Objective:To investigate the genetic mutation characteristics of patients with bilateral macronodular adrenocortical disease（BmacAD）and to analyze the clinical phenotypes and adrenal nodule transcriptomic profiles associated with different genotypes.Methods:This retrospective study analyzed the clinical data of 37 patients diagnosed with BmacAD by clinical and pathological assessment who underwent surgery at Peking Union Medical College Hospital from January 2001 to December 2024. Data included symptoms and signs related to hypercortisolism，24-hour urinary free cortisol，plasma adrenocorticotropic hormone（ACTH），and overnight low-dose dexamethasone suppression test results. Whole-exome sequencing（WES）was performed on frozen adrenal hyperplasia tissue samples from surgical specimens and matched frozen residual blood samples for all patients to screen for germline and somatic mutations. Sanger sequencing was used to validate some of the identified mutations. The relation between genetic mutations and clinical features was analyzed. Transcriptome sequencing of the hyperplastic tissues was conducted，and unsupervised clustering，differential gene expression analysis，and pathway enrichment analysis were used to compare the transcriptomic profiles of patients with different genotypes.Results:A total of 37 cases were included（23 males and 14 females），aged between 31?68 years old. Among the patients with available clinical data，most exhibited signs of hypercortisolism，including hypertension（100.0%，36/36），diabetes（50.0%，18/36），and centripetal obesity（55.9%，19/34），accompanied by relevant endocrine abnormalities such as elevated 24-hour urinary free cortisol（79.4%，27/34），suppressed ACTH（77.8%，28/36），and a positive overnight low-dose dexamethasone suppression test（45.2%，14/31）. WES and Sanger sequencing revealed that ARMC5 gene mutations were the most common. Among the 37 patients，33（89.2%）had ARMC5 germline mutations，and 31（83.8%）concurrently harbored ARMC5 somatic mutations，including 3 cases of loss of heterozygosity. Two patients without detectable ARMC5 mutations both carried a somatic p.S45P mutation in the CTNNB1 gene and neither had typical manifestations of hypercortisolism. Transcriptome sequencing results suggested that patients with ARMC5 mutations had an upregulation of pathways related to steroid secretion.Conclusions:The majority of BmacAD patients present with typical manifestations of hypercortisolism，while a minority exhibit only mild autonomous cortisol secretion without obvious symptoms. Biallelic inactivation of the ARMC5 gene is the primary genetic driver of this disease，leading to more severe hypercortisolism by upregulating steroid hormone secretion. CTNNB1 mutations may be involved in the pathogenesis of some patients without ARMC5 mutations.

Objective:To explore the value of metanephrine, normetanephrine, and some steroid hormones in the assessment of adrenal venous sampling (AVS).Methods:This retrospective study enrolled 101 patients with primary aldosteronism who underwent AVS at Peking Union Medical College Hospital between June 1, 2021, and October 1, 2024. Multiple hormones, including aldosterone, cortisol, metanephrine, normetanephrine and steroid hormone profiles, were measured in samples from the inferior vena cava and bilateral adrenal veins during AVS. Selectivity index and lateralization index were calculated based on the levels of different hormones to determine successful AVS cannulation (selectivity index≥2) and aldosterone hypersecretion lateralization (lateralization index≥2). Patients who underwent unilateral adrenalectomy were followed for at least 6 months. Clinical and biochemical outcomes were assessed according to the Primary Aldosteronism Surgical Outcome (PASO) criteria, with biochemical remission defined as achieving complete or partial biochemical remission postoperatively. The efficacy of different hormones relative to cortisol for calculating selectivity index and lateralization index was evaluated for subtype classification.Results:The age at diagnosis of the enrolled patients was (50.5±9.6) years, including 77 males. Regarding the selectivity index, five hormones including metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone demonstrated significantly higher selectivity index compared to cortisol (all P<0.05). Based on the cortisol-derived selectivity index, AVS cannulation was unsuccessful in 8 patients; using the five indices, unsuccessful cannulation occurred in 2, 2, 3, 4, and 5 patients, respectively. Based on postoperative follow-up, 55 patients were identified as having unilateral surgically relievable primary aldosteronism. In identifying these patients, the performance of metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone was non-inferior to cortisol, correctly identifying 95% (52/55), 93% (51/55), 91% (50/55), 87% (48/55), and 89% (49/55) of cases, respectively. However, among these patients, there were no statistically significant differences in the success rate of intubation in AVS and the ability to identify patients with unilateral primary aldosteronism between the five indicators and cortisol (all P>0.05). Using cortisol-based lateralization as the reference standard, androstenedione and dehydroepiandrosterone both achieved an accuracy of 90% (84/93) for determining the lateralized side, while 17α-hydroxypregnenolone, normetanephrine, and metanephrine achieved accuracies of 89% (83/93), 81% (74/93), and 80% (73/93), respectively. Conclusion:Metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone and dehydroepiandrosterone could increase the success rate of intubation in AVS, with a high ability to identify patients with unilateral primary aldosteronism, and are expected to replace cortisol as new indicators of AVS.

Objective:To investigate the genetic mutation characteristics of patients with bilateral macronodular adrenocortical disease（BmacAD）and to analyze the clinical phenotypes and adrenal nodule transcriptomic profiles associated with different genotypes.Methods:This retrospective study analyzed the clinical data of 37 patients diagnosed with BmacAD by clinical and pathological assessment who underwent surgery at Peking Union Medical College Hospital from January 2001 to December 2024. Data included symptoms and signs related to hypercortisolism，24-hour urinary free cortisol，plasma adrenocorticotropic hormone（ACTH），and overnight low-dose dexamethasone suppression test results. Whole-exome sequencing（WES）was performed on frozen adrenal hyperplasia tissue samples from surgical specimens and matched frozen residual blood samples for all patients to screen for germline and somatic mutations. Sanger sequencing was used to validate some of the identified mutations. The relation between genetic mutations and clinical features was analyzed. Transcriptome sequencing of the hyperplastic tissues was conducted，and unsupervised clustering，differential gene expression analysis，and pathway enrichment analysis were used to compare the transcriptomic profiles of patients with different genotypes.Results:A total of 37 cases were included（23 males and 14 females），aged between 31?68 years old. Among the patients with available clinical data，most exhibited signs of hypercortisolism，including hypertension（100.0%，36/36），diabetes（50.0%，18/36），and centripetal obesity（55.9%，19/34），accompanied by relevant endocrine abnormalities such as elevated 24-hour urinary free cortisol（79.4%，27/34），suppressed ACTH（77.8%，28/36），and a positive overnight low-dose dexamethasone suppression test（45.2%，14/31）. WES and Sanger sequencing revealed that ARMC5 gene mutations were the most common. Among the 37 patients，33（89.2%）had ARMC5 germline mutations，and 31（83.8%）concurrently harbored ARMC5 somatic mutations，including 3 cases of loss of heterozygosity. Two patients without detectable ARMC5 mutations both carried a somatic p.S45P mutation in the CTNNB1 gene and neither had typical manifestations of hypercortisolism. Transcriptome sequencing results suggested that patients with ARMC5 mutations had an upregulation of pathways related to steroid secretion.Conclusions:The majority of BmacAD patients present with typical manifestations of hypercortisolism，while a minority exhibit only mild autonomous cortisol secretion without obvious symptoms. Biallelic inactivation of the ARMC5 gene is the primary genetic driver of this disease，leading to more severe hypercortisolism by upregulating steroid hormone secretion. CTNNB1 mutations may be involved in the pathogenesis of some patients without ARMC5 mutations.

Objective:To explore the value of metanephrine, normetanephrine, and some steroid hormones in the assessment of adrenal venous sampling (AVS).Methods:This retrospective study enrolled 101 patients with primary aldosteronism who underwent AVS at Peking Union Medical College Hospital between June 1, 2021, and October 1, 2024. Multiple hormones, including aldosterone, cortisol, metanephrine, normetanephrine and steroid hormone profiles, were measured in samples from the inferior vena cava and bilateral adrenal veins during AVS. Selectivity index and lateralization index were calculated based on the levels of different hormones to determine successful AVS cannulation (selectivity index≥2) and aldosterone hypersecretion lateralization (lateralization index≥2). Patients who underwent unilateral adrenalectomy were followed for at least 6 months. Clinical and biochemical outcomes were assessed according to the Primary Aldosteronism Surgical Outcome (PASO) criteria, with biochemical remission defined as achieving complete or partial biochemical remission postoperatively. The efficacy of different hormones relative to cortisol for calculating selectivity index and lateralization index was evaluated for subtype classification.Results:The age at diagnosis of the enrolled patients was (50.5±9.6) years, including 77 males. Regarding the selectivity index, five hormones including metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone demonstrated significantly higher selectivity index compared to cortisol (all P<0.05). Based on the cortisol-derived selectivity index, AVS cannulation was unsuccessful in 8 patients; using the five indices, unsuccessful cannulation occurred in 2, 2, 3, 4, and 5 patients, respectively. Based on postoperative follow-up, 55 patients were identified as having unilateral surgically relievable primary aldosteronism. In identifying these patients, the performance of metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone was non-inferior to cortisol, correctly identifying 95% (52/55), 93% (51/55), 91% (50/55), 87% (48/55), and 89% (49/55) of cases, respectively. However, among these patients, there were no statistically significant differences in the success rate of intubation in AVS and the ability to identify patients with unilateral primary aldosteronism between the five indicators and cortisol (all P>0.05). Using cortisol-based lateralization as the reference standard, androstenedione and dehydroepiandrosterone both achieved an accuracy of 90% (84/93) for determining the lateralized side, while 17α-hydroxypregnenolone, normetanephrine, and metanephrine achieved accuracies of 89% (83/93), 81% (74/93), and 80% (73/93), respectively. Conclusion:Metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone and dehydroepiandrosterone could increase the success rate of intubation in AVS, with a high ability to identify patients with unilateral primary aldosteronism, and are expected to replace cortisol as new indicators of AVS.

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Myelodysplastic syndrome(MDS)is a malignant clonal disease with high heterogeneity in cytogenetics and molecular genetics,and the risk of progression to acute myeloid leukemia(AML)is extremely high.Transforming growth factor-β(TGF-β)is closely related to the pathogenesis of MDS.It is a key executor of immune homeostasis and immune tolerance,and can inhibit the expansion and function of many components of immune system.TGF-β signaling pathway can regulate hematopoietic cells and immune cells in microenvironment,inhibit their normal biological functions,and thus accelerate the progression of MDS.This study reviews regulatory effects of TGF-β signaling pathway on MDS blood cells,T lymphocytes,natural killer cells and macrophages in recent years,and provides a new perspective for the pathogenesis and treatment of MDS.

Objective:To investigate the clinical features and long-term prognosis of patients co-existing with ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE).Methods:Totally 358 OMA patients were retrospectively analyzed, who had a minimum of 8 years follow-up after laparoscopic cystectomy, which was performed by one professional endometriosis surgery team at Peking Union Medical College Hospital from January 2009 to April 2013. All women were divided into DIE group and non-DIE group, and analysis was performed in preoperative characteristics, surgical findings and postoperative outcomes during follow-up.Results:A total of 358 OMA patients were included, of which 190 patients (53.1%, 190/358) were in the DIE group, while other 168 patients (46.9%, 168/358) in the non-DIE group. The average ages between the two groups were (33.7±5.4), (32.5±5.3) years ( P=0.047), the average parity was (0.4±0.6) times vs (0.3±0.5) times ( P=0.079). There were significant differences in the proportions of moderate to severe dysmenorrhea [67.4% (128/190) vs 56.5% (95/168)], chronic pelvic pain [24.2% (46/190) vs 7.7% (13/168)], and the increase in CA 125 [79.9% (139/190) vs 65.2% (101/168)] between the two groups (all P<0.05). The average operation time in the DIE and non-DIE groups was (75±21) vs (39±36) minutes ( P<0.01). There was a significant difference in adenomyosis presence between the two groups [41.6% (79/190) vs 22.0% (37/168); P=0.001]. All patients were followed up for at least 8 years. At the end of the follow-up, though the DIE group was with higher total rate of disease relapse, yet no significant difference was found between the two groups in statistical comparison [21.6% (41/190) vs 16.1% (27/168); P=0.185]. A total of 41 cases in the DIE group recurred, the recurrence rate of pain was 15.8% (30/190), and the recurrence rate of cyst was 8.4% (16/190); 27 cases had recurrence after operation in the non-DIE group, the recurrence rate of pain was 8.9% (15/168), and the recurrence rate of cyst was 10.7% (18/168). There were no significant differences in the pain recurrence rate ( P=0.067) and cyst recurrence rate ( P=0.460) between the two groups. As for the successfully pregnant patients, live birth rates were 100.0% (65/65) vs 94.4% (68/72) between DIE group and non-DIE groups ( P=0.120). Conclusions:Compared with the non-DIE group, OMA patients with concurrent DIE might have severe pain symptoms, higher probability of abnormal CA 125 levels and more severe pelvic adhesions. Although there are no significant differences in the total recurrence rate and the recurrence rate of various types between the two groups, the proportion of pain recurrence in the DIE group is higher than that in the non-DIE group. In terms of fertility outcomes, patients in the DIE group are with lower likelihood of pregnancy after surgery during the long-time follow-up. DIE has no significant influence on the fertility outcome.

Skull deformity is common ailment of infants,and maybe cause developmental deformity,with high incidence in China.In this article,we reviewed the related factors,prevention and treatment for skull deformity,aimed at providing references for its further application.

Objective: To review and discuss the experience of diagnosis and treatment of adrenal ganglioneuroma. Methods: Clinical data of 80 cases of adrenal ganglioneuroma undergoing surgery during January 1982 to May 2017 at Peking Union Medical College Hospital were retrospectively analyzed. There were 36 male and 44 female patients. Age ranged from 8 to 69 years old (mean 37.7 years old). The tumor diameter were 1.5 to 18.0 cm (mean 4.3 cm). There were 61 cases of adrenal ganglioneuroma diagnosed by imaging examination. All patients underwent adrenalectomy. Results: All procedures were performed successfully without serious complication. Including 15 open surgery and 64 retroperitoneal laparoscopic surgery. One laparoscopic case conversion to open surgery. The pathological diagnosis was adrenal ganglioneuroma. Fifteen cases were mixed with other tumor components. No recurrence or metastasis was observed during the follow-up of 2 months to 35 years. Conclusions The diagnostic techniques for adrenal ganglioneuroma are helpful to judge the tumor property before operation. The laparoscopic surgery has become the current method for resecting tumors. It shows advantages of small trauma and speedy recovery. The relationship between tumor and surrounding tissues should be understand clearly before operation. Full preparation must be made before operation if adrenal ganglioneuroma mixed with other tumor components.

Objective: To investigate the impact factors for central neck lymph node metastases(CLNM) of papillary thyroid carcinoma(PTC). Methods: A total of 498 patients with PTC who underwent total or hemi-thyroidectomy plus central neck lymph node dissection between January 2014 and July 2016 were included. Univariate and multivariate analyses were performed to identify clinicopathological characteristics, thyroid function parameters and US findings that associated with CLNM of PTC. A nomogram was developed to predict the probability of CLNM. The receiver operating characteristic curve(ROC) was used to estimate the efficiency of the nomogram. Results: Among 498 patients, 284 patients were affected by CNLM. The sensitivity and specificity of US in predicting PTC metastasis in the central neck were 31.3% and 88.3%, respectively. Univariate and multivariate analyses showed that gender, age, number and size of suspicious malignant nodules in thyroid, and suspicious lymph node metastasis detected by ultrasonography were independently correlated with CLNM. The ROC showed that the AUC was 0.748, with sensitivity of 80.8%, and specificity of 59.8%. Conclusions Gender, age, number and size of suspicious malignant nodules in thyroid, suspicious lymph node metastasis were predictive factors for CLNM in patients with PTC. The nomogram developed based on related factors with CLNM is more sensitive than sonographic central neck lymph node features in predicting the probability of CLNM.