1.Serpina3c Mitigates Adipose Tissue Inflammation by Inhibiting the HIF1α-Mediated Endoplasmic Reticulum Overoxidation in Adipocytes
Yu JIANG ; Jia-Qi GUO ; Ya WU ; Peng ZHENG ; Shao-Fan WANG ; Meng-Chen YANG ; Gen-Shan MA ; Yu-Yu YAO
Diabetes & Metabolism Journal 2026;50(1):62-76
Background:
Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity.
Methods:
Wild type and Serpina3c knockout (Serpina3c–/–) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c–/– mice to induce eWAT-adipocyte- specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes.
Results:
Serpina3c–/– mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation.
Conclusion
These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.
2.The role of bile acid dynamics in inflammatory bowel disease and metabolic dysfunction-associated steatotic liver disease
Si-Rui Yu ; Run Sun ; Mei-Ya Shi ; Mei Yang ; Kun Chen ; Qiong Pan ; Ling Zhao ; Ming-Yue Wu ; Jin Chai
Liver Research 2026;10(1):35-50
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is higher among individuals with inflammatory bowel disease (IBD) than in the general population. Emerging evidence indicates that the development of MASLD in patients with IBD may occur independently of traditional metabolic risk factors, suggesting a unique pathophysiological mechanism distinct from conventional MASLD pathways. Bile acids (BAs), which act as critical signaling molecules in enterohepatic circulation, play an essential role in maintaining gastrointestinal homeostasis through bidirectional gut–liver axis communication. These molecules are increasingly recognized as pivotal regulators in the progression of both MASLD and IBD. While previous studies have characterized the dynamics of BA in blood or fecal samples under both conditions, a comprehensive understanding of their metabolic profiles and the associated interactions within the gut–liver axis is still lacking. This review synthesizes current evidence from studies employing BA metabolomics to investigate IBD and MASLD. By focusing on BA signatures, we summarize conserved alterations between these two conditions and their potential mechanisms of disease progression. Our review advances understanding of BA-mediated pathways in IBD and MASLD, providing a foundation for assessing their roles in contributing to the pathogenesis of MASLD in patients with IBD.
3.Research progress on the structural modification of isosteviol and the biological activities of its derivatives
Li-jun ZHAO ; You-fu YANG ; Tong-sheng WANG ; Yan-li ZHANG ; Ya WU
Acta Pharmaceutica Sinica 2025;60(1):22-36
Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.
4.Frontal and Parietal Alpha Asymmetry as Biomarkers for Negative Symptoms in Schizophrenia
Yao-Cheng WU ; Chih-Chung HUANG ; Yi-Guang WANG ; Chu-Ya YANG ; Wei-Chou CHANG ; Chuan-Chia CHANG ; Hsin-An CHANG
Psychiatry Investigation 2025;22(4):435-441
Objective:
Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA).
Methods:
The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox.
Results:
Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%.
Conclusion
This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.
5.Frontal and Parietal Alpha Asymmetry as Biomarkers for Negative Symptoms in Schizophrenia
Yao-Cheng WU ; Chih-Chung HUANG ; Yi-Guang WANG ; Chu-Ya YANG ; Wei-Chou CHANG ; Chuan-Chia CHANG ; Hsin-An CHANG
Psychiatry Investigation 2025;22(4):435-441
Objective:
Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA).
Methods:
The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox.
Results:
Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%.
Conclusion
This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.
6.Frontal and Parietal Alpha Asymmetry as Biomarkers for Negative Symptoms in Schizophrenia
Yao-Cheng WU ; Chih-Chung HUANG ; Yi-Guang WANG ; Chu-Ya YANG ; Wei-Chou CHANG ; Chuan-Chia CHANG ; Hsin-An CHANG
Psychiatry Investigation 2025;22(4):435-441
Objective:
Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA).
Methods:
The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox.
Results:
Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%.
Conclusion
This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.
7.Severity Assessment Parameters and Diagnostic Technologies of Obstructive Sleep Apnea
Zhuo-Zhi FU ; Ya-Cen WU ; Mei-Xi LI ; Ping-Ping YIN ; Hai-Jun LIN ; Fu ZHANG ; Yu-Xiang YANG
Progress in Biochemistry and Biophysics 2025;52(1):147-161
Obstructive sleep apnea (OSA) is an increasingly widespread sleep-breathing disordered disease, and is an independent risk factor for many high-risk chronic diseases such as hypertension, coronary heart disease, stroke, arrhythmias and diabetes, which is potentially fatal. The key to the prevention and treatment of OSA is early diagnosis and treatment, so the assessment and diagnostic technologies of OSA have become a research hotspot. This paper reviews the research progresses of severity assessment parameters and diagnostic technologies of OSA, and discusses their future development trends. In terms of severity assessment parameters of OSA, apnea hypopnea index (AHI), as the gold standard, together with the percentage of duration of apnea hypopnea (AH%), lowest oxygen saturation (LSpO2), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO2 plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.
8.Comparison of clinical characteristics between primary bilateral macronodular adrenal hyperplasia and adrenal cortisol-producing adenoma
Bing LI ; Ming-Xiu YANG ; Huai-Jin XU ; Jing-Xuan WANG ; Qing-Zheng WU ; Ya-Jing WANG ; Yi-Jun LI ; Kang CHEN ; Yu CHENG ; Qi NI ; Ya-Qi YIN ; Li ZANG ; Qing-Hua GUO ; Jian-Ming BA ; Wei-Jun GU ; Jing-Tao DOU ; Zhao-Hui LYU ; Yi-Ming MU
Medical Journal of Chinese People's Liberation Army 2025;50(7):779-785
Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.
9.Clinical and pathological characteristics of adrenal cortical carcinoma:a single-center retrospective study
Qing-Zheng WU ; Ming-Xiu YANG ; Bing LI ; Shu-Ying LI ; Zi-Xin GUO ; Yi-Jun LI ; Ya-Qi YIN ; Ya-Jing WANG ; Kang CHEN ; Li ZANG ; Wei-Jun GU ; Yi-Ming MU ; Zhao-Hui LYU
Medical Journal of Chinese People's Liberation Army 2025;50(7):786-792
Objective To investigate the clinical and pathological characteristics of adrenal cortical carcinoma(ACC),compare differences between hypercortisolism and non-functional ACC,and assess the diagnostic value of indicators such as Ki-67 index.Methods The clinical data of 57 ACC patients admitted to the First Medical Center of Chinese PLA General Hospital from January 2015 to March 2025 were retrospectively analyzed.According to the results of endocrine function assessment,47 of these patients were divided into hypercortisolism group(n=19)and non-functional group(n=28).The differences in clinical and pathological characteristics between the two groups were compared,and non-parametric tests and Spearman correlation analysis were used to explore the relationship between Ki-67 index and tumor stage as well as imaging features.Results Among the 57 patients,there were 20 males and 37 females,with a male-to-female ratio of 1:1.85.The age ranged from 16 to 76 years,and the age at diagnosis was(48.7±13.3)years.The tumor diameter was(10.53±4.14)cm.The tumors were located on the right side in 12 cases(21.1%),on the left side in 34 cases(59.6%),and bilaterally in 11 cases(19.3%).Among them,16 cases(28.1%)were complicated with glucose metabolism disorders,31 cases(54.3%)had hypertension,and 20 cases(35.1%)had hypokalemia.According to ENSAT staging,there were 0 cases in stage Ⅰ,15 cases(26.3%)in stage Ⅱ,24 cases(42.1%)in stage Ⅲ,and 18 cases(31.6%)in stage Ⅳ.Endocrine function assessment was completed in 47 of the 57 patients,including 28 cases(59.6%)of non-functional ACC and 19 cases(40.4%)of hypercortisolism(including 1 case of hypercortisolism combined with increased sex hormone secretion).Compared with non-functional group,hypercortisolism group had a significantly higher prevalence of hypertension(P=0.014),later ENSAT stage(P=0.010),and a higher proportion of hypervascularization(P=0.048).The median Ki-67 index was 20%(10%-40%),showing no significant correlation with either the maximum tumor diameter or SUVmax value,but it was related to ENSAT staging,with Ki-67 index in stageⅣ patients being significantly higher than that in stage Ⅱ(P=0.032).Immunohistochemistry results showed that the positive rate of Inhibin-α was 84.8%,and the positive rate of Melan-A was 40.9%.Conclusions ACC is a rare malignant endocrine tumor.ACC patients with hypercortisolism are more likely to be complicated with hypertension,have later staging,and more common hypervascular manifestations.Clinically,their endocrine function should be prioritized for assessment,and more active treatment strategies should be adopted.Diagnosis should be combined with imaging characteristics(such as hypervascularization)and immunohistochemical indicators(Ki-67,Inhibin-α,Melan-A).The significant increase in Ki-67 is in the advanced stage can serve as an important prognostic indicator to guide individualized treatment.
10.Frontal and Parietal Alpha Asymmetry as Biomarkers for Negative Symptoms in Schizophrenia
Yao-Cheng WU ; Chih-Chung HUANG ; Yi-Guang WANG ; Chu-Ya YANG ; Wei-Chou CHANG ; Chuan-Chia CHANG ; Hsin-An CHANG
Psychiatry Investigation 2025;22(4):435-441
Objective:
Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA).
Methods:
The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox.
Results:
Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%.
Conclusion
This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.


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