1.Necroptosis in Exercise-induced Skeletal Muscle Damage: Roles and Regulatory Mechanisms
Zhi-Fei KE ; Wen-Jing SONG ; Yun-Feng DONG ; Hua-Yu SHANG
Progress in Biochemistry and Biophysics 2026;53(7):1884-1895
Exercise-induced muscle damage (EIMD) is a frequent form of skeletal muscle microdamage that occurs after high-intensity, prolonged, or unaccustomed exercise, especially exercise dominated by eccentric contractions. It is commonly characterized by delayed-onset muscle soreness, transient loss of muscle strength, local inflammation, structural disruption of myofibers, and delayed functional recovery. Although mild EIMD may serve as a stimulus for training adaptation, excessive or insufficiently recovered muscle damage can impair exercise performance, disturb training continuity, and reduce participation in physical activity. Therefore, clarifying the molecular mechanisms that underlie the initiation, amplification, and resolution of EIMD is important for optimizing athletic training, improving post-exercise recovery, and guiding evidence-based public fitness practice. Necroptosis is a regulated form of programmed cell death mediated primarily by the receptor-interacting protein kinase (RIPK) 1/RIPK3/mixed lineage kinase domain-like protein (MLKL) signaling axis. Recent studies have shown that necroptosis is closely involved in tissue injury, sterile inflammation, and repair remodeling. However, whether necroptosis acts as an initiating driver, a secondary damage amplifier, or an adaptive signal required for repair after EIMD remains unclear. This review aimed to summarize the potential role of necroptosis in EIMD and to establish a mechanistic framework linking regulated cell death, inflammatory amplification, immune regulation, and skeletal muscle repair. Relevant studies concerning EIMD, necroptosis, RIPK1/RIPK3/MLKL signaling, damage-associated molecular patterns (DAMPs), inflammatory responses, immune cell recruitment, extracellular matrix remodeling, and muscle regeneration were reviewed and integrated. On this basis, the possible temporal and functional involvement of necroptosis in different phases of EIMD was analyzed. The main evidence summarized in this review suggests that EIMD is not merely a consequence of primary mechanical disruption. Instead, it develops through a dynamic sequence that includes sarcolemmal instability, calcium overload, mitochondrial dysfunction, oxidative stress, inflammatory mediator production, immune cell infiltration, necrotic tissue clearance, and regeneration-associated remodeling. Necroptosis may participate in this process through at least two interconnected mechanisms. First, in the early or progressive phase of EIMD, activation of the RIPK1/RIPK3/MLKL signaling axis may promote MLKL phosphorylation and plasma membrane permeabilization, leading to the release of DAMPs such as high-mobility group box 1, ATP, mitochondrial DNA, and other intracellular components. These signals may activate innate immune pathways, amplify inflammatory cytokine production, and enhance the recruitment of neutrophils and macrophages, thereby aggravating secondary inflammation and extending muscle fiber injury. Second, during the resolution and repair phases, necroptosis-related signaling may also contribute indirectly to the formation of a regenerative microenvironment. By influencing the clearance of necrotic debris, the recruitment and phenotypic transition of immune cells, and the remodeling of extracellular matrix components, necroptosis may affect satellite cell activation, myogenic repair, and the eventual structural and functional recovery of injured skeletal muscle. Thus, the biological effect of necroptosis in EIMD may be context dependent rather than uniformly harmful. Its outcome may depend on exercise intensity, the extent of tissue damage, the timing of pathway activation, the involved cell types, inflammatory status, training background, age, and metabolic condition. In conclusion, necroptosis may represent an important molecular link between skeletal muscle injury, sterile inflammation, and tissue repair after damaging exercise. It may exert a dual role in EIMD by amplifying secondary damage while also contributing to repair coordination under appropriate temporal and microenvironmental conditions. Future studies should determine the activation pattern of RIPK1/RIPK3/MLKL signaling after different exercise protocols, identify the major cell populations undergoing necroptosis in injured skeletal muscle, and examine whether targeted modulation of necroptosis can reduce excessive inflammation without impairing necessary regenerative responses. This review provides a theoretical basis for understanding the pathogenesis of EIMD and for developing targeted strategies to improve skeletal muscle recovery after exercise-induced injury.
2.Value of Golgi protein 73 in assessing liver fibrosis degree and prognosis of patients with resectable hepatocellular carcinoma
Wanying HUO ; Hua HE ; Xinyi YU ; Maiman HE ; Jing JIANG
Journal of Clinical Hepatology 2026;42(8):1878-1887
ObjectiveTo assess the performance of preoperative serum Golgi protein 73 (GP73) in diagnosing liver fibrosis degree in patients with resectable hepatocellular carcinoma (HCC), to investigate its value in predicting postoperative survival, and to provide a basis for risk stratification and individualized decision-making in this population. MethodsA total of 631 patients with HCC who underwent liver resection at The First Hospital of Jilin University from March 1, 2009 to December 31, 2022 were enrolled. The demographic, pathological, and serological features of the patients were collected, and the serum level of GP73 was measured before surgery. Scheuer score determined by liver biopsy was used as the gold standard for diagnosing liver fibrosis; the Spearman correlation analysis was used to investigate the correlation between GP73 and liver fibrosis; the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to assess the value of serum GP73 and compound serological markers in the diagnosis of liver fibrosis, and the Delong test was used for comparison of AUC. With all-cause mortality as the outcome, X-Tile 3.6.1 software was used to determine the optimal cut-off value of GP73; the univariate and multivariate Cox regression analyses were used to identify independent influencing factors for prognosis, and a nomogram model was constructed. Ten-fold cross-validation was used for internal validation; index of concordance (C-index), integrated discrimination improvement (IDI) index, and net reclassification improvement (NRI) index were calculated; calibration curve and decision curve analysis were used to assess the predictive performance of the model. ResultsThe serum level of GP73 was positively correlated with Scheuer liver fibrosis stage (rs=0.255, P<0.001). Serum GP73 had a significantly higher AUC than gamma-glutamyl transferase-to-platelet ratio (0.704 vs 0.634, Z=2.00, P=0.046) and S index (0.704 vs 0.637, Z=1.98, P=0.048) in the diagnosis of significant liver fibrosis, with no significant difference compared with aspartate aminotransferase-to-platelet ratio index (AUC=0.722) and fibrosis-4 index (AUC=0.695) (both P>0.05). During a median follow-up time of 48.66 months, 239 patients (37.9%) died. GP73 had an optimal cut-off value of 65 ng/mL in predicting postoperative mortality in patients with resectable HCC, and high GP73 expression (≥65 ng/mL) alone achieved a C-index of 0.617 for predicting the prognosis of HCC patients, which was better than the C-index of 0.551 for Barcelona Clinic Liver Cancer (BCLC) stage (P<0.001). The multivariate Cox regression analysis showed that serum GP73 (hazard ratio [HR]=2.56, 95% confidence interval [CI]: 1.86 — 3.52, P<0.001), sex (HR=1.58, 95%CI: 1.10 — 2.28, P=0.014), vascular invasion (HR=1.69, 95%CI: 1.30 — 2.21, P<0.001), total bilirubin (HR=1.49, 95%CI: 1.16 — 1.93, P=0.002), and maximum tumor diameter (HR=1.07, 95%CI: 1.04 — 1.11, P<0.001) were independent risk factors for all-cause mortality after hepatectomy in patients with HCC. In order to assess whether the addition of GP73 to the other four variables could further improve model performance, the model based on GP73, sex, vascular invasion, total bilirubin, and maximum tumor diameter was defined as the GP73-included model, and the model based on all five variables except GP73 was defined as the GP73-excluded model. The GP73-included model achieved an AUC of 0.704 (95%CI: 0.656 — 0.753) for predicting 5-year survival rate after surgery, and ten-fold cross-validation showed that this model had a mean C-index of 0.716 (95%CI: 0.682 — 0.750), which was higher than the C-index of the GP73-excluded model (C-index=0.682, 95%CI: 0.645 — 0.719, P=0.008) and BCLC stage (C-index=0.551, 95%CI: 0.523 — 0.580, P<0.001). Compared with the GP73-excluded model, the GP73-included model yielded an IDI index of 0.039 (95%CI: 0.016 — 0.069, P<0.001) and an NRI index of 0.259 (95%CI: 0.179 — 0.335, P<0.001), and compared with BCLC stage, the GP73-included model had an IDI index of 0.112 (95%CI: 0.069 — 0.163, P<0.001) and an NRI index of 0.272 (95%CI: 0.169 — 0.380, P<0.001). Calibration curve and decision curve analyses showed that the GP73-included model had good calibration and net clinical benefit. ConclusionGP73 can be used as a serological biomarker for diagnosing liver fibrosis in patients with resectable HCC, and preoperative GP73 level has a certain value in predicting the survival of these patients after hepatectomy. The integrated prognostic model incorporating GP73 can help to optimize postoperative risk stratification, thereby providing a basis for decision-making in precise treatment of HCC.
3.Controllability Analysis of Structural Brain Networks in Young Smokers
Jing-Jing DING ; Fang DONG ; Hong-De WANG ; Kai YUAN ; Yong-Xin CHENG ; Juan WANG ; Yu-Xin MA ; Ting XUE ; Da-Hua YU
Progress in Biochemistry and Biophysics 2025;52(1):182-193
ObjectiveThe controllability changes of structural brain network were explored based on the control and brain network theory in young smokers, this may reveal that the controllability indicators can serve as a powerful factor to predict the sleep status in young smokers. MethodsFifty young smokers and 51 healthy controls from Inner Mongolia University of Science and Technology were enrolled. Diffusion tensor imaging (DTI) was used to construct structural brain network based on fractional anisotropy (FA) weight matrix. According to the control and brain network theory, the average controllability and the modal controllability were calculated. Two-sample t-test was used to compare the differences between the groups and Pearson correlation analysis to examine the correlation between significant average controllability and modal controllability with Fagerström Test of Nicotine Dependence (FTND) in young smokers. The nodes with the controllability score in the top 10% were selected as the super-controllers. Finally, we used BP neural network to predict the Pittsburgh Sleep Quality Index (PSQI) in young smokers. ResultsThe average controllability of dorsolateral superior frontal gyrus, supplementary motor area, lenticular nucleus putamen, and lenticular nucleus pallidum, and the modal controllability of orbital inferior frontal gyrus, supplementary motor area, gyrus rectus, and posterior cingulate gyrus in the young smokers’ group, were all significantly different from those of the healthy controls group (P<0.05). The average controllability of the right supplementary motor area (SMA.R) in the young smokers group was positively correlated with FTND (r=0.393 0, P=0.004 8), while modal controllability was negatively correlated with FTND (r=-0.330 1, P=0.019 2). ConclusionThe controllability of structural brain network in young smokers is abnormal. which may serve as an indicator to predict sleep condition. It may provide the imaging evidence for evaluating the cognitive function impairment in young smokers.
4.Cloning, subcellular localization and expression analysis of SmIAA7 gene from Salvia miltiorrhiza
Yu-ying HUANG ; Ying CHEN ; Bao-wei WANG ; Fan-yuan GUAN ; Yu-yan ZHENG ; Jing FAN ; Jin-ling WANG ; Xiu-hua HU ; Xiao-hui WANG
Acta Pharmaceutica Sinica 2025;60(2):514-525
The auxin/indole-3-acetic acid (Aux/IAA) gene family is an important regulator for plant growth hormone signaling, involved in plant growth, development, as well as response to environmental stresses. In the present study, we identified
5.Quality evaluation of Gegen Formula Granules
Dai-liang ZHANG ; Chun-xia WANG ; Lei SHI ; Yu-kang LIU ; Yong-qiang LIN ; Yu-zhuo WANG ; Jing-hua ZHANG ; Jin-xin LI ; Gui-yun CAO ; Zhao-qing MENG
Chinese Traditional Patent Medicine 2025;47(5):1421-1431
AIM To evaluate the quality of Gegen Formula Granules.METHODS Linear calibration with two reference substances(LCTRS)was adopted in the predicting of retention time with puerarin and daidzein as internal standards.UPLC characteristic chromatograms were established.The contents of 3'-hydroxy puerarin,puerarin(internal standard),3'-methoxy puerarin,puerarin 6"-O-xyloside,puerarin apioside and daidzin were determined by quantitative determination analysis multi-components by a single marker(QAMS),after which their transfer rates were calculated.RESULTS Compared with relative retention time method,LCTRS demonstrated higher positional accuracy for characteristic peaks and wider application range for columns.There were 9 characteristic peaks in the characteristic chromatograms for 14 batches of formula granules and 15 batches of standard decoctions with the similarities of more than 0.95.The contents and transfer rates of various constituents in formula granules and standard decoctions were basically consistent.CONCLUSION The chemical constituents in formula granules and their standard decoctions of Puerariae lobatae Radix display good consistency,reliable preparation process is observable in the former.
6.Comparative analysis of autogenous arteriovenous fistula versus arteriovenous graft in maintenance hemodialysis patients
Weiping YU ; Hua JIANG ; Xiping MA ; Yumeng QIAN ; Xueping YE ; Jing YUAN
Chinese Journal of Nephrology 2025;41(3):183-188
Objective:To compare the application effects of upper arm autogenous arteriovenous fistula (AVF) and forearm arteriovenous graft (AVG) in maintenance hemodialysis (MHD) patients, and to analyze the factors influencing the long-term patency rate of arteriovenous fistulas in MHD patients.Methods:It was a retrospective cohort study. The data of MHD patients treated in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2021 to May 2023 was collected. Participants were stratified into two groups: forearm AVG and upper arm AVF. The parameters including urea clearance index (Kt/V), serum C-reactive protein (CRP), albumin levels, access-related costs, complication rates, and long-term primary patency were compared. The end event was defined as arteriovenous fistula failure, that was, the arteriovenous fistula could not be used for dialysis puncture, or the arteriovenous fistula lost function after adequate blood flow was achieved. Kaplan-Meier survival curves with log-rank tests were employed to compare access survival, while multivariable Cox regression was used to analyze the independent associated factors of patency.Results:A total of 71 MHD patients were enrolled in this study, including 35 males, with age of (64.9±11.7) years and fistula establishment time of 30.0(17.0, 58.0) months. There were 32 cases (45.1%) in the forearm AVG group and 39 cases (54.9%) in the upper arm AVF group. Compared with the forearm AVG group, the upper arm AVF group had higher serum albumin levels [38.9 (37.0, 42.1) g/L vs. 38.0 (34.6, 40.0) g/L, Z=-2.364, P=0.018], higher pain scores [3.0(2.0, 5.0) points vs. 2.0(1.0, 3.0) points, Z=-3.012, P=0.003], and higher long-term patency rates of arteriovenous fistulas (at 3, 6, 12, and 24 months, all P<0.01), while the complication rate[61.5% (24/39) vs. 93.7% (30/32), χ2=10.015, P=0.002], the cost of the access [0 (0, 9,117.0) yuan·year -1·person -1vs. 10 380.5 (7 186.0, 30 228.5) yuan·year -1·person -1, Z=-4.094, P<0.001] were lower, and the length of the available puncture vessel segment was shorter [3.5(3.0, 5.0) cm vs. 6.5(6.0, 8.0) cm, Z=-6.477, P<0.001].The Kaplan-Meier survival analysis results showed that the primary patency rate of the upper arm AVF group was significantly higher than that of the forearm AVG group (Log-rank test, χ2=23.690, P<0.001). The multivariate Cox regression analysis results indicated that the type of fistula being forearm AVG (with upper arm AVF as reference, HR=4.907, 95% CI 1.740-13.840) and increased complications number ( HR=1.234, 95% CI 1.040-1.464) were the independent factors promoting the arteriovenous fistula failure in MHD patients. Conclusions:The type of internal fistula and the complications are the factors affecting the long-term patency rate of internal fistula in MHD patients.Upper arm AVF offers cost-effectiveness and sustained patency advantages over forearm AVG but requires careful consideration of puncture challenges and patient discomfort. Individualized access selection should balance anatomical constraints with clinical priorities.
7.Endometriosis-associated ovarian mesonephric-like adenocarcinoma:a clinicopathological analysis of 9 cases
Hua WANG ; Jing LIU ; Yu CHENG ; Shunni WANG ; Fangfang ZHONG ; Weiyong GU
Chinese Journal of Obstetrics and Gynecology 2025;60(6):469-476
Objective:To investigate the clinical and pathological characteristics, treatment and prognosis of endometriosis (EM)-associated ovarian mesonephric-like adenocarcinoma (MLA).Methods:Clinical and pathological data were collected from nine patients diagnosed with EM-associated ovarian MLA at the Obstetrics and Gynecology Hospital of Fudan University between January 2022 and December 2024. Histological slides were re-reviewed, immunohistochemical examination and molecular testing were performed, and patient follow-up was conducted.Results:(1) Clinical characteristics: the median age of the nine patients was 54 years (range: 38-69 years). All patients presented with a pelvic mass; five cases also reported abdominal pain. Tumor location included five cases in the right ovary, two in the left ovary, and two involving both ovaries. International Federation of Gynecology and Obstetrics (FIGO) staging showed 3 cases at stage Ⅰ, 4 at stage Ⅱ, and 2 at stage Ⅲ. (2) Pathological features: gross examination revealed mixed solid-cystic masses with solid areas appearing gray-white or yellow-brown; the median maximum tumor diameter was 9.0 cm (range: 2.6-13.0 cm). Microscopically, tumors exhibited various architectural patterns, including tubular, glandular, papillary, slit-like, sex cord-like, glomeruloid, and solid structures, with tubular and glandular patterns being most common. Tumor cells demonstrated mild to moderate nuclear atypia. Of the 11 tumor foci in the 9 cases, 8 showed coexistence of MLA with other tumor components, such as endometrioid carcinoma, borderline endometrioid or borderline seromucinous tumors. In 1 case of MLA mixed with a borderline endometrioid tumor, both components exhibited squamous metaplasia. Immunohistochemistry showed variable expression of GATA-binding protein 3, thyroid transcription factor-1, CD 10, and calretinin, with positive rates of 9/11, 8/11, 5/11, and 3/6, respectively. Two tumor foci (2/11) exhibited focal expression of estrogen receptor and progesterone receptor. All cases displayed wild-type p53 expression. Molecular testing via next-generation sequencing in five patients revealed pathogenic mutations in the KRAS gene (5/5), with 3 cases (3/5) harboring additional pathogenic mutations in other genes. (3) Treatment and prognosis: all patients underwent surgery, supplemented by chemotherapy and (or) targeted therapy. Five patients underwent comprehensive staging surgery, four received cytoreductive surgery, and one patient received targeted therapy. The median follow-up duration was 7 months (range: 2-27 months). Three patients (3/9) experienced recurrence, and no deaths were reported during the follow-up period. Conclusions:EM-associated ovarian MLA demonstrates diverse morphological patterns and frequently coexists with other tumor types. Accurate diagnosis relies on an integrated evaluation of histomorphology, immunohistochemistry, and molecular testing. The primary treatment for EM-associated ovarian MLA is surgery, followed by adjuvant chemotherapy. Patients harboring pathogenic KRAS p.G12C mutations may benefit from targeted therapies. Ovarian MLA is an aggressive tumor, prone to recurrence in the short term, and has a poor prognosis.
8.The efficacy of blinatumomab in the treatment of pediatric B-cell acute lymphoblastic leukemia: a multicenter study
Weiling YAN ; Jun LU ; Hua WANG ; Lihua YU ; Huidi FENG ; Bai LI ; Wenguang JIA ; Jian WANG ; Wenting HU ; Xue TANG ; Jing FAN ; Yujie GUAN ; Xiaolan LI ; Yalan YOU ; Yongmin TANG ; Xiaojun XU
Chinese Journal of Pediatrics 2025;63(11):1194-1200
Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.
9.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.
10.Characteristics analysis of multimodal metabolic disorders in subclinical Cushing's syndrome patients with different cortisol levels
Ya-Jing WANG ; Bing LI ; Huai-Jin XU ; Qi NI ; Ya-Qi YIN ; Yi-Jun LI ; Li ZANG ; Yu CHENG ; Kang CHEN ; 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):793-799
Objective To characterize multimodal metabolic disorders in subclinical Cushing's syndrome(SCS)patients with different cortisol levels,providing a reference for clinical diagnosis and treatment.Methods A retrospective analysis was conducted on the clinical data of 165 SCS patients diagnosed at the First Medical Center of Chinese PLA General Hospital due to adrenal masses from January 2014 to October 2024.Using the serum cortisol levels after the midnight 1 mg dexamethasone suppression test(1 mg DST)as the cut-off point,SCS patients were divided into high-level group(1 mg DST-F>138 nmol/L,n=96)and low-level group(50 nmol/L<1 mg DST-F≤138 nmol/L,n=69).The differences in age,gender,body mass index(BMI),blood pressure,glucolipid metabolism indices,electrolytes,hormone levels,and imaging features of adrenal adenoma(such as CT values)were compared between the two groups.Multivariate linear regression was used to analyze the correlation between CT values and metabolic indices.Results Compared with low-level group,patients in high-level group were younger(54.0±11.3 vs.57.7±10.3,P=0.034),while there were no statistically significant differences in gender ratio or BMI between the two groups(P>0.05).Both groups exhibited decreased adrenocorticotropic hormone(ACTH)levels and disrupted circadian rhythm.Compared with low-level group,high-level group showed significantly higher F0:00 levels[250.00(170.07,422.53)nmol/L vs.110.00(82.74,133.90)nmol/L]and 24-hour urinary free cortisol(24 h UFC)[568.40(377.80,875.45)nmol/24 h vs.369.40(265.40,494.69)nmol/24 h](P<0.001),with no significant differences in serum F8:00,or 1 mg DST ACTH0:00 levels(P>0.05).Except for the fasting C-peptide level in the high-level group being higher than that in low-level group[(2.88±1.01)ng/ml vs.(2.46±0.78)ng/ml,P=0.024],there were no significant differences in blood pressure,blood lipids,glycated hemoglobin(HbA1c),fasting blood glucose,fasting insulin,serum electrolytes,uric acid,and other indices between the two groups(P>0.05).The CT value of adrenal adenoma during contrast-enhanced scanning was higher in high-level group[80.00(17.80,93.00)Hu vs.52.00(35.50,75.00)Hu,P=0.006]compared with low-level group.Multivariate linear regression analysis revealed that diastolic blood pressure was positively correlated with CT values of adrenal adenomas in both plain scanning(β=0.49,95%CI 0.09-0.90)and contrast-enhanced scanning(β=2.08,95%CI 0.76-3.39),while triglyceride levels were negatively correlated with plain scanning CT values(β=-5.77,95%CI-10.88--0.66).Conclusion Patients with SCS at different cortisol levels differ in age,fasting C-peptide levels,and CT values.CT values may serve as potential imaging markers to assess metabolic risk in SCS patients.

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