OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

Objective To investigate the metabolic characteristics of patients with early-onset type 2 diabetes mellitus(T2DM)and to develop a risk prediction model for microvascular complications.Methods A retrospective study was conducted on 980 T2DM patients admitted for treatment between April 2020 and April 2024.Based on age at diagnosis,the patients were divided into two groups,an early-onset T2DM group(age at diagnosis<40 years,n=265)and a late-onset T2DM group(age at diagnosis≥40 years,n=715).Differences in metabolic indicators between the two groups were compared.Patients in the early-onset group were further divided into a complication subgroup(n=142)and a non-complication subgroup(n=123)based on the presence or absence of microvascular complications.Data on baseline characteristics,metabolic parameters,and laboratory indicators were collected and compared between the two groups.Multivariate logistic regression analysis was used to identify independent risk factors for microvascular complications,and a nomogram prediction model was constructed.The model's discriminative performance was assessed using receiver operating characteristic(ROC)curves,and its calibration was evaluated using calibration curves and the Hosmer-Lemeshow test.Decision curve analysis(DCA)was also performed to assess the model's clinical utility.Results Compared with the late-onset group,patients in the early-onset group exhibited more pronounced metabolic abnormalities,including higher body mass index(BMI),proportion of family history of diabetes mellitus,glycated hemoglobin(HbA1c)levels,total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),triglyceride-glucose index(TyG),and lactate dehydrogenase(LDH)levels(all P<0.05),along with a shorter disease duration and lower levels of high-density lipoprotein cholesterol(HDL-C)(P<0.05).According to a multivariate analysis,systolic blood pressure(SBP),total bilirubin(TBIL),HDL-C,LDL-C,TyG,and LDH were identified as independent risk factors for microvascular complications in patients with early-onset T2DM.A predictive model based on these factors was established as the follows,Log(P)=-19.915+0.017×SBP-0.136×TBIL-1.241×HDL-C+0.684×LDL-C+0.769×TyG+0.050×LDH.The area under the ROC curve(AUC)was 0.864(95%CI,0.820-0.907),and the Hosmer-Lemeshow test indicated good model fit(χ2=10.286,P=0.246).The slope of the DCA curve was also close to 1.Conclusion The nomogram prediction model based on SBP,TBIL,HDL-C,LDL-C,TyG,and LDH demonstrates good predictive performance for microvascular complications and can provide a reference for clinical risk stratification and individualized intervention.

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.

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.

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.

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.

Objective To summarize the clinical characteristics of primary pigmented nodular adrenocortical disease(PPNAD)and provide a reference for its clinical diagnosis and treatment.Methods A retrospective analysis was conducted on the clinical characteristics,laboratory tests,imaging examinations,treatment plans,and follow-up data of 10 PPNAD patients diagnosed and treated at the First Medical Center of Chinese PLA General Hospital from January 2008 to October 2024.Databases including CNKI,Wanfang Data Knowledge Service Platform,and PubMed were searched,and the clinical characteristics of 120 PPNAD patients reported in the literature were summarized in combination with literature reviews.Results The age at diagnosis of the 10 PPNAD patients ranged from 15 to 55 years,with a median age of onset of 21.5 years.Seven patients had the protein kinase A regulatory subunit 1 alpha(PRKAR1A)gene mutations,meeting the diagnosis criteria for Carney syndrome.One patient presented with hypertension only,while the remaining 9 patients showed typical Cushing's syndrome manifestations such as thin skin and moon face,among whom 5 experienced stagnation of height growth.In 7 patients,the adrenocorticotropic hormone(ACTH)levels were<2.2 pmol/L,with the disrupted circadian rhythm of cortisol,and the cortisol levels at midnight ranged from 243.24 to 679.83 pmol/L.None of the patients showed suppression in the low-dose dexamethasone suppression test,and 8 patients had an increase in urinary free cortisol(UFC)after dexamethasone suppression.Adrenal CT showed that 9 patients presented with unilateral adrenal nodules accompanied by contralateral thickening or bilateral adrenal nodular thickening.All 10 patients underwent initial unilateral adrenalectomy,and during follow-up,4 patients experienced symptom recurrence and underwent contralateral adrenalectomy.Most of the 120 patients reported domestically and internationally showed typical Cushing's syndrome manifestations.Surgical resection of the adrenal gland was the main treatment modality.Gene mutations were predominantly in PRKAR1A,with a few in PDE11A and PRKACA.Conclusions PPNAD is more likely to occur in adolescents.Patients with typical Cushing's syndrome manifestations should undergo screening.Imaging manifestations are atypical,and a definitive diagnosis depends on pathological and genetic diagnoses.Bilateral adrenalectomy combined with long-term postoperative hormone replacement therapy is the standard treatment protocol.Patients who undergo early unilateral adrenalectomy require long-term follow-up,with contralateral adrenalectomy performed when necessary.

Objective:To investigate the morbidity of cerebrovascular disease among residents ≥30 years in Pengzhou, Sichuan Province, and analyze the effect of physical activity level on the risk of morbidity of cerebrovascular disease.Methods:From 2004 to 2008, people from Pengzhou, Sichuan Province were randomly selected. All the local people aged 30-79 were asked to receive a questionnaire survey, physical examination, and long-term follow-up to determine the morbidity of cerebrovascular disease. The physical activity level and the morbidity of cerebrovascular disease were described, and Cox proportional hazard regression models were used to evaluate the association of domain-specific physical activity with the risk of morbidity of cerebrovascular disease.Results:In 55 126 participants, there were 5 290 new cases of cerebrovascular disease, with a cumulative incidence of 9.60%. After the adjustment for multiple confounding factors, multivariate Cox proportional hazard regression analysis showed that increased levels of occupational, transportation, and total physical activity reduced the risk of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). The highest group of occupational physical activity level had the lowest risk of cerebrovascular disease, with a hazard ratio ( HR) value of 0.81 (95% CI: 0.75-0.88), the highest group of transportation physical activity level had the lowest risk of cerebrovascular disease, with an HR value of 0.84 (95% CI: 0.78-0.91), the highest group of total physical activity level had the lowest risk of cerebrovascular disease, with an HR value of 0.87 (95% CI: 0.80-0.94), compared with the lowest group of corresponding physical activity. No association was found between the household/leisure-time physical activity level and the risk of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). Conclusions:In project areas of Pengzhou, Sichuan Province, increased physical activity has been associated with reduced morbidity of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). Increased levels of physical activity in adults are encouraged for health benefits.

Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.

Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.