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.

In 2022, WHO updated the classification and concept of adrenal cortical and medullary tumors. In terms of adrenal cortical tumors, the WHO classification further standardizes the nomenclature of nodular adrenal cortical disease and refines the pathological classification of primary aldosteronism. In terms of adrenal medullary tumors, the WHO classification unifies the concepts of pheochromocytoma and paraganglioma, and reclassifies various concepts, including paraganglioma-like neuroendocrine tumors. The new standards not only cover the clinical manifestations of the disease, but also include other multiple aspects such as the histological origin of the disease, immunohistochemical manifestations, physiological mechanisms of the disease, hereditary susceptibility and prognostic factors. This article intends to explore how to improve the diagnostic and therapeutic level of adrenal tumors.

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.

In 2022, WHO updated the classification and concept of adrenal cortical and medullary tumors. In terms of adrenal cortical tumors, the WHO classification further standardizes the nomenclature of nodular adrenal cortical disease and refines the pathological classification of primary aldosteronism. In terms of adrenal medullary tumors, the WHO classification unifies the concepts of pheochromocytoma and paraganglioma, and reclassifies various concepts, including paraganglioma-like neuroendocrine tumors. The new standards not only cover the clinical manifestations of the disease, but also include other multiple aspects such as the histological origin of the disease, immunohistochemical manifestations, physiological mechanisms of the disease, hereditary susceptibility and prognostic factors. This article intends to explore how to improve the diagnostic and therapeutic level of adrenal tumors.

Objective:To explore the effect of the isolated organ laparoscopic simulation training teaching mode in laparoscopic partial nephrectomy training.Methods:A 39-hour in vitro organ laparoscopic simulation training for 12 urologists who had previously participated in laparoscopic basic technique training but had not independently completed laparoscopic partial nephrectomy in Peking Union Medical College Hospital. The training was conducted twice a week for 3 months from April to June 2022. Five modules, namely ultrasonic knife separation training, ultrasonic knife cutting training, vascularization training, blunt separation training, and partial nephrectomy and wound closure training, were used to provide targeted training for the decomposition of laparoscopic partial nephrectomy, and each training item was assessed and scored according to the scoring rules. At the same time, a questionnaire was used to find out the level of confidence of the 12 physicians in completing the operation and each step in the procedure, so as to assess the changes in the operational skills and psychological quality of the physicians before and after training using paired t-tests or Wilcoxon paired rank sum tests. Results:After the training, the assessment scores of operations in all surgeons were significantly improved. The training scores of ultrasonic knife separation training, ultrasonic knife cutting training, blood vessel nudity training, blunt separation training, and partial nephrectomy and traumatic suture improved from (8.5±0.3), (6.9±0.3), (4.2±0.4), (6.6±0.4), and (5.6±0.7) to (9.8±0.2), (9.6±0.3), (9.3±0.2), (9.4±0.3), and (9.8±0.2), respectively( P<0.05). The average operation time for the partial renal excision and traumatic suture training improved from (47.5±5.8) minutes to (21.6±5.1) minutes( t=18.72, P<0.001). At the same time, self-confidence in completing the operation was also significantly improved from 2(1, 3) before the training to 4(4, 4) after the training ( Z=-3.002, P =0.003). Conclusions:After laparoscopic simulation training with isolated organs, physicians with no previous experience in partial nephrectomy can become proficient in all steps of the procedure, complete the resection of the renal tumor and suturing of the wound within 30 minutes, and gain confidence in the operation of all steps of partial nephrectomy.

Objective:To investigate the clinical and pathological characteristics of adrenocortical carcinoma (ACC) patients, and to analyze the correlation between clinical features and Ki-67 index.Methods:Retrospectively analyze the clinical data of ACC patients admitted into Peking Union Medical College Hospital from January 1984 to January 2024. Inclusion criteria: ①The patient underwent puncture or surgery, and was diagnosed as ACC; or those who had typical manifestations of adrenocortical multi-band disorders, extremely high FDG uptake in the adrenal area and distant metastasis, and the diagnosis of ACC was considered after multidisciplinary consultation in our hospital; ②The patient had undergone thoracic, abdominal and pelvic CT scan, and could determine the size of the tumor and whether metastasis occurred. Exclusion criteria: ①without pathological diagnosis of ACC or no diagnosis of ACC without multidisciplinary consultation in our hospital; ②no records of symptoms, signs, examinations and other information at the time of initial diagnosis. The baseline data (age, gender, tumor side, etc.), clinical manifestations, endocrine examination, imaging and pathological examination results of the patients were collected, and the relationship between the maximum tumor diameter, the stage of the European Network for the Study of Adrenal Tumors (ENSAT), the functional status of the tumor, the maximum uptake value of 18F-FDG (SUVmax) and the Ki-67 index was analyzed. Results:A total of 164 patients were included in this study. There were 65 males and 99 females, with a male to female ratio of 1∶1.52. The median age at diagnosis was 48 (40, 58) years old. 71 tumors were located (43.29%) on the left side with 91 cases (55.49%) on the right side, and 2 cases (1.22%) on both sides. The median tumor diameter was 9 (7, 12) cm, of which 147 cases (147/158, 93.04%) were>5 cm. A total of 162 patients had ENSAT stages, including 9 stages Ⅰ(5.56%), 72 stage Ⅱ (44.44%), 51 stage Ⅲ (31.48%) and 30 stage Ⅳ(18.52%), respectively. Among the 154 cases with evaluable symptoms, 101 had no typical clinical manifestations and 53 patients had typical clinical manifestations. There were 41 cases (26.62%) of Cushing syndrome, 36 (23.38%) cases of abnormal sexual characteristics, and 19 cases (12.34%) of primary aldosteronism. 100 patients (64.94%) had abnormal endocrine examinations. The results of pathological examination showed 138 cases (90.20%) of traditional subtype, 13 cases (8.50%) of eosinophilic subtype, 1 case of mucinous type (0.65%) and 1 case of sarcomatoid ACC (0.65%). The detection rate of intravascular tumor thrombus was 14.63% (24/164), and the inferior vena cava and renal vein thrombus (10.37, 17/164) were the most common. The median Ki-67 index was 20% (10%, 40%), and 93.13% (122/131) had a Ki-67 index higher than 5%. The median Ki-67 index of ENSAT stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were 20%(10%, 35%), 15%(10%, 30%), 30%(20%, 60%), 30%(20%, 60%), respectively. Compared with stage Ⅱ, ENSAT stage Ⅲ ( P=0.0007) and stage Ⅳ ( P=0.0011) ACC had a higher Ki-67 index; there was no statistical correlation between Ki-67 index and tumor maximum diameter, SUVmax of the primary lesion, and functional status of tumor (all P>0.05). Conclusions:ACC has the characteristics of late staging upon initial diagnosis, low proportion of patients with typical symptoms, and low detection rate of intravascular tumor thrombus. ENSAT stage was correlated with the Ki-67 index. Compared with Stage Ⅱ, ENSAT stage Ⅲ and Ⅳ ACC had a higher Ki-67 index.

Objective:Investigating the efficacy of unilateral adrenalectomy in treatment for primary pigmented nodular adrenocortical disease (PPNAD).Methods:Clinical data of 26 patients with PPNAD treated in our hospital from January 2013 to June 2023 was retrospectively analyzed.There were 11 males and 15 females, with an average age of (19.4±4.7) years. 25 cases presented with typical Cushing's syndrome, and 16 cases were diagnosed with Carney's syndrome. PRKAR1A gene mutation detected in 8 out of 10 cases. CT showed multiple small nodules on bilateral adrenal glands in 14 cases, unilateral small nodules or mild thickening with normal contralateral glands in 8 cases, and no obvious abnormalities in 4 cases. All patients showed autonomous oversecretion of cortisol by endocrine laboratory tests, with a median 24 h-UFC of 408.35 (334.28, 800.78) μg/24 h and decreased level of adrenocorticotropic hormone. All 26 patients underwent laparoscopic unilateral adrenalectomy, with left side adrenalectomy in 8 cases and right side adrenalectomy in 18 cases.Results:The average surgical duration was (85.2±28.7) minutes, with intraoperative blood loss <50 ml in all cases. The median time to drainage tube removal post-operation was 3 (2, 3) days. One patient developed a postoperative pulmonary infection, and 3 patients required postoperative hormone replacement therapy. The median follow-up duration was 64 (31.5, 103.8) months, and all patients showed alleviation of Cushing syndrome clinical manifestations after operations. 19 patients (73.1%) had their 24 h-UFC levels normalized to a median of 42.0 (22.4, 58.3) μg/24 h within 8.5 (5, 46) days post-surgery. 7 patients (26.9%) did not achieve normal 24 h-UFC levels, yet experienced an average reduction of (73.2±10.4)%. 13 patients (50.0%) did not experience recurrence, with a median follow-up of 51 (7, 89.5) months, including two cases without recurrence at 10 years post-surgery. 13 patients showed recurrent increase in postoperative cortisol levels, with a median of 225.6 (188.9, 397.2) μg/24 h. The median time to increased 24 h-UFC post-surgery was 27 (13.5, 50.5) months, with the longest duration reaching 104 months. Among these, 9 cases exhibited clinical signs and symptoms of recurrence, while 4 cases did not. Of the 13 patients with recurrence, 9 underwent contralateral adrenalectomy or subtotal resection, while 4 were observed with follow-up.Conclusions:Unilateral adrenalectomy could be a surgical treatment option for PPNAD. Despite the recurrence in some patients postoperatively, unilateral adrenalectomy could effectively and rapidly reduce cortisol levels in PPNAD patients and alleviate the clinical manifestations of Cushing syndrome.

Objective:To explore the value of nuclear proliferation index (MIB-1) in the diagnosis and prognosis of adrenal cortical carcinoma (ACC).Methods:A retrospective analysis was conducted on the clinical data of ACC patients and patients with benign adrenal lesions admitted to Beijing Union Medical College Hospital from June 2018 to August 2022. There were 59 cases in the ACC group, 25 males and 34 females, with a male to female ratio of 1∶1.4. Age (46.1 ± 2.1) years old, including 4 cases under 20 years old, 7 cases between 21-30 years old, 11 cases between 31-40 years old, 14 cases between 41-50 years old, 13 cases between 51-60 years old, 8 cases between 61-70 years old, and 2 cases over 70 years old. Body mass index (24.3 ± 2.4) kg/m 2. Systolic blood pressure (149.3 ± 5.2) mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure (93.4±1.7) mmHg. There were 51 cases of typical Cushing's syndrome, 52 cases of hypertension, 44 cases of elevated blood sugar, 16 cases of hypokalemia, and 16 cases of menstrual abnormalities and acne caused by androgen secretion. Laboratory examination: Blood glucose (7.2 ± 0.3) mmol/L, glycated hemoglobin (8.6 ± 1.4)%, total cholesterol (5.7 ± 0.3) mmol/L, and triglycerides (2.0 ± 0.3) mmol/L. 24-hour urine free cortisol (234.4 ± 39.0)μg/24 h, with 46 cases showing an increase, and at 8am, corticotropin releasing hormone (9.5 ± 4.1) pg/ml, with 48 cases showing a decrease. Blood free cortisol (401.2 ± 17.1)μg/dl, with 42 cases of rhythm disappearance. 17 cases showed elevated aldosterone levels. Dehydroepiandrosterone sulfate (713 ± 159)μg/dl, of which 16 cases increased. Neuroenolase (21.2 ± 5.3) ng/ml, of which 27 cases were elevated. Insulin like growth factor-1 was (272.0 ± 42.1) ng/ml, with 26 cases showing an increase. 46 routine high-dose and low-dose dexamethasone inhibition tests were not suppressed. 39 cases of tumors were functional. 59 cases underwent preoperative abdominal and pelvic contrast-enhanced CT, MRI, and B-ultrasound examination, and 21 cases underwent PET/CT examination. The tumors were located in 32 cases on the left, 26 cases on the right, and 1 case on both sides. The maximum diameter of the tumor was (9.6 ± 1.7) cm, with 43 cases ≤10 cm and 16 cases >10 cm. There were 5 cases with lymph node metastasis, 16 cases with distant metastasis, and 11 cases with local invasion. There were 4 cases of tumor ENSAT clinical staging stage Ⅰ(T 1N 0M 0 stage), 27 cases of stage Ⅱ(T 2N 0M 0 stage), 23 cases of stage Ⅲ(T 1-2N 1M 0 stage, T 3N 0M 0 stage), and 5 cases of stage Ⅳ(T 1-4N 0-1M 1 stage, T 3N 1M 0 stage, T 4N 0-1M 0 stage). Six cases were accompanied by tumor thrombi in the central adrenal vein, renal vein, and inferior vena cava. There were 53 cases of benign adrenal tumors, including 26 males and 27 females. Age (44.3±3.2) years old, typical manifestations of Cushing's syndrome in 28 cases, 24-hour urine free cortisol (176.4±41.2) μg/24 h. 27 cases showed disappearance of free cortisol rhythm. Dehydroepiandrosterone sulfate is normal. 23 routine high-dose and low-dose dexamethasone inhibition tests were not inhibited. The maximum diameter of the tumor is (4.2 ± 2.3) cm. T 1N 0M 0 stage patients undergo robotic or laparoscopic radical adrenalectomy, with the resection range including the surrounding lymphoid tissue of the tumor; Patients with stage ≥T 2 underwent open radical adrenalectomy and lymph node dissection. Six cases underwent radical adrenalectomy combined with nephrectomy due to tumor invasion of the kidneys with unclear boundaries. 11 cases of local implant metastasis underwent stereotactic radiotherapy. Nine patients with liver metastasis underwent Interventional Embolization treatment. Three cases with isolated lung metastases underwent surgical resection. Four cases of multiple lung metastases were treated with radiotherapy combined with mitotane. According to the postoperative pathological examination results, record the pathological Weiss score and MIB-1. Analyze the correlation between MIB-1 and clinical pathological indicators and prognosis of patients. Results:There were 59 cases in the ACC group, 35 cases of R0 resection, 19 cases of R1 resection and 5 cases of R2 resection.The postoperative pathological examination showed an average weight of approximately (371±52)g, with 42 cases having a tumor mass ≤ 300 g and 17 cases having a tumor mass>300 g. The positive rate of MIB-1 in the control group was 1% to 5%, while the positive rate of MIB-1 in the ACC group was greater than 5%, the difference between the two groups was statistically significant ( P<0.01). 53 patients diagnosed with capsule invasion, capsule rupture, intravascular tumor thrombus, and MIB-1>10% through postoperative pathological examination were treated with tumor bed radiotherapy and mitotan medication, followed by second-line combination immunotherapy and EDP chemotherapy. The 5-year survival rates of ACC patients with different tumor stages were 65% in stage Ⅰ, 58% in stage Ⅱ, 38% in stage Ⅲ, and less than 5% in stage Ⅳ. The total survival time of the two subgroups with low and high staging was 3.6 years and 1.1 years respectively ( P=0.003), while the disease-free survival time of the two groups was 25 months and 11 months, respectively ( P=0.011). R0 resection has a better prognosis than R1 and R2 resection, and its five-year survival rate is higher ( P=0.03). The 5-year survival rates of R0, R1, and R2 groups were 61%, 31%, and 17%, respectively( P=0.030).Survival analysis showed that adrenal cortical cancer patients with MIB-1 greater than 10% had a worse prognosis, with 5-year OS of 17% and 32% for both groups, respectively ( P=0.021). The Weiss score of the ACC group was (7±2). There were 21 cases in the Weiss score 3-5 group and 38 cases in the 6-9 group, the 5-year survival rates of the two groups were 62% and 19%, respectively ( P=0.017). Conclusions:MIB-1 can serve as an auxiliary diagnostic and prognostic indicator, and high expression of MIB-1 can contribute to the early diagnosis and determination of treatment strategies for ACC.

Objective To explore the beneficial effects and mechanisms of neutrophil elastase (NE) and myeloperoxidase (MPO) on lead-induced hepatic inflammation in mice. Methods The specific pathogen free male C57BL/6 mice were randomly divided into four groups： control group, lead-exposed group, NE inhibitor group, and MPO inhibitor group, with three mice in each group. The mice in lead-exposed group, NE inhibitor group, and MPO inhibitor group were intraperitoneally injected with a dose of 10 mg/kg body mass of lead acetate solution, while the mice of control group received an equal volume of 0.9% saline three times per week for four weeks. In the last seven days, mice in both inhibitor groups were intraperitoneally injected with a dose of 40 mg/kg NE inhibitor sivelestat sodium or MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) once per day. Mouse body weight and liver histopathological changes were observed. The mRNA expression of genes associated with inflammation, such as tumor necrosis factor-α (Tnfa), interleukin-1β (Il1b), interleukin-6 (Il6), and nucleotide-binding oligomerization domain-like receptor protein 3(Nlrp3), apoptosis-associated speck-like protein (Asc) and cysteinyl aspartate specific proteinase (Caspase1) in the mouse liver tissues was detected by real-time quantitative polymerase chain reaction. The protein expression of NLRP3, ASC, and CASPASE-1 was detected using Western blotting. Results The activities of mice in all four groups were generally normal, and there was no significant difference in body weight (P>0.05). The results of hematoxylin-eosin staining showed that the cell size of hepatocytes varied in the lead-exposed mice, with indistinct cell boundaries, indicating early inflammatory responses in liver tissues. After intervention with NE or MPO inhibitors, the early inflammatory responses improved in the liver tissues of the mice in both inhibitor groups, with a better improvement observed in MPO inhibitor group compared with the NE inhibitor group. The mRNA expression of Tnfa, Il1b, Il6, Nlrp3, Asc, and Caspase1, as well as the protein expression of ASC, and CASPASE-1 in the livers of mice in the lead-exposed group was higher compared with those in the control group (all P<0.05). Compared with the lead-exposed group, the relative mRNA expression of Tnfa, Il1b, Il6, Nlrp3 and Asc was decreased in the liver tissues of mice in the NE inhibitor group (all P<0.05), while the relative expression of mRNA of Tnfa, Il1b, Il6, Caspase1 and the protein expression of ASC and CASPASE-1 were decreased in the liver tissues of mice in the MPO inhibitor group (all P<0.05). Conclusion Lead induce hepatic inflammation in mice by activating NLRP3 inflammasome. The inhibition of NE or MPO improve the lead-induced hepatic inflammatory responses in mice by alleviating NLRP3 inflammasome activation.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS^E） technique， we identified qualitatively the metabolites of aristolochic acid（AAs） in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus（AFE） and Aristolochic acid Ⅰ（AAⅠ）. MethodSD rats were selected and administered AFE（110 g·kg^-1·d^-1） or AAⅠ（5 mg·kg^-1·d^-1） by oral for 5 days， respectively. Serum， urine and feces were collected after administration. Through sample pretreatment， ACQUITY UPLC BEH C₁₈ column（2.1 mm×100 mm， 1.7 μm） was used with the mobile phase of 0.01% formic acid methanol（A）-0.01% formic acid water（B， containing 5 mmol·L^-1 ammonium acetate） for gradient elution（0-1 min， 10%B； 1-7 min， 10%-75%B； 7-7.2 min， 75%-95%B； 7.2-10.2 min， 95%B； 10.2-10.3 min， 95%-10%B； 10.3-12 min， 10%B） at a flow rate of 0.3 mL·min^-1. Positive ion mode of electrospray ionization（ESI⁺） was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system， the Pathway-MS^E was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples（serum， urine and feces）， and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group， 6， 10， 13 common metabolites and 14， 20， 30 unique metabolites were identified in biological samples（serum， urine and feces） of AFE group， respectively. Moreover， the main AAs components always followed the metabolic processes of demethylation， nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group， prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ［AAⅠa， aristolochic lactam Ⅰ（ALⅠ）a， 7-OHALⅠ and its conjugated derivatives］ in biological samples were significantly increased in AFE group（P<0.05， P<0.01）， except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group（P<0.01）. In addition， a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo， the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ， and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.