ObjectiveTo investigate the therapeutic mechanism of Xuefu Zhuyutang （XFZYT） for metabolic-associated fatty liver disease （MAFLD） through integrated network pharmacology and animal experiments. MethodsNetwork pharmacology was utilized to predict the core components， key therapeutic targets， and signaling pathways of XFZYT in the treatment of MAFLD. For animal experiments， a rat model of MAFLD was established by feeding a high-cholesterol diet for 4 weeks. Intervention was then administered with low-dose （2 g·kg^-1） and high-dose （4 g·kg^-1） XFZYT for 2 weeks. Biochemical assays were performed to measure the serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. In addition， the activities of superoxide dismutase （SOD） and catalase （CAT） and levels of malondialdehyde （MDA） and glutathione （GSH） in the serum were measured. The same way was adopted to measure the levels of TC and TG in the liver tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify the serum levels of interleukin （IL）-6， IL-1β， and tumor necrosis factor-alpha （TNF-α）. Histopathological evaluations included hematoxylin and eosin （HE） staining for liver tissue morphology， Oil Red O staining for lipid deposition， and dihydroethidium （DHE） probe staining for reactive oxygen species （ROS） levels. Western blot analysis was conducted to assess the protein levels of AMP-activated protein kinase （AMPK）， phosphorylated （p）-AMPK， nuclear factor erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， nuclear factor-kappa B （NF-κB）， and p-NF-κB in the liver tissue. Untargeted metabolomics analysis of the serum was performed by liquid chromatography-tandem mass spectrometry （LC-MS/MS）. ResultsNetwork pharmacology analysis predicted 155 potential targets of XFZYT for MAFLD treatment， with core targets including signal transducer and activator of transcription 3 （STAT3）， protein kinase B1 （Akt1）， TNF， and IL-6. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment primarily implicated the AMPK signaling pathway. Animal experiments demonstrated that compared with the normal group， the model group exhibited dyslipidemia， hepatic function impairment， pronounced hepatic lipid deposition， and inflammatory manifestations， with elevated serum levels of AST， ALT， TC， TG， LDL， and MDA （P<0.05）， reduced HDL and GSH levels plus decreased SOD and CAT activities （P<0.05）， downregulated protein levels of Nrf2， HO-1， and p-AMPK （P<0.05）， and upregulated protein level of p-NF-κB （P<0.05） in the liver tissue. Compared with the model group， XFZYT intervention groups showed significant amelioration of dyslipidemia and hepatic function impairment， markedly reduced hepatic lipid deposition and inflammatory cell infiltration， decreased serum levels of AST， ALT， TC， TG， LDL， and MDA （P<0.05）， increased HDL and GSH levels plus enhanced SOD and CAT activities （P<0.05）， upregulated protein levels of Nrf2， HO-1， and p-AMPK （P<0.05）， and downregulated protein level of p-NF-κB （P<0.05）. Serum metabolomics revealed 511 differentially expressed metabolites （231 upregulated and 280 downregulated） between normal and model groups， while XFZYT groups versus model group showed 94 differential metabolites （51 upregulated and 43 downregulated）. Among them， 11 metabolites displayed the most significant alterations， with enriched pathways including glycerolipid metabolism， cholesterol metabolism， and insulin resistance， multiple of which demonstrated AMPK association. ConclusionXFZYT alleviates MAFLD by regulating the AMPK signaling pathway and associated metabolic networks.

ObjectiveTo develop a full-process data platform of renal rehabilitation, diagnosis and quality control information. MethodsA hierarchical architectural design was proposed, adhering to clinical pathway models and standardized data protocols. The platform comprehensively covered assessment, intervention, follow-up and quality control for maintenance hemodialysis (MHD) patients. By integrating multidisciplinary resources and standardizing rehabilitation workflows, it delivered standardized and intelligent rehabilitation services. ResultsThe platform achieved standardized and intelligent management of rehabilitation services, effectively improved the physiological function, psychological state and quality of life convenience for MHD patients, while significantly reduced the economic and care burden on patients' families and society. ConclusionThe rehabilitation service model based on a full-process data platform may provide scientific and systematic support for MHD patients.

ObjectiveTo investigate the association of liver fibrosis scores and inflammation markers with gallstones in patients with metabolic dysfunction-associated fatty liver disease （MAFLD）， as well as the mediating role of liver fibrosis scores in the relationship between inflammation markers and gallstones. MethodsA total of 14 567 patients who received physical examination and were diagnosed with MAFLD in Subei People’s Hospital from January 2014 to June 2023 were enrolled in this study， and according to the results of abdominal color Doppler ultrasound， they were divided into gallstone group with 1 724 patients and non-gallstone group with 12 843 patients. Related clinical data were collected from all patients， including demographic data， medical history， family history， physical examination， Color Doppler ultrasound， and biochemical parameters. The biomarkers associated with metabolic disorders and insulin resistance included triglyceride-glucose index （TyG）， TyG-body mass index （BMI） index， atherogenic index of plasma （AIP）， and non-high-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol ratio （NHHR）； the biomarkers associated with inflammation and nutritional status included neutrophil-to-lymphocyte ratio （NLR）， neutrophil percentage-to-albumin ratio （NPAR）， and monocyte-to-lymphocyte ratio （MLR）； the biomarkers for assessing liver fibrosis degree and liver function included albumin-bilirubin （ALBI） score， NAFLD fibrosis score （NFS）， fibrosis-4 （FIB-4） index， and aspartate aminotransferase-to-platelet ratio index （APRI）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Multivariate Logistic regression analysis， restricted cubic spline analysis， and mediating effect analysis were used to assess the association of liver fibrosis markers and inflammation markers with the risk of gallstones. ResultsThe prevalence rate of gallstones was 11.8% among the MAFLD patients. There were significant differences between the gallstone group and the non-gallstone group in sex， age， smoking history， diabetes， hypertension， lymphocytes， platelets， glucose， albumin， serum uric acid， alanine aminotransferase， aspartate aminotransferase， red blood cell， NLR， NPAR， MLR， NFS， FIB-4 index， and ALBI score （all P<0.05）. The multivariate Logistic regression analysis showed that NLR （odds ratio ［OR］=1.091， 95% confidence interval ［CI］： 1.028　—　1.160， P<0.05）， NPAR （OR=1.073， 95%CI： 1.042　—　1.105， P<0.05）， MLR （OR=1.142， 95%CI： 1.057　—　1.232， P<0.05）， NFS （OR=1.239， 95%CI： 1.190　—　1.291， P<0.05）， and FIB-4 index （OR=1.326， 95%CI： 1.241　—　1.417， P<0.05） were influencing factors for the prevalence rate of gallstones. The restricted cubic spline analysis showed a significant non-linear association between NFS/FIB-4 index and the risk of gallstone （non-linear P<0.05）. The mediating effect analysis further showed that the association of NLR， MLR， and NPAR with gallstones was partially mediated by NFS or FIB-4 index， with a mediating effect accounting for 36.79%、28.09%、29.67% and 18.31%、17.70、11.57%， respectively. ConclusionNFS and FIB-4 index have a non-linear association with the prevalence rate of gallstones in MAFLD patients， and they also mediate the association of NLR， NPAR， and MLR with the risk of gallstone.

ObjectiveTo investigate the present situation of input, output, outcome and impact of all registered community-based rehabilitation stations in Inner Mongolia in China, and analyze how the input predict the output, outcome and impact. MethodsFrom March 1st to April 30th, 2025, a questionnaire survey was conducted on all registered community-based rehabilitation stations in Inner Mongolia, covering four dimensions: input, output, outcome and impact. A total of 1 365 questionnaires were distributed. The input included four items: laws and policies, human resources, equipment and facilities, and rehabilitation information management. The output included two items: technical paths and benefits/effectiveness. The outcome included three items: coverage rates, rehabilitation interventions and functional results. The impact included two items: health and sustainability. Each item contained several questions, all of which were described in a positive way. Each question was scored from one to five. A lower score indicated that the situation of the community-based rehabilitation station was more in line with the content described in the question. Regression analysis was performed using the total score of each item of input dimension as independent variables, and the total scores of the output, outcome and impact dimensions as dependent variables. ResultsA total of 1 262 valid questionnaires were collected. The mean values of input, output, outcome and impact of community-based rehabilitation stations were 1.827 to 1.904, with coefficient of variation of 45.892% to 49.239%. The regression analysis showed that, rehabilitation information management, human resources, and laws and policies significantly predicted the output dimension (R² = 0.910, P < 0.001). Meanwhile, all four items in the input dimension predicted both the outcome (R² = 0.850, P < 0.001) and impact dimensions (R² = 0.833, P < 0.001). ConclusionInput, output, outcome and impact of the community-based rehabilitation stations in Inner Mongolia were generally in line with the content of the questions, although some imbalances were observed. Additionally, the input of community-based rehabilitation stations could significantly predict their output, outcome and impact.

ObjectiveTo investigate the association between noninvasive liver fibrosis markers and carotid plaque （CP） in patients with lean metabolic dysfunction-associated fatty liver disease （MAFLD）， and to provide a basis for screening high-risk populations. MethodsA total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort， with the presence or absence of CP as the outcome， and fibrosis-4 （FIB-4） index and nonalcoholic fatty liver disease fibrosis score （NFS） were used to assess liver fibrosis degree. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis， the restricted cubic spline analysis， the receiver operating characteristic curve， and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. ResultsThe prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group（n=607）， the CP group （n=350） had a significantly higher proportion of male patients， a significantly higher proportion of patients with smoking/diabetes/hypertension， and significantly higher levels of age， creatinine， blood urea nitrogen， triglycerides， fasting blood glucose， aspartate aminotransferase， aspartate aminotransferase/alanine aminotransferase ratio， NFS， and FIB-4 index， as well as significantly lower levels of platelet count and albumin （all P<0.05）. The multivariate logistic regression analysis showed that after adjustment for confounding factors， FIB-4 index （odds ratio［OR］=2.979， 95% confidence interval［CI］：2.141 — 4.219， P<0.001） and NFS （OR=1.747， 95%CI： 1.499 — 2.046， P<0.001） were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers， and its mediating effect accounted for 39.5% — 40.8% of the total effect （P<0.001）. ConclusionIn patients with lean MAFLD， NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP， and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.

BACKGROUND:Epidemiological studies indicate that individuals with neurodegenerative diseases exhibit a comparatively lower risk of developing the majority of cancers.Although the precise mechanisms underlying this inverse correlation remain unclear,it is noteworthy that aberrant glucose metabolism,a pathological factor common to both conditions,may significantly contribute to this association.OBJECTIVE:To review the potential relationship between cancers and neurodegenerative diseases in glucose metabolism.METHODS:PubMed was searched for relevant literature using the search terms of"cancer,neurodegenerative diseases,Alzheimer's disease,Parkinson's disease,metabolic reprogramming,glucose metabolism,aerobic glycolysis,neuroprotection,aging,"and 136 articles were finally included for analysis.RESULTS AND CONCLUSION:Cancer and neurodegenerative diseases exhibit a profound pathological correlation at the level of glucose metabolism imbalance associated with aging.Cancer cells promote uncontrolled proliferation,invasion,and metastasis through the persistent activation of aerobic glycolysis,whereas neurodegenerative diseases are characterized by a reduction in aerobic glycolysis.Restoring aerobic glycolysis may confer neuroprotective effects and delay disease progression.The key nodes of glucose metabolism demonstrate a bidirectional regulatory pattern:metabolic regulators,which are significantly upregulated or aberrantly activated in cancer,are inhibited or functionally inactivated in neurodegenerative diseases.Mitochondria play a crucial role in mediating the aging process through the regulation of reactive oxygen species homeostasis and mitochondrial autophagy.They establish regulatory networks that connect cancer and neurodegenerative diseases,and maintaining their functional homeostasis is of paramount importance for disease prevention and treatment.

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.

ObjectiveTo develop and preliminarily validate a prediction model for brace treatment failure risk in patients with adolescent idiopathic scoliosis (AIS), based on information obtained before brace treatment and during initial brace fitting. MethodsA total of 191 patients with AIS who initiated thoracolumbosacral orthosis treatment at Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from March, 2015 to August, 2024 and had determinable outcomes were retrospectively included. Patients were divided according to a prespecified scheme into a training set (n = 133) and a validation set (n = 58). Brace treatment failure was defined as progression of the major-curve Cobb angle by ≥ 5° from baseline during follow-up or at brace weaning, or a final major-curve Cobb angle > 45°. Logistic regression, random forest, support vector machine with radial basis function kernel, and extreme gradient boosting (XGBoost) models were developed using routinely available clinical and radiographic variables before brace treatment and during initial brace fitting. Stratified five-fold cross-validation was used for hyperparameter tuning in the training set. Model performance was evaluated in the validation set using the area under the receiver operating characteristic curve (AUC), area under the precision-recall curve (AUPRC), Brier score, calibration curves, and decision curve analysis (DCA). SHapley Additive exPlanations (SHAP) was used to interpret the main explanatory model. ResultsIn cross-validation of the training set, both random forest and XGBoost showed good discriminative performance, with cross-validation-AUC values of 0.871 and 0.880, respectively. In the validation set, the AUC values of random forest and XGBoost were 0.888 and 0.899, the AUPRC values were 0.678 and 0.830, and the Brier scores were 0.086 and 0.076, respectively. Random forest was selected as the primary model for interpretation, with a calibration intercept of 0.091 and a calibration slope of 0.995. SHAP analysis indicated that the in-brace correction rate and the major-curve Cobb angle measured in the brace contributed most to the model predictions. ConclusionThe random forest model developed using routinely available pretreatment and initial-fitting variables shows preliminary predictive value for brace treatment failure risk in AIS, and may provide quantitative support for follow-up scheduling, brace-fit reassessment and early adherence-oriented management.

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