1.Akkermansia muciniphila-derived acetate activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis in metabolic-associated fatty liver disease.
Aoxiang ZHUGE ; Shengjie LI ; Shengyi HAN ; Yin YUAN ; Jian SHEN ; Wenrui WU ; Kaicen WANG ; Jiafeng XIA ; Qiangqiang WANG ; Yifeng GU ; Enguo CHEN ; Lanjuan LI
Acta Pharmaceutica Sinica B 2025;15(1):151-167
Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.
2.Intestinal metabolites in colitis-associated carcinogenesis: Building a bridge between host and microbiome.
Yating FAN ; Yang LI ; Xiangshuai GU ; Na CHEN ; Ye CHEN ; Chao FANG ; Ziqiang WANG ; Yuan YIN ; Hongxin DENG ; Lei DAI
Chinese Medical Journal 2025;138(16):1961-1972
Microbial-derived metabolites are important mediators of host-microbial interactions. In recent years, the role of intestinal microbial metabolites in colorectal cancer has attracted considerable attention. These metabolites, which can be derived from bacterial metabolism of dietary substrates, modification of host molecules such as bile acids, or directly from bacteria, strongly influence the progression of colitis-associated cancer (CAC) by regulating inflammation and immune response. Here, we review how microbiome metabolites short-chain fatty acids (SCFAs), secondary bile acids, polyamines, microbial tryptophan metabolites, and polyphenols are involved in the tumorigenesis and development of CAC through inflammation and immunity. Given the heated debate on the metabolites of microbiota in maintaining gut homeostasis, serving as tumor molecular markers, and affecting the efficacy of immune checkpoint inhibitors in recent years, strategies for the prevention and treatment of CAC by targeting intestinal microbial metabolites are also discussed in this review.
Humans
;
Gastrointestinal Microbiome/physiology*
;
Animals
;
Carcinogenesis/metabolism*
;
Colitis-Associated Neoplasms/microbiology*
;
Fatty Acids, Volatile/metabolism*
;
Bile Acids and Salts/metabolism*
;
Colitis/microbiology*
3.Novel autosomal dominant syndromic hearing loss caused by COL4A2 -related basement membrane dysfunction of cochlear capillaries and microcirculation disturbance.
Jinyuan YANG ; Ying MA ; Xue GAO ; Shiwei QIU ; Xiaoge LI ; Weihao ZHAO ; Yijin CHEN ; Guojie DONG ; Rongfeng LIN ; Gege WEI ; Huiyi NIE ; Haifeng FENG ; Xiaoning GU ; Bo GAO ; Pu DAI ; Yongyi YUAN
Chinese Medical Journal 2025;138(15):1888-1890
4.Effects of dapagliflozin on the risk of malignant ventricular arrhythmias in patients with acute myocardial infarction
Li DENG ; Ye DENG ; Qianwen CHEN ; Qingqing GU ; Qingjie WANG ; Yuan JI ; Ling SUN
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2025;32(1):31-36
Objective To investigate the effects of dapagliflozin on the risk of malignant ventricular arrhythmia(MVA)during hospitalization in patients with acute myocardial infarction(AMI).Methods A retrospective study was conducted to select patients with AMI who underwent percutaneous coronary intervention(PCI)in the department of cardiology of the Third Affiliated Hospital of Nanjing Medical University between January 2018 and November 2023.Clinical datas collected during hospitalization included demographics(gender,age),baseline vital signs(systolic blood pressure,diastolic blood pressure,heart rate),comorbidities(hypertension,diabetes mellitus),body mass index(BMI),smoking,alcohol consumption,ST segment elevation myocardial infarction(STEMI),Killip class≥3,laboratory parameters[white blood cell count(WBC),neutrophil percentage(NEU%),serum creatinine(SCr)],procedural data(number of coronary stents implanted,culprit vessels being the left main coronary artery,left anterior descending artery,right coronary artery,left circumflex artery and intraoperative hypotension),medications[angiotensin converting enzyme inhibitor/angiotensinⅡreceptor blocker(ACEI/ARB),β-blockers,aspirin,ticagrelor,clopidogrel,platelet glycoproteinⅡb/Ⅲa receptor antagonists,Statin],and electrocardiogram characteristics[the number of cases frequent ventricular premature contractions(premature beats)and the number of cases of sinus rhythm].The study endpoint was the occurrence of MVA during hospitalization among enrolled patients.Patients were categorized into the MVA group and the non-MVA group based on the occurrence of MVA during their hospital stay.Differences in clinical characteristics between the two groups were compared.Univariate and multivariate Logistic regression analyses were employed to evaluate the impact of dapagliflozin use on the risk of MVA in patients with AMI.Results A total of 2 893 eligible AMI patients were enrolled and 145 patients(5.01%)experienced MVA during hospitalization.Compared with the MVA group,the proportion of patients taking dapagliflozin was higher in the non-MVA group[13.2%(363/2 748)vs.6.2%(9/145),P=0.014],the proportion of males was higher[74.3%(2 042/2 748)vs.66.9%(97/145),P=0.048],the age was younger(years:64.82±13.91 vs.69.78±14.07,P<0.001),the heart rate at admission was slower(beats/min:80.09±15.72 vs.84.31±20.92,P=0.002),the proportion of patients with Killip grade≥3 was lower[11.5%(317/2 748)vs.38.6%(56/145),P<0.001],the proportion of smoking patients was higher[48.0%(1 319/2 748)vs.33.8%(49/145),P<0.05],SCr level was lower(μmol/L:84.73±58.52 vs.102.87±59.47,P<0.001),and the proportion of patients taking ACEI/ARB and β-blockers was higher[64.9%(1 783/2 748)vs.49.0%(71/145),65.1%(1 788/2 748)vs.53.8%(78/145),both P<0.05],the rate of frequent premature ventricular beats was lower[1.0%(28/2 748)vs.11.7%(17/145),P<0.05],and the proportion of patients with intraoperative hypotension was lower[3.2%(86/2 748)vs.10.6%(15/145),P<0.05].After adjusting numerous confounding factors,multifactorial Logistic regression analysis showed that dapagliflozin may significantly reduced the risk of MVA in patients with AMI after PCI[odds ratio(OR)=0.417,95%confidence interval(95%CI)was 0.200-0.880,P=0.022].Subgroup analysis suggested that there were 1 042 AMI patients with diabetes mellitus,of whom 348 took dapagliflozin,and 8 patients(2.30%)had MVA.The risk of MVA was reduced in patients taking dapagliflozin(Log-Rank:χ2=11.983,P=0.001).Conclusion The use of dapagliflozin significantly reduced the risk of MVA during hospitalization in patients with AMI.
5.Relationship between internal exposure levels and age and abnormal liver function in dimethylformamide exposed workers
Hongru GU ; Zhao LI ; Lei HAN ; Xin LIU ; Yuan ZHAO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(6):410-416
Objective:To explore the relationship between internal dimethylformamide (DMF) exposure levels and age and abnormal liver function in occupationally exposed workers, and to provide a reference for the prevention of DMF-induced toxicity.Methods:A total of 388 DMF exposed workers from 4 synthetic leather enterprises in Taicang City were selected by cluster sampling method from May to October 2024, and the data of occupational health examination and biological exposure indicators were collected. The relationship between N-methylcarbyl hemoglobin adduct (NMHb) and age and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT and gamma-glutamyl transpeptidyase (γ-GT) was analyzed by logistic regression, interaction effect analysis, and restricted cubic spline models.Results:The median age of 388 workers was 45.98 years old, the median concentration of NMHb was 165.50 nmol/g Hb, and the abnormal rate of liver function was 40.7% (158/388). NMHb and age of DMF-exposed workers were the influencing factors for liver dysfunction ( P<0.05), and the multiplicative interaction between the two was not statistically significant ( P=0.303), nor was the additive interaction statistically significant [relative excess risk due to interaction (RERI) =0.17 (95% CI: -2.35, 2.69), attributable proportion (AP) =0.03 (95% CI: -0.47, 0.54), synergy index (S) =1.04 (95% CI: 0.54, 2.02) ]. NMHb concentration was positively correlated with the abnormal risk of ALT, AST, AST/ALT, γ-GT and the concentration of ALT, AST, γ-GT ( Poverall <0.05, Pnonlinear>0.05), and negatively correlated with AST/ALT ( Poverall=0.032, Pnonlinear=0.781). Age was negatively correlated with abnormal risk of ALT, AST/ALT and ALT concentration ( Poverall<0.001, Pnonlinear>0.05), and positively correlated with AST/ALT ( Poverall=0.025, Pnonlinear=0.485) . Conclusion:There is a close relationship between NMHb and age of DMF-exposed workers and abnormal liver function. γ-GT can be used as a sensitive index, and special attention should be paid to the change of ALT index in elderly workers. Age should also be considered when AST/ALT is used as the screening indicator.
6.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
7.Correlation analysis of incidence trends of severe fever with thrombocytopenia syndrome (SFTS) and meteorological factors in Weifang city, Shandong province, 2015-2024
Ziliang FAN ; Xiyuan HUO ; Yaqi SHEN ; Cuimei GU ; Zhu YANG ; Senmei YUAN ; Miaomiao SHAN ; Jian ZHOU ; Ye ZHANG ; Dongying LI
Chinese Journal of Experimental and Clinical Virology 2025;39(2):154-161
Objective:To investigate the potential causes of the rising epidemic of severe fever with thrombocytopenia syndrome (SFTS) in Weifang, Shandong province.Methods:The temporal trend of SFTS epidemic was segmented using Joinpoint regression analysis. Changes in epidemiological characteristics across different periods were compared, and correlation analysis was conducted to identify meteorological factors influencing the epidemic trend.Results:Joinpoint regression revealed two distinct periods for SFTS epidemic in Weifang: 2015-2021 and 2022-2024. No significant trend was observed during 2015-2021 ( P=0.634), while a sharp annual increase of 46.69% occurred from 2022 to 2024 ( P=0.006). Spatial autocorrelation analysis demonstrated a global Moran’s I of 0.42 ( Z=8.55, P<0.001) for 2015-2021, with 15 high-high clustering areas identified. For 2022-2024, the global Moran’s I decreased to 0.37 ( Z=7.31, P<0.001), with 13 high-high clusters, including newly emerging hotspots in Anqiu and Zhucheng in the southeastern region. High-risk populations remained individuals aged ≥50 in mountainous and hilly areas, with a marked rise in incidence in these groups. The male-to-female ratio of cases was higher in plain areas than in mountainous/hilly regions. Autumn (September-November) temperatures from the preceding year showed a positive correlation with annual case numbers ( P=0.004, r=0.82). The linear regression expression is y=40.61x-580.78 (y is the annual incidence, and x is the average daily temperature of last autumn). Conclusions:The SFTS epidemic in Weifang is showing a rising trend. There is a linear correlation between the temperature of the previous autumn and the scale of SFTS epidemic in the following year. This correlation allows for predicting the subsequent year′s epidemic, thereby enabling early warning of SFTS.
8.Effect of early weight-bearing functional exercise on the postoperative function and satisfaction of patients with anterior talofibular ligament rupture
Hang WU ; Qiang LI ; Haitao YUAN ; Peng GU ; Shaoyong FAN ; Xiongwei DENG
China Modern Doctor 2025;63(28):5-8,57
Objective To explore the effect of early weight-bearing functional exercise on the postoperative function and satisfaction of patients with anterior talofibular ligament rupture.Methods Sixty patients with anterior talofibular ligament rupture admitted to Nanchang Hongdu Hospital of Traditional Chinese Medicine from June 2022 to June 2024 were included.According to the random number table method,the patients were divided into conventional group and early weight-bearing group,with 30 cases in each group.The American Orthopedic Foot and Ankle Society ankle-hindfoot scale(AOFAS-AHS)scores,Cumberland ankle instability tool(CAIT)scores,joint position sense active(JPSA)and joint position sense passive(JPSP)of ankle joint before and after the operation,and postoperative satisfaction of two groups of patients were compared.Results Six months after the operation,the AOFAS-AHS scores and CAIT scores of two groups were significantly higher than those before the operation,and the JPSA and JPSP were significantly lower than those before the operation(P<0.05).The AOFAS-AHS score and CAIT score of patients of early weight-bearing group were significantly higher than those of conventional group,while the JPSA and JPSP were significantly lower than those of conventional group(P<0.05).The satisfaction rate of patients of early weight-bearing group was significantly higher than that of conventional group(76.6%vs.66.6%,x2=6.205,P<0.001).Conclusion Early weight-bearing functional exercise can improve the postoperative function of patients with anterior talofibular ligament rupture and enhance their postoperative satisfaction.
9.Association relation of C0-C2 Cobb angle and cervical disc herniation.
Zhuo-Heng MAI ; Yuan-Li GU ; Hai-Ling WANG ; Li-Ying ZHANG ; Sheng-Qiang ZHANG
China Journal of Orthopaedics and Traumatology 2025;38(5):494-499
OBJECTIVE:
Objective To investigate the relationship between cervical disc herniation and C0-C2 Cobb angle.
METHODS:
The clinical data of 301 patients with cervical disc herniation from 2020 to 2024 were retrospectively analyzed. The median value of C0-C2 Cobb angle measurements from 301 patients was used as the boundary, cervical disc herniation patients were divided into two groups, C0-C2 Cobb angle <28.50 group and 151 patients with C0-C2 Cobb angle≥28.50 group. Among them, 150 patients in C0-C2 Cobb angle <28.50 group included 53 males and 97 females, aged 23 to 76 (57.32±12.55) years, with a disease duration of 7 to 19 (13.81±5.32) months;the othor 151 patients with C0-C2 Cobb angle≥28.50 group including 61 males and 90 females, aged 25 to 74 (56.86±12.51) years, with a disease duration of 8 to 18 (14.13±5.56) months. The cervical lordosis angle (C0-C2 Cobb angle and C2-C7 Cobb angle), T1 inclination slope (T1S) and cervical sagittal axial distance (C2-C7 SVA) were measured on the lateral cervical radiographs. The correlation between C0-C2 Cobb angle and cervical disc herniation range, protrusion position, average protrusion size and other parameters was analyzed.
RESULTS:
When the C0-C2 Cobb angle<28.50°, the average protrusion size was (2.21±0.56) mm, the C2-C7 Cobb angle was (19.92±12.06)° and the C2-C7 SVA was (1.10±1.20) mm. When the C0-C2 Cobb angle≥28.50°, the average protrusion size was (2.38±0.60) mm, the C2-C7 Cobb angle was (12.01±13.09 )°, the C2-C7 SVA was (1.53±1.36) mm, and the difference was statistically significant (P<0.05). Between the two groups of patients with C0-C2 Cobb angle < 28.50° and C0-C2 Cobb angle≥28.50°, there were significant differences in the size of C3,4, C4,5, C5,6, C6,7, C7, T1 disc herniation in single segment (P<0.05 ). C0-C2 Cobb angle was correlated with age(r=-0.135, P<0.05 ), C2-C7 Cobb angle (r=-0.382, P<0.01 ), C2-C7 SVA (r=0.293, P<0.01), average protrusion size (r=0.139, P<0.05), and the size of C3,4 (r=0.215, P<0.01 ), C4,5 (r=0.176, P<0.01 ), C5,6 (r=0.144, P<0.05 ), C6,7 (r=0.158, P<0.05 ), C7T1 (r=0.535, P<0.05) disc herniation.
CONCLUSION
There is a positive correlation between C0-C2 Cobb angle and the size of cervical disc herniation. C0-C2 Cobb angle can reflect the degree of cervical disc herniation. Previous studies have shown that the biomechanical changes between C0-C2 Cobb angle, C2-C7 Cobb angle, C2-C7 SVA and cervical extensor muscle group may be risk factors for accelerating cervical disc herniation and this may be one of the mechanisms that C0-C2 Cobb angle is positively correlated with the size of cervical disc herniation.
Humans
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Male
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Female
;
Middle Aged
;
Intervertebral Disc Displacement/physiopathology*
;
Adult
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Cervical Vertebrae/diagnostic imaging*
;
Aged
;
Retrospective Studies
;
Young Adult
10.Analysis of Hormone Levels in Patients with Hematological Diseases Before and After Hematopoietic Stem Cell Tansplantation.
Fen LI ; Yu-Jin LI ; Jie ZHAO ; Zhi-Xiang LU ; Xiao-Li GAO ; Hai-Tao HE ; Xue-Zhong GU ; Feng-Yu CHEN ; Hui-Yuan LI ; Qi SA ; Lin ZHANG ; Peng HU
Journal of Experimental Hematology 2025;33(5):1443-1452
OBJECTIVE:
By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage.
METHODS:
The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed.
RESULTS:
After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same.
CONCLUSION
HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans
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Hematopoietic Stem Cell Transplantation
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Female
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Male
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Hematologic Diseases/blood*
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Follicle Stimulating Hormone/blood*
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Triiodothyronine/blood*
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Luteinizing Hormone/blood*
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Thyroid Gland/metabolism*
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Estradiol/blood*
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Thyrotropin/blood*
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Gonads/metabolism*
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Adult
;
Middle Aged
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Adrenocorticotropic Hormone/blood*
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Hormones/metabolism*
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Adrenal Cortex/metabolism*
;
Prolactin

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