tests showed leukocytosis with elevated erythrocyte sedimentation rate and C-reactive protein. Her thyroid function test (TFT) showed thyroid-stimulating hormone of 0.023 mIU/L and free thyroxine 4 of 32.15 pmol/L. An urgent ultrasound revealed a large, ill-defined heterogeneously hypoechoic lesion predominantly at the left lobe of the thyroid gland with mild intralesional vascularity. These were reported as features of thyroiditis with infective or early suppurative changes. Fine needle aspiration (FNA) of the lesion was attempted by the radiologist but was unsuccessful. She was treated with intravenous antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs), but symptoms persisted. Repeated ultrasound and computed tomography scans about 1 week later confirmed an enlarged thyroid gland with no obvious lesion or collection within the gland. The diagnosis was revised to SAT, and prednisolone 15 mg OD was started. This resulted in rapid improvement in her symptoms and inflammatory markers. Four weeks later, she remained asymptomatic, and prednisolone was gradually tapered off. Serial TFT monitoring showed a classic triphasic pattern with an initial hyperthyroid phase, followed by hypothyroidism before returning to euthyroidism. Conclusion SAT can present with a focal lesion on the ultrasound during the early stage of the disease, making it difficult to distinguish from a thyroid abscess due to overlapping features. Good clinical judgement guided by FNA and appropriate follow-up imaging may be helpful in differentiating between the two conditions.
Thyroiditis, Subacute ; Thyroiditis, Suppurative

Background: Graft failure (GF) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT). Secondary transplantation has been recognized as a potential curative intervention. Methods: This study aimed to investigate the characteristics and outcomes of salvage transplantation by analyzing the patients who underwent a second HCT for GF following the initial allo-HCT between 1998 and 2020. Results: Overall, 23 recipients were identified, including 14 and 9 individuals with primary and secondary GF, respectively. Nine recipients underwent a second transplant from the same donor. Familial mismatched donors predominated in the second HCT (86.9%), with reduced-intensity conditioning as the prevailing approach (60.9%). Neutrophil engraftment occurred in 17 patients (73.9%) following the second HCT at a median of 17 days (range: 9–58 days) post-transplantation. However, secondary GF subsequently occurred in 5 patients, and successful engraftment following salvage transplantation was achieved in 12 (52.2%) patients. In the entire study population, the estimated 5-year probability of overall survival (OS) and treatment-related mortality (TRM) were 30.4% and 58.5%, respectively. Among patients who achieved successful engraftment following a second transplantation, the OS and TRM rates were 41.7% and 33.3%, respectively, indicating a trend toward better OS and significantly lower TRM compared to those with GF. Notably, 17 patients died, with infection being the most common cause (n = 12), irrespective of the engraftment status. Conclusion A successful engraftment following a second allo-HCT reduced the TRM; however, the OS remained suboptimal. The effective control of infectious diseases remains crucial for patients with GF, regardless of the engraftment status following salvage transplantation.

Inflammatory response,immunosuppression,and drug sensitivity have been reported to have a significant correlation with the disulfidptosis levels in cancer patients.However,the value of disulfidpto-sis in colorectal cancer therapy remains unclear.Therefore,we classified the CRC cells into different cell types using single-cell sequencing data and cell-specific markers and analyzed their relationship with the cell disulfidptosis level.We found that the high disulfidptosis regions were concentrated in epithelial-like CRC cells.Further exploration using the disulfidptosis and programmed cell death 1 inhibitor therapy treated differential expression genes indicated that CRC patients with high disulfidptosis levels exhibited a lower risk profile and increased sensitivity to immunotherapy.By using the spatial transcriptomic analy-sis,we found that ubiquinol-cytochrome c reductase core protein 1(UQCRC1),a disulfidptosis-related gene,is highly expressed in epithelial-like CRC cells and co-localized with immune-infiltrated tumor re-gions.Additional bioinformatic analyses and experimental validation further confirmed that UQCRC1 was downregulated in CRC tissues.Overexpression of UQCRC1 suppressed CRC cell proliferation and migra-tion.These findings indicate that UQCRC1 is a potential target for CRC diagnosis and treatment.