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.

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.

Long-term survival of a patient with a large adrenal primitive neuroectodermal tumor: A case report.

BACKGROUND: Adrenal primitive neuroectodermal tumor (PNET) is an extremely rare malignant tumor with poor prognosis and of neural crest origin. Herein, we report a case of adrenal PNET and summarized its clinical and pathological characteristics on the basis of 16 patients reported recently. CASE SUMMARY: A female patient aged 25 years presented with right lumbago for 12 mo, and pre-operative computed tomography showed a huge right adrenal mass. She received tumorectomy, and post-operative pathological examination showed adrenal PNET. After surgery, she underwent adjuvant chemotherapy and was followed up 31 mo after surgery. She received brachytherapy for right paracolic and hepatic metastases. She was alive and followed up for 60 mo. In available studies, only 57.14% (4/7) and 44.44% (4/9) were positive for the expression of neuron-specific enolase and synaptophysin, respectively, although CD99 expression was found in all the patients (100%; 10/10). CONCLUSION: It is concluded that adrenal PNET is very rare and highly malignant, and histology is a golden standard in its diagnosis. Surgery and adjuvant therapy is the main treatment.

Bioactive monoterpene indole alkaloids from Nauclea officinalis.

Two new monoterpene indole alkaloids, naucleaoffines A (1) and B (2), together with six known alkaloids (3-8), were isolated from the stems and leaves of Nauclea officinalis. The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with the data reported in literature. All isolated compounds were evaluated for their anti-inflammatory activities and anti-HIV-1 activities. Compounds 1-8 exhibited significant inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro with IC50 values comparable to that of hydrocortisone. In addition, compounds 1-8 showed significant anti-HIV-1 activities with EC50 ranged from 0.06 to 2.08 µM. These findings suggest that the discoveries of these indole alkaloids with significant anti-inflammatory activities and anti-HIV-1 activities isolated from N. officinalis could be of great importance to the development of new anti-inflammatory and anti-HIV agents.

Adrenal Ganglioneuroma: Features and Outcomes of 42 Cases in a Chinese Population.

BACKGROUND: Adrenal ganglioneuromas (AGNs) are extremely rare benign neoplasms. This study is to share our experience regarding diagnostic and operative management of these tumors. METHODS: Clinical details as well as follow-up data were retrospectively analyzed in 42 primary AGN patients who received operative resection at a tertiary referral hospital in China between May 2005 and July 2016. RESULTS: The mean age of the patients at diagnosis was 35.3 years (range 13-59 years). Among the patients, 28 were asymptomatic. The mean preoperative size was 5.3 ± 2.2 cm (range 2.1-14.0 cm), and 17 cases were larger than 5 cm. All patients underwent operative resection as open adrenalectomy in 20 patients and laparoscopy in 22 patients. The mean tumor size on pathologic examination was 6.0 ± 2.6 cm (range 2.2-17.0 cm). Laparoscopic operation showed its advantages over open surgery on the postoperative duration (5.0 vs. 7.3 days, p < 0.001) and estimated blood loss (69.5 vs. 157.5 ml, p = 0.047). No patient had recurrence or metastasis during a median follow-up of 70.5 months (range 3.7-164.3 months). CONCLUSIONS: We describe the largest AGN series reported to date. The preoperative diagnosis of AGN remains difficult despite of the progression of imaging examination. After complete resection, the prognosis of AGN patients is excellent. Laparoscopic approach has its advantages in the resection of AGNs.

[Expressions of transient receptor potential A1 and related inflammatory factors in the rat model of prostatic inflammation].

OBJECTIVE: To explore the molecular mechanism of pain associated with chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) in the rat model of prostatic inflammation. METHODS: Thirty-six male SD rats were equally randomized to an experimental and a control group, the former injected with 50 µl of 3% λ-carrageenan into the ventral prostate to make the model of non-bacterial prostatic inflammation, while the latter with the same volume of sterile saline solution. At 1, 2 and 4 weeks after modeling, the prostate, L6-S1 dorsal root ganglion (DRG) and spinal cord were harvested for examination of the expressions of the nerve growth factor (NGF), transient receptor potential ankyrin 1 (TRPA1), and calcitonin-gene-related peptide (CGRP) by immunohistochemistry and Western blot. RESULTS: The expressions of NGF, TRPA1 and CGRP in the prostatic tissue were all significantly increased in the experimental group as compared with the control (P <0.05), with a gradual decrease with the prolonging of time (P <0.05). In the L6-S1 DRG and spinal cord, the expressions of NGF, TRPA1 and CGRP exhibited no significant differences between the experimental and control groups at 1 week after modeling (P >0.05) and kept at high levels in the experimental group at 2 and 4 weeks, though not significantly different from those at 1 week (P >0.05). Statistically significant differences were observed in the expressions of the three proteins in the experimental rats among different time points (P <0.05), but not between the two groups at any time point (P >0.05). CONCLUSION: The molecular mechanism of CP/CPPS can be evaluated in the rat model of prostatic inflammation established by injecting λ-carrageenan into the prostate. TRPA1 may play an important role in connecting the upstream and down-stream pathways of CP/CPPS-associated pain.

Pathologic analysis, diagnosis and treatment of adrenal myelolipoma.

With the widespread use of non-invasive imaging modalities, the incidental detection of myelolipoma has become more common. We analyze the clinical data of 4 typical cases of unilateral adrenal myelolipomas, including 1 hormonally inactive patient and 3 hormonally active cases with hyperaldosteronemia, hypercortisolism and hyperandrogenemia. Obvious differences were found in the pathological sections. To our knowledge, this is the first article discussing the etiology of adrenal myelolipoma from pathologic analyses.

Classification, diagnosis and treatment of ACTH-independent macronodular adrenal hyperplasia.

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a distinctive subtype of Cushing's syndrome (CS), with different clinical manifestations according to the level of serum cortisol. Based on clinical manifestations and serum cortisol, we divide AIMAH into three types, subclinical AIMAH, clinical AIMAH and high-risk AIMAH, with varied treatment methods being adapted to different subtypes. At the same time, we describe 3 patients who represent these subtypes of this disease, and review some cases of AIMAH which have been previously reported in the English literature. To our knowledge, this is the first article discussing classification, diagnosis and treatment of this disease and should be useful for future therapy of AIMAH.

[PSA-based screening for prostate cancer: a comparative analysis].

PSA-based screening has always been one of the controversial topics among urological researchers. In spite of its benefit in detecting early prostate cancer, PSA-based screening may not only result in widespread overdiagnosis and overtreatment of an often indolent disease, which is life-threatening in only a minority of patients, but also subject participators to such complications as erectile dysfunction and incontinence. Besides, whether PSA-based screening can reduce prostate cancer specific mortality has received considerable attention. This review offers a comparative analysis of recent studies on PSA-based screening for prostate cancer.

[Hormonal therapy for prostate cancer: methods and prognosis].

OBJECTIVE: To search for an effective hormonal therapy for delaying the progression of prostate cancer to androgen-independent prostate cancer (AIPC). METHODS: This study included 93 cases of prostate cancer confirmed by transrectal ultrasound-guided biopsy, 22 treated by bilateral orchiectomy plus bicalutamide as a continuous androgen deprivation (CAD) therapy, and the other 71 by the intermittent androgen deprivation (IAD) therapy, the latter divided into a standard IAD group (n = 29) and a modified IAD group (n = 42) to be treated by maximum androgen blockage (MAB) until the serum PSA level decreased to less than 0.2 microg/L and the medication was maintained for 3 months. Entering the intermittent period, the patients of the standard IAD group discontinued medication, while those in the modified IAD group withdrew luteinizing hormone-releasing hormone analogue (LHRH-a) but continued the use of bicalutamide. MAB was resumed in these two groups when serum PSA manifested a continuous rise and went up to 4 microg/L until prostate cancer progressed to AIPC. Comparisons were made among the CAD, standard IAD and modified IAD groups in the follow-up time, time of progression to CRPC and treatment cycles. RESULTS: The three groups of patients were well balanced in terms of demographics, baseline characteristics and follow-up time. The median times of progression to AIPC in the CAD, standard IAD and modified IAD groups were (26.50 +/- 4.15), (30.00 +/- 7.83) and (34.93 +/- 5.08) months, respectively, with statistically significant differences between the modified IAD group and the CAD (P = 0.001) and standard IAD (P = 0.032), but not between the latter two groups (P = 0.143). Kaplan-Meier survival curves showed a significantly longer median time of progression to AIPC in the modified than in the standard IAD group (P = 0.01). The mean cycle length was (16.13 +/- 3.33) months for the standard IAD group and (19.58 +/- 4.30) months for the modified IAD group, and the time off treatment of the first cycle was (9.6 +/- 3.2) months in the former and (14.2 +/- 3.7) months in the latter, with significant difference between the two groups (P = 0.001). CONCLUSION: Compared with CAD and standard IAD, modified IAD therapy can significantly prolong the time of progression to AIPC in patients with prostate cancer.

[Compound ciprofloxacin suppository combined with ningbitai and yunnan baiyao for histological prostatitis with PSA elevation].

OBJECTIVE: To explore the efficacy of compound ciprofloxacin suppository (CCS) combined with Ningbitai (NBT) and Yunnan Baiyao (YB) capsules in the treatment of histological prostatitis with elevated levels of PSA. METHODS: This study included 150 cases of type IIIA histological prostatitis, with PSA levels ranging from 4 to 50 microg/L. After 1 month's treatment with oral Levofloxacin tablets at 0.5 g qd, the PSA levels remained high in 86 patients. Prostate cancer was excluded by transrectal ultrasound-guided prostatic biopsy, and histological prostatitis was confirmed in 65 patients, who were assigned to an experimental group (n=45) and a control group (n=20) to receive CCS combined with NBT and YB capsules and CCS with NBT only, respectively, both for 4 weeks. We determined the PSA levels, obtained NIH-CPSI scores before and after medication, and compared them between the two groups. RESULTS: The two groups were well balanced in demographics and baseline characteristics. After treatment, both showed significant differences in the PSA level, PSA density (PSAD) and CPSI scores from the baseline (P<0.05), and there were also statistically significant differences between the two groups in the changes of the PSA level and CPSI scores after medication (P = 0.029 and 0.001). CONCLUSION: Compound ciprofloxacin suppository combined with Ningbitai and Yunnan Baiyao capsules can significantly decrease the level of serum PSA and relieve related symptoms in III A histological prostatitis with PSA elevation, and Yunnan Baiyao capsules can significantly enhance the therapeutic effect.

Multi-targeted tyrosine kinase inhibitor sunitinib: a novel strategy for sporadic malignant pheochromocytoma.

Sporadic malignant pheochromocytoma, a rare disease with poor prognosis, is always difficult to treat due in part to lack of effective agents. We presented three patients with advanced malignant pheochromocytoma treated by sunitinib, which indicates that sunitinib is an effective agent for this malignancy.

Adrenal myelolipoma associated with hyperandrogenemia.

Adrenal myelolipoma associated with hyperandrogenemia is extremely rare. We present such a case here. The patient was a 34-year-old Chinese woman with a history of growth retardation, virilization and lumbago. Adrenal imaging showed a circular soft tissue mass in the right adrenal gland. Endocrine examinations showed increased levels of plasma testosterone and dehydroepiandrosterone sulfate, significantly lower levels of follicle-stimulating hormone and luteinizing hormone, with other biochemical parameters being basically normal. After a histopathological study confirming the mass to be an adrenal myelolipoma, the patient was managed with a right adrenalectomy and then recovered. A search of the English and Japanese language literature suggests this is the first detailed and documented case of adrenal myelolipoma associated with hyperandrogenemia.

Retroperitoneal adrenal-sparing surgery for the treatment of Cushing's syndrome caused by adrenocortical adenoma: 8-year experience with 87 patients.

BACKGROUND: The objective of this study was to present our 8-year experience with partial adrenalectomy via the retroperitoneal approach for the treatment of Cushing's adenoma. METHODS: A total of 93 patients who underwent adrenal surgery for Cushing's adenoma from March 2003 to December 2010 were enrolled in this study. Preoperative, intraoperative, and postoperative variables were reviewed from the database. Student's t test was used to analyze the continuous data, and the χ(2) test was used to analyze the categoric data. A value of p < 0.05 was considered statistically significant. RESULTS: Adrenal-sparing surgery was performed in 87 cases (31 by open surgery, 56 by retroperitoneal laparoscopy). Six patients underwent open/laparoscopic total adrenalectomy because of recurrent disease or a large size. The cure rate in our series was 97.8%. Hypertension resolved in 34 of 64 patients (53.1%), diabetes in 7 of 27 patients (25.9%) and obesity in 28 of 48 patients (58.3%). One patient died during the postoperative period. The intraoperative complication rate for the open surgery group was significantly higher than that for the retroperitoneal laparoscopy group (9.1 vs. 1.7%). CONCLUSIONS: The retroperitoneal approach is reliable and safe for treating Cushing's syndrome. The laparoscopic technique can decrease the prevalence of intraoperative complications. Retroperitoneal laparoscopic partial adrenalectomy can be performed with extremely low morbidity and achieves an excellent outcome, although death may occur during the postoperative period in high-risk patients. Postoperative management plays an important role in the surgical treatment of Cushing's syndrome.

Selective α1-adrenoceptor antagonist (controlled release tablets) in preoperative management of pheochromocytoma.

The objective of this article is to evaluate the efficacy of Doxazosin Mesylate Controlled Release Tablets for preoperative treatment of patients with pheochromocytoma. Between 2003 and 2008, 67 patients with confirmed diagnoses of pheochromocytoma were enrolled in this study. According to the drug used in preoperative management, patients were divided into two groups: Doxazosin Mesylate pretreatment group (n=36) and Phenoxybenzamine pretreatment group (n=31). Surgery was performed only in patients who met the optimal preoperative condition. The hematocrit decreased significantly (P<0.001) after antiadrenergic therapy in patients pretreated with phenoxybenzamine or doxazosin. There was no significant difference between the fluid intakes during operation in both groups. The systolic arterial pressures both before and after induction of anesthesia were all significantly higher in the doxazosin patients than in the phenoxybenzamine group (P<0.05). After tumor removed, the lowest systolic arterial pressure was significantly higher in doxazosin group than in phenoxybenzamine group (P<0.05). The fluctuation of systolic arterial pressure during operation was more stable in doxazosin group than in phenoxybenzamine group (P<0.05). Doxazosin mesylate controlled release tablet was as effective as phenoxybenzamine in preoperative volume expansion. Although phenoxybenzamine provided better arterial pressure control, patients pretreated with DOX experienced more stable perioperative hemodynamic changes, shorter preoperative management periods and more simple medication.

[Surgical treatment of 486 cases of adrenal gland diseases: a retrospective study].

OBJECTIVE: To evaluate the roles of laparoscopic adrenalectomy (LA) and open adrenalectomy (GA) for treatment of adrenal gland diseases. METHODS: The data of 486 patients with adrenal gland diseases was analyzed retrospectively during 5 years. A total of 478 patients received surgical treatments including 318 GAs and 160 LAs. The operation time, bleeding volume during operation, intestine function recovery time, pain postoperatively, hospital stay time postoperatively and postoperative complications in group GA and group LA respectively were compared. RESULTS: All cases in group GA were successful. A total of 154 cases in group LA were successful, and 6 cases were converted to open surgery. In group LA, there were 9 cases whose tumor diameter exceeded 6 cm. There were 3 malignant cases in group LA, and no recurrence and metastasis were observed during 3-20 months follow-up. The average operation time was (112 +/- 16) mmn and (69 +/- 10) min in group GA and LA respectively. The average bleeding volume during operation was (286 +/- 23) ml, (56 +/- 10) ml in group GA and LA respectively. The average intestine function recovery time was (66 +/- 7) h, (24 +/- 7) h in group GA and LA respectively. The average frequency of treatment of pain was 1.9 +/- 0.4 and 0.5 +/- 0.1 in group GA and LA respectively. The average hospital stay time postoperatively was (10.3 +/- 1.1) d and (7.2 +/- 0.7) d in group GA and LA respectively. The rate of postoperative complications was 40.3% and 7.5% in group GA and LA respectively. All differences were significant (P = 0.023, 0.007, 0.039, 0.003, 0.029 and 0.001). CONCLUSIONS: LA has the added benefit of shorter convalescent times, improving patients satisfaction and less associated complications, as it has proved to be as effective as OA.

LOH on chromosome 11q, but not SDHD and Men1 mutations was frequently detectable in Chinese patients with pheochromocytoma and paraganglioma.

Recently, the succinate dehydrogenase subunit D (SDHD) gene has been reported as one of the major susceptibility genes for pheochromocytoma (PCC) and paraganglioma (PGL). In addition, loss of heterozygosity (LOH) on chromosome 11, mainly in 11q23 and 11q13, is observed frequently in PGL. Based on the fact that mutation frequency of the SDHD gene is less than that of allelic loss at chromosome11q, where the SDHD gene is located, this region may contain other candidate tumor-suppressor genes involved in pathogenesis of PCC/PGL. The tumor-suppressor gene Men1 located in 11q13 is responsible for multiple endocrine neoplasia type 1 (Men1). However, the involvement of the Men1 gene in tumorigenesis of sporadic PCC/PGL is yet to be determined. To understand the roles of the two tumor-suppressor genes and LOH on chromosome 11q in Chinese patients with sporadic PCC or PGL, we performed mutation detection of the SDHD and Men1 genes in tumors from 35 Chinese patients with PCC/PGL; we also did LOH analysis at chromosome 11q for 25 patients out of the 35. No mutation was found in all of 35 patients. However, LOH was detected at one or more loci in 11 of the 25 (44%) tumor samples. The highest frequency of LOH occurred at D11S2006 (41%). Our results suggested that mutation in SDHD or Men1 gene was not found in Chinese patients with sporadic PCC/PGL. However the loss of chromosome 11q might be critical in development of PCC or PGL.

[Primary pigmented nodular adrenocortical disease report of 5 cases].

OBJECTIVE: To study the pathology, diagnostic and therapeutic method of primary pigmented nodular adrenocortical disease (PPNAD). METHODS: The data of 5 cases of PPNAD were analyzed retrospectively. Among the 5 cases, 2 were male and 3 were female. The range of age was from 12 to 53 years. All the 5 cases had symptoms of Cushing syndrome. The diagnose depended on the results of endocrine exams, ultrasound, CT, MR and pathological reports. All patients received operation of unilateral adrenalectomy. The therapeutic effects were determined by post-operative results, which concluded clinical symptoms and endocrine exams. RESULTS: The follow-up time was from 4 months to 3 years. All patients' symptoms of Cushing syndrome were relieved in 6 months after operation. The endocrine exam was normal in one case and obvious improved in the other four cases. Up to now, one patient drop out of the follow-up, the other 4 cases had no evidence of recurrence. CONCLUSION: PPNAD is a rare type of Cushing syndrome. Diagnose depends on endocrine exams and pathological results. Operation is the effective method for the disease.

[A long-term follow-up study of deep penile vein resection patients].

OBJECTIVE: To study the five-year postoperative effect of the ligation and resection of the deep penile vein for the patient of erectile dysfunction (ED) caused by penile venous leakage. METHODS: Sixteen ED patients received deep penile vein ligation and resection. Observations of the penile erection had been recorded for 5 years after surgery. RESULTS: Eight cases demonstrated erectile hypofunction after 18 months postoperatively and total ED after 21-30 months of which 6 were improved by chemotherapy, and 2 showed no improvement. Seven cases remained normal and 1 case get out of touch at the 24th month postoperatively. CONCLUSIONS: The ligation and resection of the deep penile vein can be considered as an easy and effective method to treat patients of ED caused by penile venous leakage.