1.Mechanism of Bushen Kaixuan Tongluo Prescription in Improving Diabetic Nephropathy Based on cAMP Signaling Pathway
Miao XU ; Baosheng ZHAO ; You WANG ; Yuzhuo CHANG ; Zehao LIU ; Lingling QIN ; Haiyan WANG ; Ming GAO ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):87-96
ObjectiveTo investigate the molecular mechanism by which the Bushen Kaixuan Tongluo prescription exerts a renal protective effect in mice with diabetic kidney disease (DKD) by regulating the cyclic adenosine monophosphate (cAMP) signaling pathway. MethodsThirty specific pathogen-free (SPF) male db/db mice were adaptively fed for three weeks. Mice with a random tail vein blood glucose level ≥ 11.1 mmol·L-1 and urinary albumin-creatinine ratio (ACR) ≥ 30 mg·g-1 were considered successfully modeled. The successfully modeled mice were randomly divided into five groups with six mice in each group: the model group, the low-, medium-, and high-dose Bushen Kaixuan Tongluo prescription groups (administered at doses of 7, 14, 28 g·kg-1·d-1 respectively), and the positive drug irbesartan group (administered at a dose of 20 mg·kg-1·d-1). Additionally, six db/m mice were selected as the blank group. Mice in each group were given intragastric administration of the Bushen Kaixuan Tongluo prescription at the corresponding concentrations, irbesartan, or an equal volume of pure water, and the intervention lasted for 12 weeks. During the experiment, the general conditions, body weight changes, and renal function indicators of the mice were dynamically monitored. After the intervention, a blood glucose meter was used to measure the fasting blood glucose (FBG) of the mice. An automatic biochemical analyzer was employed to detect the levels of serum creatinine (SCr), blood urea nitrogen (BUN), urinary microalbumin (uALB), ACR, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglycerides (TG), leptin (LEP), glycosylated serum protein (GSP), and insulin (INS) in the mice. Renal tissues were collected for hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and Masson's trichrome staining to observe the histopathological changes. Immunohistochemistry (IHC) was used to detect the expressions of protein kinase A (PKA) and cAMP response element-binding protein (CREB) in the mice. Western blot analysis was performed to determine the expression levels of PKA, phosphorylated protein kinase A (p-PKA), CREB, phosphorylated cAMP response element-binding protein (p-CREB), and B-cell lymphoma-2 (Bcl-2) proteins in the renal tissues of the mice. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of PKA, CREB, and Bcl-2 in the renal tissues of the mice. ResultsCompared with the blank group, the mice in the model group showed listlessness, decreased activity, and a significant increase in body weight (P<0.01). Biochemical indicators revealed that the levels of BUN, uALB, ACR, AST, ALT, TC, TG, FBG, LEP, GSP, and INS were significantly increased (P<0.01), while SCr showed an increasing trend with no statistically significant difference. Compared with the model group, the mice in the Bushen Kaixuan Tongluo prescription intervention groups had improved general conditions and a decreasing trend in body weight. Biochemical indicators showed that the levels of BUN, uALB, ACR, TC, GSP, and INS were significantly decreased (P<0.05), while SCr, AST, ALT, TG, and LEP showed a decreasing trend with no statistically significant difference. Renal histopathological analysis showed that the model group exhibited typical DKD pathological features such as thickening of the glomerular basement membrane, expansion of the mesangial matrix, and deposition of collagen fibers in the renal tubulointerstitium, and all treatment groups could alleviate the above pathological damages. The IHC results showed that compared with the blank group, the expression levels of p-PKA and p-CREB in the renal tissues of the model group were significantly decreased (P<0.01). Compared with the model group, the expression level of p-PKA in the medium-dose Bushen Kaixuan Tongluo prescription group was significantly increased (P<0.01), while the expression level of p-CREB showed an increasing trend with no statistically significant difference. Western blot results showed that compared with the blank group, the expression levels of p-PKA/PKA, p-CREB/CREB, and Bcl-2 in the model group were significantly decreased (P<0.05). Compared with the model group, the expression levels of these proteins in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly increased (P<0.01). Real-time PCR results showed that compared with the blank group, the mRNA expressions of PKA, CREB, and Bcl-2 in the model group were significantly down-regulated (P<0.05). Compared with the model group, the mRNA expressions of these genes in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly up-regulated (P<0.05). ConclusionThe Bushen Kaixuan Tongluo prescription can improve the liver and kidney functions of db/db mice, correct lipid metabolism disorders and glucose metabolism imbalance. Its renal protective effect is associated with up-regulating the cAMP signaling pathway to improve renal fibrosis and reduce the level of oxidative stress, thereby protecting renal function.
2.Incentive and constraint factors and optimization strategies for artificial intelligence application in pharmacy based on TAM-TOE-DOI integrated framework
Jian YANG ; Zhichu LI ; Weili ZHAO ; Xiaoyi YU ; Ming XU
China Pharmacy 2026;37(11):1478-1484
OBJECTIVE Identify the incentive and constraint factors of artificial intelligence (AI) application in the pharmaceutical field, and promote the application of AI in the field of pharmacy. METHODS Based on the technology acceptance model (TAM), technology-organization-environment (TOE) framework, and diffusion of innovation theory (DOI), a TAM-TOE-DOI integrated framework was constructed through a four-stage research process of “theoretical review → dimension mapping → mechanism integration → proposition development”. Combining the analytical pathways of the above three theories in AI application in pharmacy with the integration mechanisms and core propositions of the TAM-TOE-DOI, literature review and deductive reasoning were employed to systematically identify the incentive and constraint factors of AI application in pharmacy from three levels:micro (TAM), meso (TOE), and macro (DOI), and to propose optimization strategies. RESULTS & CONCLUSIONS At the micro level, the efficiency transformation and quality improvement brought by AI technology were the main incentive factors for perceived usefulness, while technological complexity and algorithmic opacity were the main constraint factors for perceived ease of use. At the meso level, the completeness of technological infrastructure, the strength of top management support and innovation climate, as well as external institutional pressure and competitive driving forces were the core incentive factors, whereas scarcity of organizational resources and talent shortage were the main constraint factors. At the macro level, relative advantage and observability were typical incentive factors, while technological complexity was a typical constraint factor. China’s health administration, medical insurance authorities, and other relevant departments should coordinate efforts at the macro, meso, and micro levels to advance AI application in pharmacy: optimizing human-computer interaction and implementing tiered training programs at the micro level; reinforcing organizational support systems and capacity building at the meso level; dismantling data barriers and building social trust at the macro level. Differentiated implementation pathways should be developed for medical institutions at different tiers.
3.Proteomic Profiling of Qi-blood Deficiency vs Damp-heat Syndrome in Colorectal Cancer: Therapeutic Targeting by Astragaloside IV-berberine
Zhao-Huan LI ; Jing-Wen ZHAO ; Xin ZHANG ; Jian-Jin GUO ; Jie XU ; Zeng-Qiang YANG ; Hao TU ; Min ZOU ; Ming-Bin GUI ; Feng GAO
Progress in Biochemistry and Biophysics 2026;53(9):2462-2479
ObjectiveColorectal cancer (CRC) is a highly heterogeneous malignancy, and traditional Chinese medicine (TCM) syndrome differentiation is widely used in its clinical management. However, the biological basis underlying different TCM syndromes remains insufficiently understood. This study aimed to investigate the proteomic differences between qi-blood deficiency syndrome (QBDS) and damp-heat syndrome (DHS) in CRC patients and to establish a “syndrome-differential protein-herbal component” network for exploring potential molecular mechanisms and therapeutic targets associated with syndrome-specific treatment strategies. MethodsTumor tissue samples were collected from 10 patients with pathologically confirmed CRC, including 5 patients diagnosed with QBDS and 5 with DHS according to standardized TCM syndrome differentiation criteria. Tandem mass tag (TMT)-based quantitative proteomics was employed to identify differentially expressed proteins (DEPs) between the two syndrome groups. Functional enrichment analyses, including Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were performed to characterize the biological functions and signaling pathways associated with the identified DEPs. Least absolute shrinkage and selection operator (LASSO) regression analysis was further applied to screen key syndrome-related proteins and construct a core protein prediction model. Subsequently, molecular docking was conducted to evaluate the binding affinities between representative herbal compounds, astragaloside IV and berberine, and the identified core proteins. Finally, cell counting kit-8 (CCK-8) assays were performed in HCT 116 and HT-29 colorectal cancer cell lines to validate the anti-proliferative activities of these compounds in vitro. ResultsA total of 44 DEPs were identified between QBDS and DHS tissues, including 21 upregulated and 23 downregulated proteins in the QBDS group relative to the DHS group. Functional enrichment analyses revealed that these proteins were primarily associated with antiviral immune responses, regulation of inflammatory signaling, NF‑κB signaling pathways, cholesterol metabolism, and other biological processes relevant to tumor progression and host immune regulation. LASSO regression analysis identified eight core proteins with potential syndrome-specific significance. Among them, ST7, GPCPD1, and PODXL were closely associated with QBDS, whereas FAT1, GRB7, KRT7, MAFF, and MMP8 were associated with DHS. Molecular docking demonstrated favorable interactions between astragaloside IV and QBDS-related proteins, with binding energies lower than -5 kcal/mol, indicating stable binding activity. Berberine exhibited even lower binding energies and stronger binding specificity toward DHS-related core proteins. In vitro experiments further confirmed that both compounds inhibited CRC cell proliferation, while berberine displayed significantly greater anti-proliferative efficacy. The lowest 48 h IC50 value of berberine reached 15.21 mg/L in CRC cells, indicating a stronger growth-inhibitory effect than astragaloside IV. ConclusionCRC patients with QBDS and DHS exhibit distinct proteomic characteristics, suggesting that different TCM syndromes possess unique molecular signatures. The identified core proteins may serve as potential biomarkers for syndrome differentiation, while astragaloside IV and berberine may exert therapeutic effects through targeting syndrome-specific molecular networks. These findings provide preliminary proteomic evidence supporting syndrome-guided precision integrative medicine in CRC and offer new insights into the biological basis of TCM syndrome differentiation and individualized therapeutic strategies.
4.Research and Application of Scalp Surface Laplacian Technique
Rui-Xin LUO ; Si-Ying GUO ; Xin-Yi LI ; Yu-He ZHAO ; Chun-Hou ZHENG ; Min-Peng XU ; Dong MING
Progress in Biochemistry and Biophysics 2025;52(2):425-438
Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.
5.A multicenter clinical study on intramedullary vancomycin injection for preventing periprosthetic joint infection in total knee arthroplasty
Te LIU ; Jun FU ; Shiguang LAI ; Zhuo ZHANG ; Chi XU ; Lei GENG ; Yang LUO ; Peng REN ; Xin ZHI ; Quanbo JI ; Heng ZHANG ; Runkai ZHAO ; Haichao REN ; Ye TAO ; Qingyuan ZHENG ; Zeyu FENG ; Jianfeng YANG ; Yiming WANG ; Pengcheng LI ; Shuai LIU ; Wei CHAI ; Xiang LI ; Huiwu LI ; Xiaogang ZHANG ; Baochao JI ; Xianzhe LIU ; Xinzhan MAO ; Jianbing MA ; Xiangxiang SUN ; Jiying CHEN ; Yonggang ZHOU ; Jinliang WANG ; Weijun WANG ; Guoqiang ZHANG ; Ming NI
Chinese Journal of Orthopaedics 2025;45(12):803-811
Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.
6.Clinical characteristics and prognosis analysis of Crohn's disease complicated with secondary upper gastrointestinal fistulas
Jie XU ; Ming DUAN ; Jiajia ZHAO ; Yi LI ; Weiming ZHU
Chinese Journal of Inflammatory Bowel Diseases 2025;09(4):303-309
Objective:To evaluate the clinical characteristics of Crohn's disease (CD) patients with secondary upper gastrointestinal fistulas and analyze risk factors for recurrence.Methods:A restrospective observational research method was performed. Clinical data of CD patients with secondary upper gastrointestinal fistulas treated at Eastern Theater General Hospital of PLA from January 2010 to August 2024 were analyzed. Based on postoperative recurrence of upper gastrointestinal fistulas, the patients were divided into recurrence group and non-recurrence group. Differences in clinical data between the two groups were compared, and further multivariate Logistic regression analysis was used to identify the risk factors for fistula recurrence.Results:A total of 72 CD patients with secondary upper gastrointestinal fistulas were included, consisting of 48 males and 24 females, with a mean age of 39±12 years and a disease duration of 97±56 months, accounting for 2.8% of all CD patients undergoing surgeries during the same period. Among these patients, 75 upper gastrointestinal fistulas from 72 patients were identified, including 67 patients of simple duodenal fistula, 2 of simple gastric fistula, and 3 of double fistulas (2 of double duodenal fistulas and 1 of duodenal fistula combined with gastric fistula) .The preoperative diagnostic positivity rates were 55.6% (40/72) for gastroscopy, 54.2% (39/72) for upper gastrointestinal contrast imaging, 22.2% (16/72) for abdominal CT, and 22.2% (16/72) for colonoscopy. A history of biologic therapy was present in 33.3% (24/72) of patients, but none achieved fistula healing. All 72 patients underwent surgical treatment, with primary lesion surgical approaches including resection with anastomosis (37 patients, 51.4%) and resection with stoma (35 patients, 48.6%). Except for one gastric fistula treated by resection, all other fistulas underwent primary repair. During a median follow-up of 69 (40, 113) months, 8 patients (11.1%) required reoperation due to recurrent upper gastrointestinal fistulas (classified as the recurrence group), while the remaining 64 patients were assigned to the non-recurrence group. Univariate analysis revealed that the recurrence group had a higher proportion of patients aged 30-40 years ( P = 0.003), malnutrition ( P = 0.040), and anastomosis near the duodenum ( P = 0.047), but a lower proportion of postoperative biologic use ( P = 0.007) .Multivariate Logistic regression analysis showed that malnutrition and anastomosis near the duodenum were not the risk factors for duodenal fistula recurrence (both P > 0.05) . Conclusions:Upper gastrointestinal fistulas secondary to CD are rare, predominantly presenting as simple duodenal fistulas. Diagnosis primarily relies on gastroscopy and gastrointestinal contrast imaging. Biologic therapy shows poor efficacy, and most patients do not recur after the primary repair surgery of duodenal fistulas.
7.Research progress on correlation of non-steroidal anti-inflammatory drugs and bone stress injury
Ning QIANG ; Jin WANG ; Jian YU ; Jin-Fang XU ; Ming-Xin WANG ; Chen-Hui DONG ; Shen-Song LI ; Jin ZHAO ; Chun-Bao LI
Medical Journal of Chinese People's Liberation Army 2025;50(3):341-350
Non-steroidal anti-inflammatory drugs(NSAIDs),commonly utilized analgesics,are extensively employed for managing pain associated with musculoskeletal disorders or injuries.Recent clinical studies have demonstrated a heightened risk of bone stress injuries(BSI)in soldiers and athletes,particularly during high-intensity training,due to NSAID usage.Furthermore,the impact of NSAIDs on fracture healing is well-documented;however,the precise mechanism by which their use during training contributes to an increased incidence of stress bone injuries remains unclear.This article aims to summarize potential mechanisms through an extensive review of domestic and international literature in order to standardize the utilization and clinical management of NSAIDs,optimize pain management strategies,and prevent stress bone injuries or fractures in specific populations such as soldiers and elite athletes.
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.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.
10.Clinical characteristics of clinical and subclinical Cushing's syndrome caused by primary bilateral macronodular adrenal hyperplasia
Huai-Jin XU ; Bing LI ; Kang CHEN ; Hui-Xin ZHOU ; Ya-Jing WANG ; Li ZANG ; Xian-Ling WANG ; Yu CHENG ; Jin DU ; Qing-Hua GUO ; Wei-Jun GU ; Zhao-Hui LYU ; Jian-Ming BA ; Jing-Tao DOU ; Yi-Ming MU
Medical Journal of Chinese People's Liberation Army 2025;50(7):800-807
Objective To investigate the clinical characteristics of patients with clinical and subclinical Cushing's syndrome caused by primary bilateral macronodular adrenal hyperplasia(PBMAH).Methods A retrospective analysis was performed on the clinical data of 198 patients with Cushing's syndrome caused by PBMAH diagnosed in the First Medical Center of Chinese PLA General Hospital from January 2004 to October 2024.According to clinical manifestations,the patients were classified into clinical type Cushing's syndrome(n=61)and subclinical type Cushing's syndrome(n=137),and the clinical characteristics of the two types were compared.Results The mean age at diagnosis of patients with PBMAH-induced Cushing's syndrome was(53.5±10.4)years,including 118 males and 80 females,with a male-to-female ratio of 1.475:1.Compared with the subclinical type,the clinical type had a higher proportion of females,higher levels of serum cortisol,24-hour urine free cortisol(24 h UFC),and inhibited serum cortisol after low-dose dexamethasone suppression.Additionally,the clinical type had lower plasma ACTH,larger adrenal nodules and a higher risk of surgery(P<0.05)compared with those in subclinical type.The incidences of hypertension,dyslipidemia,obesity,diabetes mellitus,hypokalemia,vitamin D deficiency,osteoporosis,coronary heart disease,and cerebrovascular disease in patients with Cushing's syndrome caused by PBMAH were 87.9%,50.5%,37.1%,36.9%,27.8%,25.9%,18.7%,18.7%and 12.1%,respectively.Among them,compared with subclinical type patients,clinical type patients had higher incidence of hypokalaemia,vitamin D deficiency and osteoporosis(P<0.05),while there were no statistically significant differences in the incidences of other comorbidities between the two types(P>0.05).The results of postoperative follow-up for PBMAH patients showed that the short-term biochemical remission rate of unilateral total adrenalectomy was 41.5%(22/53)and the long-term biochemical remission rate was 32.0%(8/25).The short-term biochemical remission rate of unilateral partial(or nodular)adrenalectomy was 52.9%(9/17),and the long-term biochemical remission rate was 14.3%(1/7).All patients who underwent unilateral total adrenalectomy plus contralateral partial resection developed adrenal insufficiency(3/3),and 1 patient(1/3)relapsed 3.4 years after surgery.Conclusion Clinical and subclinical types of Cushing's syndrome caused by PBMAH have their distinct clinical characteristics.Surgery is an effective treatment for PBMAH,but a certain proportion of patients fail to achieve biochemical remission after non-bilateral total adrenalectomy.

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