Case report: Rare case of a preoperatively diagnosed spermatic cord paraganglioma and literature review.

Paraganglioma (PGL) is rare, and PGL that arises from the urogenital system is even rarer. Here we report a case of PGL in spermatic cord and review the relevant literatures. We encountered a 15-year-old boy with a history of hypertension for almost 2 years, accompanied with headache and palpitations. His serum and urine catecholamines were elevated, but no adrenal lesions were detected, suggesting the existence of PGL. Upon physical examination, a painless nodule adherent to the spermatic cord in the right scrotum was found. A systemic Ga68 DOTATATE PET-CT was then performed, and it revealed a mass with high DOTATATE uptake in the right scrotum. The CT, MRI, and ultrasound images showed the abundant blood supply to the tumor. Based on the above-mentioned imaging and biochemical information, a diagnosis of PGL was made prior to surgery. After 2 weeks of preparation with Cardura, an open surgery was performed to remove the tumor together with the right testis and right epididymis. The blood pressure increased to 180/100 mmHg when the tumor was touched intraoperatively and decreased to 90/55 mmHg after the tumor was removed. Post-operative pathology confirmed our diagnosis of PGL originating from the spermatic cord. Immunohistochemical (IHC) staining showed SDHB (+), CgA (+), synaptophysin (+), GATA3 (+), CD56 (+), sertoli cells S-100 (+), and Ki67 (5%). Genetic testing revealed a missense mutation in the SDHA gene. Only 16 cases of spermatic cord PGL have been reported to date. Although it is easy to diagnose by histology and IHC examinations, preoperative diagnosis is quite important as it can actually reduce intraoperative complications.

HIF1A transcriptional regulation of COX4I2 impacts angiogenesis in pheochromocytoma.

BACKGROUND: Pheochromocytoma (PCC) is a rare neuroendocrine tumor. Angiogenesis is primary contributing factor for tumorigenesis. Cytochrome c oxidase 4I2 (COX4I2) has been confirmed to take part in the progression of cancer. Hypoxia-inducible factor 1A (HIF1A) is the main regulatory factor for the steady-state response of hypoxia, involved in metabolism and angiogenesis. In this study, we intended to explore the functions of COX4I2 in PCC and the effect mechanism between HIF1A and COX4I2. MATERIALS AND METHODS: The RNA-sequencing and immunohistochemistry tested COX4I2 expression in highly vascular PCC. Small interfering RNA (siRNA) was used to reduce the mRNA expression of COX4I2, and a small molecule inhibitor was utilized to reduce the protein expression of HIF1A. Culturing cells in 1% O2environment was performed to activate HIF1A. Western blot was applied to quantify the expression of target genes at the protein levels. The supernatant from PCC cells and fibroblasts acted as the conditioned medium. We conducted the tube formation and transwell assays in human vascular endothelial cells (HUVECs) to determine angiogenesis, the binding of COX4I2 promoter and HIF1A was evaluated by the dual luciferase reporter assay. RESULTS: COX4I2 had been rigorously shown to be overexpressed in highly vascular PCC. Knockdown of COX4I2 in PCC cells (MPC) did not significantly impact angiogenesis, while knockdown of COX4I2 in fibroblast (3T3) notably inhibited angiogenesis. RNA sequencing suggested that the expression of 11 vascular markers, such as CD34 and angiogenesis associated pathways in 3T3, decreased with knockdown of COX4I2. HIF1A had been shown to enhance the mRNA expression of COX4I2 through transcriptional regulation. Activation and inhibition of HIF1A resulted in upregulation and downregulation of COX4I2, respectively. The HIF1A inhibitor demonstrated a reduction in angiogenesis. CONCLUSION: COX4I2 is overexpressed in highly vascular PCC and contributes to angiogenesis in fibroblasts. Mechanistically, HIF1A transcriptional regulation enhances COX4I2 and its effects on angiogenesis in PCC. COX4I2 might serve as a vascular marker and represent a potential target for vascular therapy.

A novel fault diagnosis strategy for LED lamps via light output time-frequency characteristics analysis and machine learning.

Faulty LED lamps can cause a decrease in light efficiency, lead to flicker, and have a negative impact on creating a reliable, stable, and healthy light environment. However, many LED lamps' faults are difficult to detect by electrical parameter measurements or naked-eye observation. Consequently, in this paper, a novel fault diagnosis strategy is proposed by analyzing light output time-frequency characteristics of LED lamps. The proposed fault diagnosis strategy contains three stages: (1) collecting the light output signal of LED lamps, (2) extracting the light output time-frequency characteristics of LED lamps by VMD and energy entropy calculation, and (3) employing SVM to construct the fault diagnosis model which used to identify the faulty LED lamps. To validate the feasibility and effectiveness of the proposed fault diagnosis strategy, simulation experiments are conducted, and the light output signals of LED lamps are collected as experiment datasets using the 10 kHz sampling frequency. The results demonstrate that the proposed fault diagnosis strategy can identify faults effectively, and average accuracy rate can reach to over 92%. This study can help promote the development of large-scale LED lamp maintenance management technology, and bring great benefits for the reliable and healthy operation of large-scale LED lamps particularly.

Surgery based on computed tomography images might be feasible for primary aldosteronism patients with visible unilateral adenoma.

Primary aldosteronism (PA) with unilateral adrenal disease can be cured or improved by adrenalectomy. Adrenal venous sampling (AVS) is recommended to identify patients for surgical management. However, surgeries based on computed tomography (CT) images are only advocated for PA patients aged <35 with visible unilateral adenoma. Herein, we aimed to compare CT-based and AVS-based surgery outcomes for PA patients with visible unilateral adenomas for different age groups. A total of 178 PA patients who underwent unilateral adrenalectomy between June 2018 and January 2021 were included in the study based on CT (n = 54) or AVS (n = 124). Demographics, diagnostics, and follow-up data were retrospectively collected. Clinical and biochemical outcomes were analyzed according to Primary Aldosteronism Surgical Outcome (PASO) criteria at 1-year follow-up. Our results showed that complete clinical success (46.3% vs. 47.6%, p = 0.875) and complete biochemical success (88.8% vs. 91.9%, p = 0.515) were similar between the two groups. Age stratification revealed that patients >55 years old were likely to have worse biochemical outcomes; however, these were still not significantly different (21.4% vs. 8.6%, p = 0.220). Of the 114 AVS-based patients who achieved complete biochemical success, 37 (32.4%) with bilateral normal or bilateral abnormal CT images changed treatment options according to AVS results, 1 (0.9%) avoided adrenalectomy on the wrong side. Our results indicated that surgery based on CT images might be feasible for highly selected PA patients with visible unilateral adenomas and less limited by age, while for those with normal adrenal or bilateral adrenal lesions, treatment strategy must be decided by AVS.

Forkhead box F1 functions as a novel prognostic biomarker and induces caspase­dependent apoptosis in bladder cancer.

The downregulated expression of forkhead box F1 (FOXF1) has been found in many malignant tumors but no research was done in bladder cancer (BC). The present study aimed to investigate the prognostic value and antitumor effects of FOXF1 in patients with BC. Herein, a retrospectively recruited BC cohort and public datasets were utilized to identify the predictive ability of FOXF1 and determine its association with the clinical characteristics of BC patients. It was found that the expression level of FOXF1 was notably lower in BC tissues than in para­cancerous mucosae. Low FOXF1 expression was associated with unfavorable clinicopathological features and poor prognosis. Furthermore, in BC cells, the mRNA and protein expression levels of FOXF1 were examined using reverse transcription­quantitative PCR and western blot analysis. Cell viability was examined using Cell Counting Kit­8, EdU and clonogenic capacity assays. Cell apoptosis was detected using flow cytometry. The results revealed that the activation of FOXF1 impaired cell viability and induced apoptosis in BC. The antitumor effects of FOXF1 were also validated using animal models. Subsequently, caspase­3 was spotted as a downstream gene of FOXF1 by using RNA sequencing and protein­protein interaction analyses. FOXF1 inhibited proliferation and induced apoptosis of BC cells via caspase signaling pathway. The present study demonstrates the expression patterns, prognostic predictive ability and antitumor effects of FOXF1 in BC. FOXF1 is a favorable biomarker for predicting clinical outcomes in patients with BC and represents a potential therapeutic target.

MicroRNA-30c-5p arrests bladder cancer G2/M phase and suppresses its progression by targeting PRC1-mediated blocking of CDK1/Cyclin B1 axis.

BACKGROUND: MicroRNAs (miRNAs) play a critical role in cancer development and progression, the dis-regulation of miR-30c-5p has been observed in various malignant tumors but no research was done in bladder cancer (BCa). This study aims to investigate the downregulation of miR-30c-5p in BCa, and examine its mechanism and prognostic significance. METHODS: Bioinformatics analyses and clinical specimens were employed to investigate the relationship between miR-30c-5p and clinical information in BCa patients. The expression levels of miR-30c-5p and its target gene were assessed by real-time PCR and western blot. Cell viability was evaluated through clonogenic capacity, CCK-8, and EdU assays. Cell cycle distribution and cell apoptosis were determined by flow cytometry. The anti-tumor effect of miR-30c-5p was also validated in animal models. RESULTS: The expression levels of miR-30c-5p were significantly decreased in both bladder tumor tissue and BCa cell lines. Low miR-30c-5p expression was found to be correlated with unfavorable TNM stages and poor prognosis. Over-expressing miR-30c-5p was observed to hinder BCa cell growth, migration, and invasion abilities and causing cell cycle arrest. Mechanistically, miR-30c-5p directly binds and suppresses PRC1, thereby blocking the CDK1/Cyclin B1 axis in BCa, thus impairing BCa cell viability and inducing cell cycle arrest at G2/M phase. CONCLUSION: Down-regulated miR-30c-5p promotes BCa through its target gene PRC1, miR-30c-5p is a favorable biomarker for predicting clinical outcomes in BCa patients and has the potential to be a therapeutic target.

Artificial intelligence with a deep learning network for the quantification and distinction of functional adrenal tumors based on contrast-enhanced CT images.

Background: Functional adrenal tumors (FATs) are mainly diagnosed by biochemical analysis. Traditional imaging tests have limitations and cannot be used alone to diagnose FATs. In this study, we aimed to establish an artificially intelligent diagnostic model based on computed tomography (CT) images to distinguish different types of FATs. Methods: A cohort study of 375 patients diagnosed with hyperaldosteronism (HA), Cushing's syndrome (CS), and pheochromocytoma in our center between March 2015 and June 2020 was conducted. Retrospectively, patients were randomly divided into three data sets: the training set (270 cases), the testing set (60 cases), and the retrospective trial set (45 cases). An artificially intelligent diagnostic model based on CT images was established by transferring data from the training set into the deep learning network. The testing set was then used to evaluate the accuracy of the model compared to that of physicians' judgments. The retrospective trial set was used to evaluate the quantification and distinction performance. Results: The deep learning model achieved an average area under the receiver operating characteristic (ROC) curve (AUC) of 0.915, and the AUCs in all three FAT types were greater than 0.882. The AUC of the model tested on the retrospective dataset reached above 0.849. In the quantitative evaluation of tumor lesion area recognition, the diagnostic model also obtained a segmentation Dice coefficient of 0.69. With the help of the proposed model, clinicians reached 92.5% accuracy in distinguishing FATs, compared to 80.6% accuracy when using only their judgment (P<0.05). Conclusions: The result of our study shows that the diagnostic model based on a deep learning network can distinguish and quantify three common FAT types based on texture features of contrast-enhanced CT images. The model can quantify and distinguish functional tumors without any endocrine tests and can assist clinicians in the diagnostic procedure.

The effect of unilateral adrenalectomy on patients with primary bilateral macronodular adrenal hyperplasia.

PURPOSE: To evaluate the long-term effect of unilateral adrenalectomy (uADX) on patients with primary bilateral macronodular adrenal hyperplasia (PBMAH). METHODS: We retrospectively reviewed 29 patients (including 11 men and 18 women) with PBMAH and Cushing's syndrome (CS) between 2005 and 2019 who underwent uADX in our center. Clinical symptoms, serum cortisol (8:00 a.m., 4:00 p.m., and 0:00 a.m.), 24 h urinary free cortisol (UFC), computed tomography (CT) scan of the adrenal gland, and pituitary nuclear magnetic resonance (MR) scan performed before and after operation were analyzed. RESULTS: The median follow-up time was 39 (13-134) months. uADX decreased significantly at 24 h UFC (median: 357.14 vs. 89.50 ug/24 h, P < 0.001) and serum cortisol (8:00 a.m.) (median: 22.88 vs. 12.50 ug/uL, P < 0.001) 1 year after surgery. In total, 17 of 29 patients had normal UFC again 1 year after surgery, while one of them suffered a relapse after 61 months. However, uADX failed to decrease UFC to the normal range in the other patients. Ten of the remaining 12 uncured patients and the relapsed patient finally underwent contralateral adrenalectomy (cADX). The 24 h UFC of the patients who were cured (n = 17) after uADX was significantly lower than that of the uncured patients (n = 12) (222.30 vs. 579.10 ug/24 h, P = 0.011). CONCLUSION: uADX may be an appropriate treatment for patients with mildly elevated cortisol, while contralateral adrenalectomy (cADX) may be required for patients with highly elevated cortisol. The level of 24 h UFC is helpful to predict patients' prognosis.

Fibroblasts mediate the angiogenesis of pheochromocytoma by increasing COX4I2 expression.

Objective: Our previous work found COX4I2 was associated with angiogenesis in pheochromocytoma. The purpose of this study was to explore the role of COX4I2 in regulating angiogenesis in pheochromocytoma. Methods: Distribution of COX4I2 was evaluated by scRNA-seq in one case of pheochromocytoma and the findings were verified by immunostaining. COX4I2 was further knocked down in target cells. Changes of angiogenesis-related genes were evaluated by qPCR in target cells. Results: The scRNA-seq revealed high mRNA expression of COX4I2 in fibroblasts rather than tumor cells. Immunostaining of COX4I2 confirmed its distribution in fibroblasts. Knocking down COX4I2 in NIH3T3 cell line led to significant reduction of angiogenesis-related genes, especially ANG1 and HGF. Conclusions: Fibroblasts mediate the angiogenesis of pheochromocytoma by increasing COX4I2 expression, possibly by affecting ANG1 and HGF.

The Relationship Between Baseline Cortisol Levels and Surgery Method of Primary Bilateral Macronodular Adrenal Hyperplasia.

Aim was to explore the associations between baseline cortisol levels and surgery method of primary bilateral macronodular adrenal hyperplasia (PBMAH). We retrospectively reviewed the clinical features and management of 30 patients (18 females and 12 males) who were diagnosed with PBMAH in our center between 2005 and 2019. Based on surgery method, we divided the patients into two groups: unilateral adrenalectomy (UA) group; and bilateral adrenalectomy (BA) group. Serum cortisol rhythm and 24-hour urinary free cortisol (UFC/24 h) levels were assayed using chemiluminescence method. Associations between baseline cortisol levels and BA were assessed using logistic regression. The predictive value of baseline cortisol levels for BA was calculated using receiver operating characteristic (ROC) curves. Twenty patients (66.7%) underwent UAs and ten patients (33.3%) underwent BAs. After adjusting for age, sex, BMI, SBP, and adrenal volume, the concentrations of baseline serum cortisol (8 AM, 4 PM, and 0 AM) and UFC/24 h were associated with bilateral adrenalectomy (all p<0.05). The area under the ROC curve based on 8 AM serum cortisol level model was larger than that in models based on 4 PM, 0 AM serum cortisol levels and UFC/24 h, but the differences were non-significant (all p>0.05). According to maximum Youden index criteria, the optimal cutoffs of 8 AM serum cortisol level and UFC were 26.89 µg/dl and 406.65 µg/24 h, respectively, for BA. The baseline cortisol levels are positively associated with BA. Increased levels of baseline cortisol levels may predict higher possibility of BA, which should be confirmed by prospective studies.

S-GRAS score performs better than a model from SEER for patients with adrenocortical carcinoma.

Purpose: To externally validate the performance of the S-GRAS score and a model from the Surveillance, Epidemiology, and End Results (SEER) database in a Chinese cohort of patients with adrenocortical carcinoma (ACC). Methods: We first developed a model using data from the SEER database, after which we retrospectively reviewed 51 ACC patients hospitalized between 2013 and 2018, and we finally validated the model and S-GRAS score in this Chinese cohort. Results: Patient age at diagnosis, tumor size, TNM stage, and radiotherapy were used to construct the model, and the Harrell's C-index of the model in the training set was 0.725 (95% CI: 0.682-0.768). However, the 5-year area under the curve (AUC) of the model in the validation cohort was 0.598 (95% CI: 0.487-0.708). The 5-year AUC of the ENSAT stage was 0.640 (95% CI: 0.543-0.737), but the Kaplan-Meier curves of stages I and II overlapped in the validation cohort. The resection status (P = 0.066), age (P=0.68), Ki67 (P = 0.69), and symptoms (P = 0.66) did not have a significant impact on cancer-specific survival in the validation cohort. In contrast, the S-GRAS score group showed better discrimination (5-year AUC: 0.683, 95% CI: 0.602-0.764) than the SEER model or the ENSAT stage. Conclusion: The SEER model showed favorable discrimination and calibration ability in the training set, but it failed to distinguish patients with various prognoses in our institution. In contrast, the S-GRAS score could effectively stratify patients with different outcomes.

The circular RNA circFARSA sponges microRNA-330-5p in tumor cells with bladder cancer phenotype.

BACKGROUND: Circular RNAs (circRNAs) modulate gene expression in various malignancies. However, their roles in the occurrence of bladder cancer (BC) and their underlying mechanisms of action are currently unclear. METHODS: We measured levels of the circRNA phenylalanyl-tRNA synthetase subunit alpha (circFARSA) and target microRNAs (miRNAs/miRs) in BC tissues and cell lines using quantitative polymerase chain reactions. The functions of circFARSA in tumor formation were examined in mice with BC xenografts in vivo and in BC cells via determination of their proliferation, activity, apoptosis, metastasis, and invasion in vitro using cell counting kit-8 assays, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, flow cytometry, western blotting, Transwell assays, and cell wound healing assays. Interactions between miR-330 and circFARSA were predicted and confirmed by bioinformatic processing and dual-luciferase reporter gene assays, respectively. Expression profiles of miR-330 targets in BC cells were assessed via western blotting. RESULTS: circFARSA expression was markedly upregulated in BC tissues and cell lines compared with that in normal bladder samples. Silencing circFARSA expression decreased BC cell proliferation, invasion, and migration but induced their apoptosis in vitro. Downregulating circFARSA expression slowed tumor growth in vivo and directly sponged miR-330 and inhibited its function in BC cells in vitro. Inhibiting miR-330 expression abolished the regulatory effects of circFARSA silencing on the tumor phenotypes of BC cells. CONCLUSIONS: circFARSA expression is upregulated and exerts oncogenic functions in BC by sponging miR-330.

An 8-year clinical experience with diagnosis and treatment of adrenal lesions with calcification.

Adrenal lesions with calcification are uncommon and surgical indication remains controversial. We evaluate rational indications for surgical intervention of adrenal lesions with calcification. From 2013 to 2021, 75 adrenal lesions with calcification managed with surgery had necessary studies for evaluation of rational surgical indication. Clinical benefit was defined as relief of symptoms or/and removal of the malignant tumors. Influencing factors for clinical benefit were evaluated by logistic regression. During the past 8-year period, 5057 patients received adrenal surgery in our center and 75 (1.5%) patients were accompanied with calcification, including 34 males and 41 females with a median age of 54 years (IQR = 41-63 years). The median maximum diameter of calcified adrenal lesions on preoperative CT imaging was 4.2 cm (IQR = 3.0-5.9 cm). Clinical benefit was achieved in 22 cases, including 4 cases of malignant tumors and 18 cases of relieved clinical symptoms. Correlation analysis indicated that maximum diameter of the lesion was significantly correlated with clinical benefit (p = 0.025). The maximum diameter in benefit group vs. non-benefit group was 5.5 cm (IQR = 3.7-7.4 cm) vs. 3.7 cm (IQR = 2.8-5.4 cm). AUC of the maximum diameter ROC curve of adrenal lesions was 0.662. The diameter, sensitivity and specificity corresponding to the maximum Youden index value were 4.5 cm, 0.682 and 0.623, respectively. Clinical benefit was not significantly correlated with calcification distribution (peripheral or internally scattered) (P = 0.106), calcification area ≥ 50% (P = 0.617) and internal enhancement of the lesion (P = 0.720). Adrenal lesions with calcification are mostly benign. Clinical benefit is significantly correlated with the maximum diameter of the lesion and 4.5 cm may be considered as the cutoff point of surgical intervention.

High TNFSF13B expression as a predictor of poor prognosis in adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is an extremely rare malignant tumor with poor prognosis. Existing treatment options have limited effects, and new therapeutic targets urgently need to be discovered. TNFSF13B has been reported to be associated with the prognosis of clear cell renal cell carcinoma, but it has not been studied in ACC. METHODS: TNFSF13B expression was analyzed and compared between ACC tumors and normal tissues by using public datasets from TCGA and GTEx. Kaplan-Meier analysis was employed to evaluate survival, and Cox regression was employed to evaluate clinicopathologic features. The upstream and downstream regulatory mechanisms of TNFSF13B were also analyzed. GSEA was performed to explore the mechanisms of TNFSF13B in ACC. Finally, 14 ACC clinical samples were used to verify the relationships between TNFSF13B expression and disease-free survival (DFS) and overall survival (OS). RESULTS: TNFSF13B expression was significantly higher in ACC tissues than in normal tissues. The prognosis of ACC patients with high TNFSF13B expression was worse than that of patients with low TNFSF13B expression. High TNFSF13B expression was strongly correlated with poor prognosis, and TNFSF13B was a prognostic factor. TNFSF13B expression is modified by upstream miRNAs, methylation and ubiquitination, and downstream, it interacts with other proteins. GSEA showed that regulation of cholesterol biosynthesis by SREBP and SREBF, downstream signaling events of the B cell receptor (BCR) and activation of gene expression by SREBF and SREBP were significantly enriched in the TNFSF13B high-expression phenotype. Clinical samples confirmed that TNFSF13B expression was significantly associated with DFS but not with OS. CONCLUSIONS: TNFSF13B may be a potential prognostic molecular marker of poor survival in ACC patients, offering a new therapeutic target.

Case Report: Rare Case of Synchronous Neck Metastasis From Metachronous Bilateral Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is a malignant tumor that can metastasize easily. Hence, many patients have already developed metastasis when they are diagnosed. It is also one of the most common tumors that metastasize to the head and neck through extranodal disease. Herein, we reported a case of a 53-year-old man with cervical metastasis from bilateral RCC. Interestingly, whole exome sequencing (WES) and clonal evolution analysis revealed that bilateral renal tumor lesions and neck metastases (squamous cell carcinoma) share the same subclones and a large number of gene variants, while the pathological morphology is different (left nephrotic foci, a mixed pattern of mucinous tubular and spindle cell carcinoma (MTSCC) with papillary adenoma; right renal foci, papillary renal cell carcinoma (PRCC)). This was first reported in RCCs to the best of our knowledge. This case suggests that genotype analysis can be a powerful supplementary examination for clinical histopathological diagnosis. Gene detection has great significance for the accurate diagnosis and treatment of RCC metastasis or multiple lesions.

A circular RNA, circSMARCA5, inhibits prostate cancer proliferative, migrative, and invasive capabilities via the miR-181b-5p/miR-17-3p-TIMP3 axis.

SMARCA5 (circSMARCA5) is involved in the occurrence of different cancers, but its role in prostate cancer carcinogenesis and metastatic transformation remains elusive. Thus, we evaluated the circSMARCA5 functional relevance in prostate cancer and its associated molecular mechanism. First, circSMARCA5 expression and function in this cancer were evaluated. To determine the miR-181b-5p/miR-17-3p target and clarify how circSMARCA5 regulates the miR-181b-5p-TIMP3 and miR-17-3p-TIMP3 axis, RNA immunoprecipitation, biotin-coupled microRNA capture, luciferase reporter, Western blot, and quantitative real-time PCR assays were employed. In primary and metastatic prostate cancer tissues, circSMARCA5 was significantly downregulated compared with normal controls. Functionally, circSMARCA5 exhibited a suppressive effect on prostate cancer cells' metastasis and growth. At the molecular level, circSMARCA5 could affect the tissue inhibitor of metalloproteinases 3 (TIMP3) expression through miR-181b-5p or miR-17-3p interactions. Moreover, lysine acetyltransferase 5 (KAT5) induced circSMARCA5 biogenesis and regulated the miR-181b-5p-TIMP3 and miR-17-3p-TIMP3 axis. These results suggested that targeting circSMARCA5-miR-181b-5p-TIMP3 and circSMARCA5-miR-17-3p-TIMP3 axis might be a novel therapeutic strategy for prostate cancer.

COX4I2 is a novel biomarker of blood supply in adrenal tumors.

BACKGROUND: Previous study has been reported that COX4I2 expression level demonstrated a positive correlation with microvessel density in pheochromocytomas (PCC) samples, suggesting that the expression of COX4I2 maybe related to blood supply level in other adrenal tumors as well. The aim of this study is to clarify the correlation of COX4I2 expression and blood supply in adrenal tumors. METHODS: A total of 84 patients were recruited, among which 46 was diagnosed as adrenocortical adenoma (ACA) and 38 was diagnosed as PCC. Contrast-enhanced CT values were used to evaluate the blood supply levels in those patients. The expression of mRNA was examined by quantitative real-time polymerase chain reaction (qPCR) and protein was detected by immunohistochemistry (IHC). RESULTS: The COX4I2 expression level in PCC group is significantly higher than that in ACA group (P<0.01). The expression of angiogenesis-related genes EPAS1, VEGFA and KDR mRNA in PCC group is higher than that of ACA group (P<0.05). Correlation analysis shows COX4I2 expression level is correlated with CT values (P<0.001), intraoperative blood loss (P<0.05) and operation time (P<0.05), and the expression of COX4I2 mRNA is correlated with EPAS1, VEGFA and KDR mRNA (P<0.01). CONCLUSIONS: The results displayed a distinct expression level of COX4I2 between ACA and PCC, suggesting that COX4I2 is a novel biomarker of blood supply in adrenal tumors. This research also opens the possibility for further research on COX4I2 as a novel target for anti-tumor angiogenesis.

Primary malignant teratoma of the kidney: a rare case report and literature review.

Teratomas originate from pluripotent cells and can differentiate along one or more embryonic germ lines. Renal teratoma is infrequent and malignant renal teratoma is even rarer. Experience in the diagnosis and treatment of this uncommon malignancy is seriously limited. In this report, we described the case of a 64-year-old female who complained of right flank pain for 4 months. Computed tomography (CT) revealed a hypodense mass (50 mm in maximum diameter) with slow contrast enhancement and obscure boundary located in the lower pole of the right kidney. CT also showed multiple retroperitoneal lymphadenectasis. Retroperitoneal laparoscopic right radical nephrectomy along with regional lymphadenectomy was successfully performed, and postoperative pathological examination confirmed malignant teratoma of the kidney. After surgery, the patient received adjuvant chemotherapy with BEP (bleomycin, etoposide, and cisplatin) protocol. At the 6-month follow-up, pulmonary and liver metastases were discovered by CT and the patient refused any further treatment. Unfortunately, she died at 16 months postoperatively. Although primary renal malignant teratoma is extremely rare, this kind of tumor should be taken into consideration. Currently, there is no therapeutic standard consensus for this disease and the prognosis remains unclear. Early detection and surgical intervention is critical, and more research on postoperative adjuvant therapy should be performed.

KCNJ5 Mutation Contributes to Complete Clinical Success in Aldosterone-Producing Adenoma: A Study From a Single Center.

OBJECTIVE: The KCNJ5 mutation is the most frequent mutation in aldosterone-producing adenoma (APA). We aimed to illustrate the relationship between KCNJ5 and prognosis after adrenalectomy as a guide for further treatment. METHODS: Our study included 458 patients with APA. Tumor tissues were screened for somatic mutations in KCNJ5 hot-spot regions. We performed a retrospective analysis to identify correlations between KCNJ5 and clinical outcomes in 334 patients with adrenal venous sampling lateralization. RESULTS: Somatic KCNJ5 mutations were identified in 324 of 458 patients with APA (70.7%). Compared with the KCNJ5-wild type patients, patients with KCNJ5 mutations were younger, had a higher proportion of women, and had shorter durations of hypertension, lower body mass indexes (BMIs), and lower systolic blood pressure values (P < .05). During follow-up, among the 334 patients with APA with adrenal venous sampling lateralization, 320 (95.8%) presented complete biochemical success and 187 (56.0%) presented complete clinical success. One hundred eighty-seven patients with primary aldosteronism who achieved complete clinical success presented the following characteristics: age <40 years (78.7%), BMI <24 kg/m2 (71.0%), hypertension duration <5 years (78.4%), females (66.9%), and KCNJ5 mutation (65.5%). A multivariate logistic regression analysis identified BMI, hypertension duration, and KCNJ5 mutation as independent predictors of complete clinical success. CONCLUSION: The prevalence of KCNJ5 mutations was 70.7%. KCNJ5 mutation is a protective factor of complete clinical success, while BMI and hypertension duration were risk factors of incomplete clinical success.

Diagnosis and Treatment of High-risk Pregnant Women With Cushing Syndrome Caused by Adrenal Tumor.

Introduction: The occurrence of pregnancy with Cushing syndrome (CS) is rare but with high risks, posing a great challenge to the clinical diagnosis and treatment of the disease. Case Description: From Aug 2016 to Aug 2019, we admitted two pregnant women with CS caused by adrenal tumors. After multidisciplinary consultation, they underwent emergency Cesarean section because of heart failure and severe hypoxemia, and finally delivered a living baby after adjuvant therapy. Both patients underwent retroperitoneal laparoscopic adrenectomy (RLA) 2.6 and 1.5 months postpartum to have the adrenal tumors removed successfully. The postoperative pathology confirmed the adrenal tumor as adrenocortical adenoma. Partial hormone replacement therapy was initiated postoperatively and withdrawn uneventfully 1 year after RLA in both patients, and both patients have recovered well. Conclusions: It is difficult to find CS in early pregnancy, and when it is detected in late pregnancy, it often poses a great risk because it is necessary to consider the safety of both mother and fetus, which requires multidisciplinary coordination and cooperation to positively adjust the cardiopulmonary function and internal environment after Cesarean section, knowing that timely RLA to remove the adrenocortical adenoma can effectively cure CS.