Objective:To explore the causal association between insulin-like growth factor-1(IGF-1)and colorectal cancer(CRC)based on two sample Mendelian randomization(MR)analysis.Methods:A bidirectional two sample MR analysis was conducted based on publicly aggregated data from the IEU OpenGWAS project.The inverse variance weighted(IVW)method was used as the main analysis model to assess the causal relationship between IGF-1 and CRC.Additional analyses were performed using weighted median(WM),MR-Egger regression,weighted mode estimator(WME),and simple mode(SM)methods.Sensitivity analysis was performed to assess the robustness of the results.Results:A total of 386 single nucleotide polymorphisms(SNPs)were selected as instrumental variables(IVs)with IGF-1 as the exposure factor.The MR analysis results revealed a positive causal association between IGF-1 and the risk of CRC[odds ratio(OR)=1.178,95％confidence interval(CI):1.092-1.272)](P＜0.001),and the association remained significant after adjusting for height[OR(95％CI)=1.214(1.111,1.327)](P＜0.001).Cochran's Q-test showed heterogeneity among the IVs(P＜0.05),while the horizontal pleiotropy of IV was not detected by the MR-Egger regression(P＞0.05).The leave-one-out analysis showed that the MR results were robust.Reverse MR analysis indicated no reverse causal relationship between IGF-1 and CRC[OR(95％CI):1.017(0.997,1.037)](P=0.103).Conclusion:There is a causal relationship between IGF-1 level and CRC,and elevated IGF-1 level could be a risk factor for CRC.

Objective:To evaluate the function of serum dehydroepiandrosterone sulfate (DHEAS) in adult adrenal space-occupying lesions.Methods:In this cross-sectional study, 395 patients with adrenal space-occupying lesions who had their DHEAS levels measured were collected from the First Medical Center of Chinese PLA General Hospital from January 2010 to June 2021. They were divided into the adrenal Cushing syndrome (ACS) group ( n=100) and non-ACS group ( n=295). The former was divided into the cortisol-producing adrenal adenoma (CPA) group ( n=67) and primary bilateral macronodular adrenal hyperplasia (PBMAH) group ( n=33). Clinical data of each group were collected and compared among groups by independent samples t-test, chi-square test, and Mann-Whitney U test. Serum DHEAS ratio corrected for age and sex was further constructed to identify the receiver operating characteristic curve and the optimal tangent point value for different adrenal occupation. Results:Patients in the ACS group were younger (44.9±13.7 vs. 49.9±12.5, P=0.001); had a larger proportion of women (79/100 vs.139/295, P=0.001); and had higher cortisol levels [8∶00Am, 497.31 (343.52, 606.50) vs. 353.11 (267.50, 487.91) nmol/L, P<0.001] than those in the non-ACS group. The serum DHEAS level and ratio in the ACS group were significantly lower than those in the non-ACS group [0.50 (0.40, 1.21) vs. 2.68 (1.56, 4.32) &mu;mol/L, 1.00 (0.43, 1.68) vs. 3.17 (2.21, 4.54), both P<0.001]. When the serum DHEAS ratio cut-off point was 1.29, the sensitivity and specificity for differential diagnosis of ACS and non-ACS were 72.0% and 91.5% respectively. The ratio of DHEAS in the CPA group was lower [0.58 (0.27, 1.05) vs. 1.14 (1.04, 2.40), P<0.001] than that in the PBMAH group. When the serum DHEAS ratio cut-off point was 0.99, the sensitivity and specificity for differential diagnosis of CPA and PBMAH were 64.2% and 81.2% respectively. Conclusion:Corrected age-sex DHEAS ratio can assist in the functional assessment of adrenal space-occupying lesions.

Objective:The study retrospectively analyzed the etiology, clinical manifestations, emergency treatment and etiological treatment of a large sample of cases with hypercalcemic crisis.Methods:The clincial data of patients with hypercalcaemia cirisis who were administered in First Medical Center of Chinese PLA General Hospital from January 2009 to July 2022 were analyzed, inculding the general data, clinical manifestations, etiology, photographic examination, emergency treatment, etiological treatment, serological examination before and after treatment, pathological immunohistochemical findings and prognosis.Results:A total of 143 hypercalcaemia crisis patients(84 males and 59 females) with a mean age of 53.51±16.60 were enrolled. The most common disease was hyperparathyroidism(62/143), followed by solid malignancy(57/143) and multiple myeloma(12/143). Patients presented with digestive system symptoms at 76.91%, followed by neurological symptoms at 63.60%, urinary system symptoms at 58.76%, musculoskeletal symptoms at 55.23%, and cardiovascular system symptoms at 32.91%. After emergency calcium-lowering treatment, the remission rate of hypercalcemic crisis in 143 patients was 100%(143/143), and after etiological treatment, the remission rate of hypercalcemia was 85.31%(122/143).Conclusion:Early identification, emergency treatment and etiology treatment of hypercalcaemia crisis are essential. Effective treament with comprehensive calcium reduction can quickly relieve clinical symptoms and create opportunities for treatment for the cause. Targeted etiological interventions can lead to the correction or long-term remission of hypercalcemia.

Objective To compare the diagnostic value of adrenocorticotropic hormone(ACTH)stimulation test(AST)with different doses of ACTH combined with midnight administration of 1 mg dexamethasone for the determination of the subtypes of primary hyperaldosteronism(PA).Methods This is a prospective observational study.Patients diagnosed with PA in the Department of Endocrinology,the First Medical Center of of Chinese PLA General Hospital from January 1,2020 to September 30,2022 underwent AST with different doses of ACTH.All patients received 1 mg dexamethasone at midnight for inhibition.Then,the patients were randomly assigned to 25-unit and 50-unit ACTH treatment groups by a ratio of 1:2.Subtype classification and diagnosis of aldosterone-producing adenoma(APA)and idiopathic hyperaldosteronism(IHA)was made on the basis of adrenal venous blood samples and/or postoperative pathology and clinical follow-up findings.Receiver operating characteristics(ROC)curves were plotted to examine the diagnostic efficacy and the difference of AST by varying doses of ACTH in distinguishing APA and IHA.Results A total of 82 patients,including 49 patients with APA(59.8%)and 33 patients with IHA(40.2%),were enrolled.There were 29 patients in the 25-unit ACTH group(35.4%)and 53 patients in the 50-unit ACTH group(64.6%).There were no significant differences in age,sex,blood pressure,minimum serum potassium,and biochemical parameters between the 25-unit and 50-unit groups.After ACTH stimulation,plasma aldosterone concentration(PAC),cortisol(F),and PAC/F at different points of time showed no statistical difference between the two groups(P>0.05).The area under the curve(AUC)of PAC in the 25-unit group was higher than that of PAC/F.The AUC of PAC reached the maximum at 90 minutes(0.948,95%confidence interval[CI]:0870-1.000)and the optimal cutoff was 38.0 ng/dL,which had a sensitivity of 92.9%and a specificity of 86.7%for differentiating APA and IHA.Similar to the 25-unit group,the maximum AUC of PAC in the 50-unit group was greater than that of PAC/F.The AUC of PAC reached the maximum 90 minutes(0.930,95%CI:0.840-0.994)and the optimal cutoff was 39.6 ng/dL,which had a sensitivity of 91.2%and a specificity of 83.3%.The AUC of PAC at different points of time in the 25-unit ACTH group(0.862-0.948)was greater than that of 50-unit ACTH group(0.823-0.930),but the difference was not statistical significance.Conclusion AST with 25-unit or 50-unit ACTH combined with small-dose dexamethasone can be used in PA subtype determination,ie,differentiation between APA and IHA.The optimal PAC cut-off values for 25-unit or 50-unit ACTH are similar,being 38.0 ng/dL and 39.6 ng/dL,respectively,and both cutoff values show higher sensitivity and specificity at 90 min.The AST with 25-unit ACTH has the smaller dose and the better safety.Therefore,it is recommended for the diagnosis of PA subtypes.

Objective:To explore the characteristics of the association between the triglyceride glucose (TyG) index and nonfatal cardio-cerebrovascular disease risk in a community population.Method:This was a prospective cohort study. From December 2011 to April 2012, the first investigation was conducted among subjects with more than 40-year old who were from Shijingshan district and Pingguoyuan community in Beijing. The second investigation was conducted from April to October 2015. All the subjects were divided into three groups according to the tertile of the TyG index at baseline. The multivariate Cox proportional risk regression model was established to explore the correlation between the TyG index and nonfatal cardio-cerebrovascular disease risk and the Kaplan-Meier survival curve of the TyG index group was drawn. Subgroup analyses were performed according to age, gender, body mass index, type 2 diabetes mellitus (T2DM), hypertension, and hyperlipidemia to determine the correlation characteristics between the TyG index and nonfatal cardio-cerebrovascular disease among subgroups.Results:A total of 9 577 subjects were finally included to analyze. The mean follow-up time of this study was (34.14±3.84) months. During the follow-up, 363 subjects (3.8%) occurred nonfatal cardio-cerebrovascular disease. The multivariate Cox regression analysis results showed that the hazard ratio ( HR) of nonfatal cardio-cerebrovascular disease in the high TyG index group was 1.54 (95% CI 1.19-1.98), 1.60 (95% CI 1.23-2.10), and 1.57 (95% CI 1.20-2.05) in the three models, compared with the low TyG index group. The Kaplan-Meier analysis showed that the risk of nonfatal cardio-cerebrovascular disease increased from the low-TyG index group to the high-TyG index group ( P=0.015). In the six subgroups analysis, only gender was shown to have a significant interaction effect with the TyG index and nonfatal cardio-cerebrovascular disease risk. In the female population, the risk of nonfatal cardio-cerebrovascular disease is significantly increased with the increase in the TyG index level ( P<0.001). Conclusions:A high TyG index is independently related to the increased risk of nonfatal cardio-cerebrovascular disease in the Beijing community population. Gender has a significant interaction with the TyG index and nonfatal cardio-cerebrovascular disease risk. Therefore, the TyG index may be a useful marker to predict the nonfatal cardio-cerebrovascular disease risk of a community population.

Background/Aims: The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation. Methods: We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals. Results: A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers.The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers. Conclusions We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.

Objective:To summarize the clinical characteristics, reveal evolutionary patterns, and enhance the understanding of idiopathic isolated adrenocorticotripin(ACTH)deficiency(IIAD)by conducting a clinical analysis and follow-up.Methods:The clinical data of 12 patients with IIAD in our center were analyzed retrospectively, and the patients were further followed up to summarize the clinical characteristics of these patients.Results:Among 12 patients with IIAD, the ratio of male to female was 3∶1. The onset showed a bimodal trend, with 2 cases occurring below the age of 18(at 1 year and 11 years respectively), and 10 cases occurring in adults, with an average onset age of 59.4 years old. In adults, the main symptoms were chronic fatigue, anorexia, and weight loss, while pediatric patients exhibited hypoglycemia and seizures. Hyponatremia(50%)was a common biochemical abnormality. ACTH, cortisol, and 24 h urinary free cortisol were significantly lower in all patients, and the functions of other pituitary gland axes were normal. All patients were normal except 2 patients with pituitary MRI showing vacuolar sella turcica. The most common accompanying disease was Hashimoto thyroiditis. After glucocorticoid replacement therapy, all patients showed symptom improvement. The replacement doses include prednisone acetate at 2.5-7.5 mg/d or hydrocortisone at 12-20 mg/d. All the 8 patients were still alive with ongoing ACTH deficiency, without any decline in other pituitary axis functions or occurrence of other diseases.Conclusion:IIAD exhibits a bimodal onset pattern with a higher prevalence in males. Symptoms persist in a chronic and stable manner without remission. Prognosis is favorable with physiological dose of glucocorticoid replacement therapy.

Objective:To analyzed clinical characteristics of pituitary growth hormone(GH) adenomas patients with different responses to oral glucose inhibitory GH test.Methods:The clinical data of 50 patients with pituitary GH adenomas newly diagnosed with complete test data and case data in the Department of Endocrinology of Chinese PLA General Hospital was retrospectively analyzed from 2016 to 2021. The cases were divided into two groups according to the cutoff point of GH elevating to 50% of basaline during oral glucose test: abnormal elevation group(A group, n=16) and non-elevation group(B group, n=34). The clinical features, biochemistry, iconography, and immunohistochemistry of the two groups were analyzed. Results:The serum total cholesterol(TC)[(3.9±0.8) vs (4.6±0.9)mmol/L], 120 minutes insulin after glucose loading [11.2(4.4, 25.0) vs 92.0(10.8, 311.8)mU/L], long [1.0(0.4, 2.1) vs 1.5(0.5, 7.3) cm] and short[0.6(0.3, 1.3) vs 1.0(0.5, 5.8)cm] diameters of adenomas in A group were less than those in B group(all P<0.05) while insulin-like growth factor Ⅰ(IGF-Ⅰ) level was higher [(908.2±233.7) vs (743.1±273.1) ng/mL, P<0.05]. There were no significant differences in sex, age, disease course, clinical features, random GH, homeostasis model assessment of insulin resistance index(HOMA-IR), pituitary adenoma site, and invasive properties between the two groups. The immunohistochemical positive rates of ACTH(33% vs 0%) and prolactin(100% vs 28.6%)in A group were higher than those in B group( P<0.05). Conclusion:Pituitary GH adenomas patients with a paradoxical GH response pattern display lower serum TC and 120 minutes insulin levels as well as higher IGF-Ⅰ concentration and proportion of pituitary microadenomas. " Pure" growth hormone tumors may represent entities of a particular class of diseases in acromegaly.

Objective:To provide insight into the diagnosis for clinicians, the clinical characteristics, diagnosis and treatment history of 3 patients with 21-hydroxylase deficiency (21-OHD) and testicular adrenal rest tumors (TART) were analyzed.Methods:The clinical, laboratory and imaging data of 3 male patients with 21-OHD and TART, confirmed with CYP21 gene sequencing, from May 2010 to May 2021 in the First Medical Center of Chinese PLA General Hospital were analyzed retrospectively. The treatment strategy and clinical outcome were followed up.Results:All the 3 patients were first diagnosed with bilateral adrenal mass at the age of 27-42 years old. They were 145-162 cm tall. The levels of progesterone, 17-hydroxyprogesterone, and adrenocorticotropic hormone (ACTH) of the 3 patients were relatively high, and that of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) of the 3 patients were low. Testosterone level of 1 patient was significantly elevated, and that of the other 2 patients was below the lower limit of normal range. Testicular ultrasound showed heterogeneous hyperechoic masses in both testes. CT of the adrenal glands showed bilateral adrenal enlargement with mass. All 3 patients were treated with dexamethasone. After 4-96 months of follow-up, 17-hydroxyprogesterone level was kept above the median normal level. One of the patients got married and had a baby after treatment. The sizes of adrenal hyperplasia and testicular masses reduced to various degrees with the change of the testicular masses being proportional to that of adrenal hyperplasia.Conclusions:Patients with 21-OHD are prone to have TART, leading to the impaired testicular function. Early glucocorticold therapy is beneficial to the reduction of TART and restoration of testicular function.

Cystic lesions in the sellar region are one of the special types of space-occupying lesions in the sellar region, including cystic pituitary adenoma, craniopharyngioma, Rathke′s cyst, pituitary apoplexy, pituitary abscess, arachnoid cyst, epidermoid Cysts, etc. Each type of lesion has its corresponding treatment principles and strategies, and the prognosis also varies. Therefore, a clear preoperative diagnosis helps to hammer out the right treatment plan. If the volume of cystic lesions in the sellar region increases to a certain extent, mass effect and changes in pituitary hormones may occur. Different types of cystic lesions have their own characteristics, so as MRI and other imaging. In this paper, the diagnosis and differential diagnosis are analyzed and summarized based on clinical and imaging features, flow chart of differential diagnosis is developed.