Objective:To explore the expression of transmembrane protein 9(TMEM9)as an oncogene in prostate cancer(PCa),and to examine its effect on the proliferation and invasion of PCa cells as well as on the Wnt/β-catenin signaling pathway and autophagy of PCa cells by intervening with its expression.Methods:The Cancer Genome Atlas was used for pan-cancer analysis of TMEM9 expres-sion levels in different tumors,and TMEM9 protein and messenger ribonucleic acid(mRNA)levels in clinical PCa and prostatic hyper-plasia specimens were analyzed.Real-time quantitative polymerase chain reaction and western blotting were used to analyze TMEM9 expression levels in different PCa cell lines.Cell counting,terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL),and Transwell assay were used to analyze cell proliferation,apoptosis,and PCa cell invasion,respectively.Subcutaneous tu-morigenesis in nude mice was used to analyze tumor proliferation in vivo.Western blotting was used to analyze the expression of autophagy-related pathway proteins,and transmission electron microscopy and immunofluorescence colocalization were used to deter-mine the colocalization of autophagosomes and lysosomes.Results:TMEM9 was highly expressed in PCa.The mRNA and protein ex-pression levels of TMEM9 were higher in PCa tissues than in prostatic hyperplasia tissues.The expression of TMEM9 was highest in PC3 cells(human PCa cells)(t=17.150,P<0.01).In TMEM9-knocked down PC3 cells,the proliferation(t=3.165,P<0.05)and inva-sion(F=76.620,P<0.01)significantly decreased,and apoptosis(t=13.530,P=0.010)significantly increased.After knockdown of TMEM9,the volume(F=1 699.000,P<0.01)and weight(t=9.057,P<0.01)of subcutaneous tumors in nude mice were reduced,and tu-mor growth was inhibited.TMEM9 regulated the Wnt/β-catenin signaling pathway and inhibited the AKT-mTOR signaling pathway to promote autophagy in PCa cells.Conclusion:TMEM9 inhibits the AKT-mTOR signaling pathway and promotes the proliferation and invasion of PCa cells through autophagy.

_ Objective_ To evaluate the efficacy of unilateral subtotal adrenalectomy in the treatment of bilateral adrenal solitary neoplasma causing Cushing's syndrome and to elaborate the therapeutic principle. Methods From 2007 to 2013, a total of ten patients were diagnosed with Cushing's syndrome caused by bilateral solitary adrenal neoplasma. We compared patients'clinical symptoms, hormone profiles, biochemical and metabolic parameters, and imaging data before and after the surgery. Five of them chose the optimal neoplasma based on the lateralization ratio of adrenal venous sampling result and the other 5 patients chose the optimal neoplasma based on the diameter of the mass reflected by the computed tomography result and were then operated. Results After the unilateral subtotal adrenalectomy,the24-hour urinary free cortisol decreased significantly(P<0.05)and the midnight serum cortisol level also significantly reduced(P<0. 01). Plasma adrenocorticotropic hormone level increased significantly(P<0. 01). Nine patients of them did not need contralateral adrenalectomy and one patient received contralateral adrelectomy because of the remnant of Cushingnoid symptoms. Conclusion Unilateral subtotal adrenalectomy is an effective and safe way to treat Cushing's syndrome caused by bilateral solitary neoplasma.

Background and purpose:Prostate-speciifc membrane antigen (PSMA), a cell surface protein with high expression in prostate carcinoma (PC) cells, is an attractive target for PC imaging and therapy. Small-molecule radiopharmaceuticals targeting PSMA can detect the location and extent of disease with high sensitivity and speciifcity. The aim of this study was to evaluate the value of technetium-99m-labelled small molecule against PSMA (HYNIC-Glu-Urea-A,99mTc-PSMA) for the detection of primary and metastatic prostate cancers.Methods:Twenty-four prostate cancer patients and 1 patient with benign prostate hyperplasia received whole-body scan followed by abdominopelvic SPECT/CT 2 h after intravenous injection of99mTc-PSMA. Tumor to muscle uptake ratio of99mTc-PSMA was calcu-lated using region of interest (ROI) technology. The sensitivity and specificity of99mTc-PSMA were evaluated. The relationships between positive99mTc-PSMA and prostate speciifc antigen (PSA) level and Gleason Score were analyzed. Results:Based on per patient, the sensitivity and speciifcity of99mTc-PSMA were 72.7% (16/22) and 100% (3/3), re-spectively. The level of PSA in patients with positive99mTc-PSMA imaging was signiifcantly higher than that in patients with negative99mTc-PSMA imaging [(PSA median 17.31 ng/mL, range: 2.26-3 239.0 ng/mL)vs(PSA median 0.49 ng/mL, range: 0.07-9.28 ng/mL)] (Z=-3.51,P<0.001). Among newly diagnosed patients and recurrent patients with PSA more than 2.0 nm/mL, it was apparent that99mTc-PSMA imaging was able to detect lesions with improved sensitivity of 94.1% (16/17). Gleason Scores between positive99mTc-PSMA patients and negative99mTc-PSMA patients were not significantly different (Z=-0.69,P=0.52).Conclusion:With the combination of whole-body scan and tomography, 99mTc-PSMA SPECT/CT can be an excellent and speciifc molecular imaging strategy to detect prostate cancer and its metastases.

Objective To improve the diagnosis and treatment of ACTH-independent macronodular adrenal hyperplasia(AIMAH).Methods A 51-year-old female patient with Cushing's syndrome caused by AIMAH was reported.Elevated early morning plasma cortisol levels,increased 24 h urinary free cortisol excretion,and loss of the normal circadian rhythm in cortisol secretion were presented.There was no suppression of cortisol secretion by administration of low-and high-dose overnight dexamethasone suppression test.Cardio-pulmonary function was very bad with the highest blood pressure reaching 300/120 mm Hg( 1 mm Hg=0.133 kPa).Initially,she was treated with mitotane(60 mg/d),but was not effective.After taking ketoconazole (800 mg/d)for 5 days,cardio-pulmonary function was not effectively improved with blood pressure only descending to 180/120 mm Hg.Orthopnoea appeared and Spo2fell once to 75％.The patient had to undergo right total adrenalectomy immediately.ResultsThe mass resected was 10 cm× 10 cm in size and weighted 67.5 g.Histological examination of the removed adrenal revealed nonpigmented macronodular cortical hyperplasia.The patient continued to take ketoconazole (400-800 mg/d)from the 6th day of the operation without steroid replacement therapy in that period.With normal cortisol levels( plasma cortisol at 8:00 was 18.65 μg/dl,24 h urinary free cortisol was 78.75 μmol),she left hospital after the general condition had been improved.During the following updated 10 months follow up,the indexes of her laboratory examination were maintained normal.ConclusionIndividualized therapy should be adopted for the patient with AIMAH.The medication is useful to suppress the adrenal gland cortisol production for those with progression of symptoms,very high blood pressure,hypokalemia and hypoproteinemia.Once the cardio-pulmonary function improves,the target organ should be resected as soon as possible.The supplement of cortisol is not appropriate during the perioperative period.The unilateral adrenalectomy is an effective treatment for AIMAH.

Objective To improve the diagnosis and treatment ot adrenocorticotropin-independent macornodular adrenal hyperplasia (AIMAH).Methods The clinical data of 17 cases with AIMAH from 2000 to 2011 were analyzed retrospectively,including 3 subclinical AIMAH,10 clinical AIMAH and 4 highrisk AIMAH patient,with common radiological characteristic of bilaterally enlarged adrenal glands with multiple nodules like ginger.The 3 cases of subclinical AIMAH patients presented with decreased serum ACTH,normal or slightly elevated plasma cortisol and urinary free cortisol level,no suppression following 1 mg overnight dexamethasone suppression test and absence of clinical signs of Cushing syndrome (CS).While clinical AIMAH and high-risk AIMAH presented with clinical signs of CS,elevated plasma cortisol and urinary free cortisol level,suppressed serum ACTH,loss of normal circadian rhythm in cortisol secretion and no suppression following the low-dose and high-dose overnight dexamethasone suppression test.Among the 4 cases of high-risk AIMAH,2 cases presented with osteoporosis,2 cases with hepatic dysfunction,3 cases with cardiopulmonary dysfunction,and 4 cases with severe hypertension.Three cases of subclinical AIMAH were treated with symptomatic treatment,10 cases of clinical AIMAH patients with surgical operation,4 cases of high-risk AIMAH patients with ketoconazole and surgical operation.Results Three subclinical AIMAH patients received symptomatic treatment and discharged from hospital with normal blood pressure and blood glucose.During the period of follow-up from 3 months to 3 years,endocrine results were normal.Seven clinical AIM AH patients underwent unilateral adrenal tumor resection plus ipsilateral partial adrenalectomy or total adrenalectomy.CS disappeared completely after 6 to 9 months.Two clinical AIMAH patients underwent simultaneous bilateral adrenalectomy.One case died of adrenal crisis after operation,and the other case presented with adrenal insufficiency but returned to normal after glucocorticoid replacement therapy,no Nelson's syndrome happened during the follow-up for 5 years.One clinical AIMAH patient undertook unilateral adrenalectomy twice by interval,followed by routine corticosteroid replacement therapy.Followed up for 10 years,no Nelson's syndrome happened.Four high-risk AIMAH patients received ketoconazole and then underwent right total adrenalectomy.Cortisol levels returned to normal after 1 to 2 months and during the follow-up for 1 to 3 years,the laboratory examinations maintained normal.Conclusions Different treatment methods should be adapted to different subtypes of AIMAH.For subclinical AIMAH,the principal treatment is symptomatic,and close follow-up with regular adrenal imaging and endocrine examination is required.Surgical operation should be performed when clinical symptoms of AIMAH appear.Medical management is essential for high-risk AIMAH to inhibit the production of cortisol at first.Once these patients could stand the stimulation caused by operation,the adrenal glands should be resected as soon as possible.The unilateral adrenalectomy is an effective treatment for clinical AIMAH.