AIM To investigate the in vivo pharmacokinetics of chlorogenic acid,isoquercetin,ferulic acid,isorhamnetin and shionone in Asteris Radix et Rhizoma in rats.METHODS Twelve rats were randomly assigned into 2 groups and given intragastric administration of conventional dose(0.63 g/kg)and large dose(3.3 g/kg)of Asteris Radix et Rhizoma extracts,respectively,after which blood collection was made at 0.083,0.167,0.33,0.5,0.75,1,1.5,2,4,6,8,12,24 h,UPLC-MS/MS was adopted in the plasma concentration determination of various effective constituents,and main pharmacokinetic parameters were calculated.RESULTS Various effective constituents in the large dose group demonstrated prolonged t1/2,MRT0-∞ as compared with those in the conventional dose group(P＜0.05).After dose correction,Cmax of chlorogenic acid,isoquercetin,shionone in the large dose group displayed no obvious changes(P＞0.05),while Cmax of ferulic acid,isorhamnetin,and AUC0-t,AUC0-∞ of various effective constituents were higher than those in the conventional dose group(P＜0.05).CONCLUSION Various effective constituents in the high dose of Asteris Radix et Rhizoma can maintain high-concentration and long-time effects on rat bladder tissue.

Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.

Objective:To explore the influencing factors of post-percutaneous coronary intervention(PCI)positivity in young and middle-aged patients with acute myocardial infarction(AMI)and simultaneously assess its mediating effect in the relationship between illness-related shame and psychosocial adjustment.Methods:A total of 178 patients,who admit-ted in Cangzhou People's Hospital between October 2021 and December 2022 for AMI,underwent PCI,and were subse-quently defined as frailty after PCI,were selected.General demographic information survey forms,Patient Activation Measure(PAM),Social Impact Scale(SIS),and Psychosocial Adjustment to Illness Scale Self-Report(PAIS-SR)were applied to investigate the patients.Clinical data characteristics of the patients were analyzed.Pearson correlation analysis was conducted to investigate the association among PAM score,SIS score and PAIS-SR score.Multivariate linear stepwise regression analysis was employed to identify the influencing factors of positivity.The Bootstrap procedure in the Process plugin was used to validate the mediating effect of positivity between illness-related shame and psychosocial adjustment.Results:In this study,PAM score was(57.87±7.02)points,SIS score was(52.07±12.66)points,and PAIS-SR score was(61.07±10.58)points.Pearson correlation analysis indicated that PAM score was significant negatively correlated with SIS score and PAIS-SR score(r=-0.439,-0.504,P＜0.001 all),and SIS score was significant positively corre-lated with PAIS-SR score(r=0.722,P＜0.001).Multivariate linear stepwise regression analysis indicated that male(B=2.226,P=0.020),educational level(B=2.194,P=0.005)and stigma associated with illness(B=-0.210,P＜0.001)can influence the postoperative positivity of patients.Mediation effect analysis indicated that illness-related shame had a direct effect on psychosocial adjustment,accounting for 85.92％of the total effect,while positivity partially media-ted the relationship between illness-related shame and psychosocial adjustment with an effect size of 14.08％.Conclusion:Illness-related shame not only directly affects the psychosocial adjustment in frailty AMI patients after PCI,but also exerts an indirect influence on it through positivity.Medical staff should implement targeted strategies to enhance patients'positiv-ity,thereby reducing the negative impact of illness-related shame on psychosocial adjustment.

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.

Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.

Objective:To explore the influencing factors of post-percutaneous coronary intervention(PCI)positivity in young and middle-aged patients with acute myocardial infarction(AMI)and simultaneously assess its mediating effect in the relationship between illness-related shame and psychosocial adjustment.Methods:A total of 178 patients,who admit-ted in Cangzhou People's Hospital between October 2021 and December 2022 for AMI,underwent PCI,and were subse-quently defined as frailty after PCI,were selected.General demographic information survey forms,Patient Activation Measure(PAM),Social Impact Scale(SIS),and Psychosocial Adjustment to Illness Scale Self-Report(PAIS-SR)were applied to investigate the patients.Clinical data characteristics of the patients were analyzed.Pearson correlation analysis was conducted to investigate the association among PAM score,SIS score and PAIS-SR score.Multivariate linear stepwise regression analysis was employed to identify the influencing factors of positivity.The Bootstrap procedure in the Process plugin was used to validate the mediating effect of positivity between illness-related shame and psychosocial adjustment.Results:In this study,PAM score was(57.87±7.02)points,SIS score was(52.07±12.66)points,and PAIS-SR score was(61.07±10.58)points.Pearson correlation analysis indicated that PAM score was significant negatively correlated with SIS score and PAIS-SR score(r=-0.439,-0.504,P＜0.001 all),and SIS score was significant positively corre-lated with PAIS-SR score(r=0.722,P＜0.001).Multivariate linear stepwise regression analysis indicated that male(B=2.226,P=0.020),educational level(B=2.194,P=0.005)and stigma associated with illness(B=-0.210,P＜0.001)can influence the postoperative positivity of patients.Mediation effect analysis indicated that illness-related shame had a direct effect on psychosocial adjustment,accounting for 85.92％of the total effect,while positivity partially media-ted the relationship between illness-related shame and psychosocial adjustment with an effect size of 14.08％.Conclusion:Illness-related shame not only directly affects the psychosocial adjustment in frailty AMI patients after PCI,but also exerts an indirect influence on it through positivity.Medical staff should implement targeted strategies to enhance patients'positiv-ity,thereby reducing the negative impact of illness-related shame on psychosocial adjustment.

The incidence rate of kidney diseases in China has always remained high.At present,the clinical treat-ment mainly focuses on symptomatic treatment to delay the progression of the disease,and there is a lack of eco-nomical and effective treatment methods.MicroRNA plays an important regulatory role in the occurrence and devel-opment of diseases.This study aims to explore the role and regulatory mechanism of miR-142a-3p in adriamycin(ADR)-induced renal tubular epithelial cell(TCMK-1)injury,with a focus on its potential as a therapeutic target for ADR nephropathy.First,cell viability was assessed using the CCK-8 kit,and a mouse renal tubular epithelial cell model induced by ADR was established.Subsequently,alterations in miR-142a-3p and its target gene ATG16L1 mRNA levels were quantified using RT-qPCR.Western blotting was used to detect the protein levels of autophagy marker proteins and pyroptosis marker proteins.Monodansylcadaverin(MDC)staining was performed and the autophagy of cells was detected by flow cytometry.The results showed that the relative expression of miR-142a-3p in TCMK-1 cells induced by ADR was increased and the relative expression of its target gene ATG16L1 was decreased(P＜0.0001).Western blotting results showed that the levels of p62(P＜0.001)and pyroptosis-related proteins(P＜0.001)were increased,while the protein levels of autophagy-related proteins were decreased(P＜0.05).The flow cytometry results showed that there was no difference in the mean fluorescence intensity of autoph-agosomes between the ADR group and the autophagosome inhibitor group(3-MA group)(P＞0.05),indicating that after ADR induction,cell autophagy was inhibited and pyroptosis was enhanced.When the expression of miR-142a-3p was inhibited by transfecting miR-142a-3p inhibitor,the relative expression level of the target gene ATG16L1 was restored(P＜0.001).Western blotting showed that the protein level of p62(P＜0.01)and pyropto-sis-related proteins(P＜0.01)were decreased,and the protein level of autophagy-related proteins was restored(P＜0.001).Flow cytometry results further indicated that cell autophagy was restored(P＜0.0001).In conclusion,ADR targets A TG1 6L1 through miR-142a-3p to reduce the autophagy level of TCMK-1,and simultaneously activates GSDMD-mediated pyroptosis.