Introduction: Non-diabetic hypoglycemia in older adults warrants careful evaluation across insulin-mediated and noninsulin-mediated causes. We present a challenging case of insulin autoimmune syndrome (IAS; Hirata’s syndrome). Case: An 85-year-old female presented with severe hypoglycemia (capillary blood glucose [CBG] 1.8 mmol/L) with reduced consciousness, preceded by 2 months of recurrent dizziness relieved by food intake. Appetite and weight were stable. Past medical history included stage 3 chronic kidney disease and osteoporosis, but no diabetes. Medication review revealed a recent 2-week course of traditional supplement, long-term Neurobion®, but no agents with recognized hypoglycemic potential. Physical examination showed a moderately built elderly female with a body mass index of 24.3 kg/m² and no Cushingoid features. Recurrent hypoglycemia (CBG nadir 1.5 mmol/L) occurred in both fasting and postprandial states, fulfilling Whipple’s triad. Baseline investigations showed an estimated glomerular filtration rate of 42 mL/min/1.73 m², AM cortisol of 700 mmol/L, and unremarkable liver and thyroid function tests. During a hypoglycemic episode (CBG 2.3 mmol/L), plasma insulin and C-peptide were inappropriately raised at 203.6 mU/L (reference interval [RI]: 3.0– 25.0) and 33 ng/mL (RI: 0.9–7.1), respectively, confirming endogenous hyperinsulinemic hypoglycemia. Polyethylene glycol precipitation showed 21% insulin recovery, raising suspicion for an autoimmune cause. Elevated insulin autoantibodies (175 AU/mL; RI <20) confirmed IAS. Computed tomography of the abdomen and endoscopic ultrasound excluded a pancreatic neuro-endocrine tumor. Nutritional management comprising frequent low glycemic index feeds and uncooked cornstarch was commenced. Diazoxide 100 mg TDS caused fluid overload and severe hyponatremia, while hypoglycemia persisted at lower doses, necessitating discontinuation. Subcutaneous octreotide 100 mg QID was required to control hypoglycemia. Prednisolone 30 mg BD improved glycemic stability. Insulin autoantibodies titer remained 175 AU/mL at 2 weeks; reassessment was conducted at 4 weeks with consideration for biologics if persistent. : doses, necessitating discontinuation. Subcutaneous octreotide 100 mg QID was required to control hypoglycemia. Prednisolone 30 mg BD improved glycemic stability. Insulin autoantibodies titer remained 175 AU/mL at 2 weeks; reassessment was conducted at 4 weeks with consideration for biologics if persistent. Conclusion Endogenous hyperinsulinemic hypoglycemia, after excluding insulinoma, should raise suspicion for IAS. Management includes removing triggers, supportive care, and immunomodulatory therapy in severe cases.

Introduction: Hurthle cell adenoma is a rare benign thyroid neoplasm that can only be diagnosed through histopathological examination. Hurthle cell neoplasm typically presents as nonfunctioning cold nodule on thyroid scintigraphy. We report a rare case of Hurthle cell adenoma presenting with thyroid storm, with unusual findings of “cold” within “hot” thyroid nodule on scintigraphy. Case: A 73-year-old male with hypertension, chronic kidney disease, coronary artery disease, and Parkinson’s disease presented to the emergency department with fever and diarrhea. His temperature was 38.4°C, heart rate 106 bpm, and blood pressure 138/75 mmHg, with atrial fibrillation and signs of heart failure. The Burch-Wartofsky score was 50, consistent with thyroid storm. Laboratory tests revealed free thyroxine 4 37.8 pmol/L (NR 11.5–22.7), free thyroxine 3 5.6 pmol/L (NR 3.5–6.5), and thyroid-stimulating hormone <0.01 mIU/L (NR 0.55– 4.78). Thyroid autoantibodies, including anti-thyroid peroxidase, anti-thyroglobulin, and thyroid-stimulating immunoglobulins, were negative (<0.10 IU/L). The thyroid storm was precipitated by invasive Klebsiella syndrome with endophthalmitis and lung and liver abscess. He was treated with Lugol’s iodine, corticosteroid, antibiotics, and carbimazole. Ultrasound thyroid revealed a mixed cystic-solid nodule in the left thyroid lobe, measuring 2.3 × 3.3 × 4.3 cm (TIRADS category 3). Technetium-99m thyroid scintigraphy demonstrated a hyperfunctioning left thyroid nodule with a focal intranodular cold spot measuring 5.0 × 3.7 cm. Fine needle aspiration cytology of the nodule was benign follicular cells. Following stabilization with anti-thyroid treatment, he underwent left hemithyroidectomy. Histopathology examination revealed a Hurthle cell adenoma without capsular or vascular invasion. Postoperatively, he remained clinically euthyroid. Surveillance ultrasound performed 8 months later showed a normal right thyroid lobe, and lifelong surveillance was planned. Conclusion This case illustrates a rare and unusual presentation of thyroid storm caused by a toxic Hurthle cell adenoma containing an intranodular cold spot on scintigraphy. To our knowledge, only one similar case has been reported in the literature, and our case is the first to present with thyroid storm.
Oxyphil Cells ; Thyroid Crisis ; Adenoma

Introduction: Long-term antithyroid drug (LT-ATD) has emerged as a feasible treatment strategy for patients who decline radioactive iodine (RAI) or thyroidectomy for relapsed or refractory Graves’ disease (GD). Benefits include faster achievement of euthyroidism, lower risk of hypothyroidism, a more favorable cardiovascular profile, and avoidance of surgical risks. Although fluctuations in thyroid status may occur despite good compliance, thyroid storm is exceedingly rare in patients on LT-ATD. While there is no specific data on the incidence of thyroid storm in this cohort, surveys suggest an overall low incidence (0.2–0.76 cases per 100,000 annually). We report a patient with stable GD who developed a thyroid storm despite more than 10 years of LT-ATD. Case: A 40-year-old female was diagnosed with GD 11 years earlier during pregnancy. Treatment was stopped at 25 weeks’ gestation, but she relapsed at 7 months postpartum and was started on carbimazole. She declined RAI or surgery following a relapse and remained on carbimazole 5–10 mg daily, with good compliance. She presented with a 1-day history of fever, cough, rhinorrhea, diarrhea, and palpitations. She was compliant with carbimazole 5 mg daily. On presentation, BP was 132/70 mmHg, HR 140 bpm, temperature 38.5°C, and SpO2 98% on air. She was alert without agitation, had a diffuse goiter, mild proptosis, and conjunctival injection, with otherwise normal findings. Electrocardiogram showed sinus tachycardia. Laboratory investigations demonstrated mild transaminitis, leukocytosis, markedly elevated free T4 (>154 pmol/L), suppressed thyroid-stimulating hormone (<0.008 mIU/L), and elevated thyroid-stimulating immunoglobulin (2.25 IU/L, reference <0.55). Thyroid function tests 1 month ago was normal. Her Burch-Wartofsky score was 60, consistent with thyroid storm, likely precipitated by upper respiratory tract infection. She improved with treatment and was discharged with carbimazole 30 mg daily with planned tapering, subsequently agreeing to RAI as definitive treatment. Conclusion Infection may trigger thyroid storm despite good compliance with LT-ATD. Patients should be counselled regarding this risk and advised to seek early medical attention if thyrotoxic symptoms recur.
Antithyroid Agents ; Thyroid Crisis

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1(SOS1-IT1)affects enhancer of zeste homolog 2(EZH2)protein expression in endometrial cancer cells Ishikawa and RL95-2.Methods Lentiviral transfection of short hairpin RNA(shRNA)and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1.The mechanism of EZH2 expression regulation was studied using Real-time PCR,Western blotting,and chromatin immunoprecipitation.Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues.Knocking down SOS1-IT1 significantly reduces the expression of EZH2,inhibited the proliferation and migration of Ishikawa and RL95-2 cells,and could reduced the acetylation of histone H3 at position 27(H3K27)and the enrichment of CREB binding protein(CBP)in the EZH2 gene promoter region.Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP.CBP could bind to SOS1-IT1 RNA,and this binding ability was weakened when CBP was knocked down.Conclusion SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region,thereby affecting the proliferation and migration ability of endometrial cancer cells.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

AIM To investigate the protective effects and the mechanism of the Liuwei Dihuang Pills on mouse brain microvascular endothelial(bEnd.3)cells damaged by β-Amyloid protein1-40(Aβ1-40).METHODS CCK8 method was used to detect the effects of Aβ1-40 and medicated serum of Liuwei Dihuang Pills(MSLDP)on cell activity,and to screen the appropriate concentration.bEnd.3 cells of the control group,the Aβ1-40 group,the MSLDP+Aβ1-40 group and the MSLDP group had their low density lipoprotein-associated protein 1(LRP1),receptor for advanced glycation end products(RAGE),matrix metalloproteinase-2(MMP-2),MMP-9,scaffold protein zonule protein-1(ZO-1)detected by Western blot.bEnd.3 cells assigned into the control group,the Aβ1-40 group,the FPS-ZM1(RAGE inhibitor)+Aβ1-40 group and the FPS-ZM1+Aβ1-40+MSLDP group had their expressions of RAGE,MMP-9,MMP-2 and ZO-1 detected by Western blot as well.RESULTS The cell activity of bEnd.3,was dose-dependently decreased by Aβ1-40(P<0.01),but was protected by MSLDP(P<0.05,P<0.01).And 10 μmol/L Aβ1-40 and 10%MSLDP were selected for subsequent experiments.Compared with the control group,the Aβ1-40 group displayed increased protein expressions of RAGE,MMP-2 and MMP-9(P<0.01),decreased protein expressions of LRP1,ZO-1 and BDNF(P<0.05,P<0.01),and decreased fluorescence intensities of LRP1 and ZO-1(P<0.01).Compared with the Aβ1-40 group,the MSLDP group shared decreased expressions of RAGE,MMP-2,MMP-9 proteins and RAGE fluorescence intensity(P<0.05,P<0.01),and increased expressions of LRP1,ZO-1 and BDNF proteins,and the fluorescence intensity of LRP1 and ZO-1(P<0.05,P<0.01);the Aβ1-40+FPS-ZM1 group displayed decreased protein expressions of MMP-2,MMP9 and RAGE(P<0.05,P<0.01),and increased ZO-1 protein expression(P<0.05);and the Aβ1-40+FPS-ZM1+ MSLDP group displayed an even more decreased protein expressions of MMP-2,MMP9 and RAGE(P<0.01),increased ZO-1 protein expression(P<0.01)due to the the combination use of FPS-ZM1 and MSLDP.CONCLUSION Liuwei Dihuang Pills can protect the tight junction of bEnd.3 injured by Aβ1-40 and neurovascular units from Alzheimer's disease by alleviating the dysfunction of the blood-brain barrier via RAGE-mediated MMP-2/MMP-9 pathway inhibition.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.