Renal enhanced CT images reveal the tandem mechanism between tumor cells and immunocytes based on bulk/single-cell RNA sequencing.

Metabolic reprogramming is essential for establishing the tumor microenvironment (TME). Glutamine has been implicated in cancer metabolism, but its role in clear cell renal carcinoma (ccRCC) remains unknown. Transcriptome data of patients with ccRCC and single-cell RNA sequencing (scRNA-seq) data were obtained from The Cancer Genome Atlas (TCGA, 539 ccRCC samples and 59 normal samples) database and GSE152938 (5 ccRCC samples). Differentially expressed genes related to glutamine metabolism (GRGs) were obtained from the MSigDB database. Consensus cluster analysis distinguished metabolism-related ccRCC subtypes. LASSO-Cox regression analysis was used to construct a metabolism-related prognostic model. The ssGSEA and ESTIMATE algorithms evaluated the level of immune cell infiltration in the TME, and the immunotherapy sensitivity score was obtained from TIDE. Cell-cell communication analysis was used to observe the distribution and effects of the target genes in the cell subsets. An image genomics model was constructed using imaging feature extraction and a machine learning algorithm. Results: Fourteen GRGs were identified. Overall survival and progression-free survival rates were lower in metabolic cluster 2, compared with those in cluster 1. The matrix/ESTIMATE/immune score in C1 decreased, but tumor purity in C2 increased. Immune cells were more active in the high-risk group, in which CD8 + T cells, follicular helper T cells, Th1 cells, and Th2 cells were significantly higher than those in the low-risk group. The expression levels of immune checkpoints were also significantly different between the two groups. RIMKL mainly appeared in epithelial cells in the single-cell analysis. ARHGAP11B was sparsely distributed. The imaging genomics model proved effective in aiding with clinical decisions. Glutamine metabolism plays a crucial role in the formation of immune TMEs in ccRCC. It is effective in differentiating the risk and predicting survival in patients with ccRCC. Imaging features can be used as new biomarkers for predicting ccRCC immunotherapy.

Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells.

BACKGROUND/AIMS: Melanoma antigen A6 (MAGEA6) is a cancer-specific ubiquitin ligase of AMP-activated protein kinase (AMPK). The current study tested MAGEA6 expression and potential function in renal cell carcinoma (RCC). METHODS: MAGEA6 and AMPK expression in human RCC tissues and RCC cells were tested by Western blotting assay and qRT-PCR assay. shRNA method was applied to knockdown MAGEA6 in human RCC cells. Cell survival and proliferation were tested by MTT assay and BrdU ELISA assay, respectively. Cell apoptosis was tested by the TUNEL assay and single strand DNA ELISA assay. The 786-O xenograft in nude mouse model was established to test RCC cell growth in vivo. RESULTS: MAGEA6 is specifically expressed in RCC tissues as well as in the established (786-O and A498) and primary human RCC cells. MAGEA6 expression is correlated with AMPKα1 downregulation in RCC tissues and cells. It is not detected in normal renal tissues nor in the HK-2 renal epithelial cells. MAGEA6 knockdown by targeted-shRNA induced AMPK stabilization and activation, which led to mTOR complex 1 (mTORC1) in-activation and RCC cell death/apoptosis. AMPK inhibition, by AMPKα1 shRNA or the dominant negative AMPKα1 (T172A), almost reversed MAGEA6 knockdown-induced RCC cell apoptosis. Conversely, expression of the constitutive-active AMPKα1 (T172D) mimicked the actions by MAGEA6 shRNA. In vivo, MAGEA6 shRNA-bearing 786-O tumors grew significantly slower in nude mice than the control tumors. AMPKα1 stabilization and activation as well as mTORC1 in-activation were detected in MAGEA6 shRNA tumor tissues. CONCLUSION: MAGEA6 knockdown inhibits human RCC cells via activating AMPK signaling.

[Ningmitai Capsules relieve lower urinary tract symptoms in patients with benign prostatic hyperplasia : A short-term clinical observation].

OBJECTIVE: To observe the clinical effect and safety of the Chinese patent medicine Ningmitai Capsules (NMT) in relieving lower urinary tract symptoms (LUTS) in the patient with benign prostatic hyperplasia (BPH). METHODS: We randomly assigned 40 BPH patients to an experimental and a control group of equal number to receive oral administration of NMT at 4 capsules tid and terazosin hydrochloride tablets at 2 mg qd, respectively, both for 14 days. At 7 and 14 days after medication, we recorded and compared the International Prostate Symptoms Score (IPSS), maximum urinary flow rate (Qmax), quality of life (QoL) scores, results of urinalysis and blood routine examination, and indexes of hepatic and renal function. RESULTS: Both NMT and terazosin significantly improved the total IPSS score, the IPSS scores in the storage and voiding phases, increased Qmax and urine output, reduced post-void residual urine (PVR), and improved the QoL of the patients. The patients of the NMT group showed a better relief of incomplete bladder emptying, more improved QoL and fewer adverse reactions, while those treated with terazosin achieved a better attenuation of weak urine stream and PVR. CONCLUSIONS: NMT is safe and effective in relieving LUTS in BPH patients. Each of NMT and terazosin has its own advantages in attenuating urinary tract irritation and obstruction, but whether their combination may produce a better effect on LUTS and the specific mechanisms of NMT improving acute symptoms of BPH are yet to be further studied.

The protective effects of Lipoxin A4 during the early phase of severe acute pancreatitis in rats.

OBJECTIVE: Our aim was to investigate the protective effects of a Lipoxin A(4) analogue (LXA4) in the early phase of acute pancreatitis in rats. MATERIALS AND METHODS: Severe acute pancreatitis (SAP) was induced by injection of 5% sodium taurocholate into the pancreatic duct. Rats with SAP were treated with LXA4 (0.1 mg/kg), 10 min after the 5% sodium taurocholate injection, after which LXA4 was administrated every 8 hours, three times (LXA4 group). The sham group was only given the vehicle after operation. Plasma amylase activity, serum levels of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α) were measured at 4, 12, and 24 h after induction of SAP. The pancreatic index and histopathologic observations were evaluated and the expression of intercellular adhesion molecule-1 (ICAM-1) and NF-κB p65 in the pancreas, and the expression of ICAM-1 in the lungs were detected by immunohistochemistry. RESULTS: LXA4 treated rats had lower serum levels of TNF-α, IL-1, and IL-6 at all time points measured (p < 0.05), but significantly differed in plasma amylase activity only at 24 h as compared with the SAP group. The pancreatic index and the scores of pancreatitic histopathologic evaluations were lower in the LXA4 group as compared to the SAP group. Immunohistochemistry showed that LXA4 attenuated the expression of ICAM-1 and NF-κB p65 in the pancreas, as well as the expression of ICAM-1 in the lungs in animals with pancreatitis (p < 0.05). CONCLUSIONS: We demonstrate that LXA4 has protective effects in experimental SAP, which may be achieved by inhibiting the NF-κB signalling pathway, thereby reducing the production of proinflammatory cytokines.

[Etiology, diagnosis and management of spontaneous per renal hemorrhage].

OBJECTIVE: To investigate the etiology, diagnosis, and management of spontaneous perirenal hemorrhage (SPH). METHODS: The clinical data of 35 patients, 10 males and 12 females, aged 35.9 (12-77), with the diagnosis of SPH, without history of trauma, anticoagulant use, dialysis, and renal transplantation, were analyzed. RESULTS: The underlying disease of SPH included angiomyolipoma (18 cases), renal cell carcinoma (7 cases), kidney cyst (2 cases), renal artery aneurysm (3 cases), rupture of renal artery aneurysm accompanied with pregnancy (2 cases), renal pheochromocytoma (3 cases 2 of which accompanied with pregnancy), congenital stricture of pelvic ureter junction (1 case), and liver cancer (1 case). The most common underlying diseases were nephrogenic (96%) with angiomyolipoma ranking first (54%) followed by renal cell carcinoma (21%). The underlying diseases were diagnosed correctly in 23 cases (69%). CT helped in diagnosis of 34 cases. Surgery was performed on most of the cases. CONCLUSION: The most common causes of SPH is renal neoplasms more than 50% of which are benign. Renal artery aneurysm and pheochromocytoma tend to rupture during pregnancy. CT is the first method of choice in diagnosis.

Insulin resistance in patients with advanced prostate cancer undergoing intermittent or continuous androgen blockade.

BACKGROUND AND OBJECTIVE: Androgen blockade is the principle strategy in the treatment of advanced prostate cancer. Impaired glucose tolerance often occurs in those patients after androgen blockade. This study was to investigate the correlation of insulin resistance to intermittent androgen blockade (IAB) or continuous androgen blockade, which is also named surgical castration, in patients with advanced prostate cancer. METHODS: A total of 139 patients with advanced prostate cancer were classified into four groups according to the body mass index (BMI) and the treatment method. Group A consisted of 30 patients receiving surgical castration with BMI >or= 24 kg/m(2), group B consisted of 32 patients treated with IAB with BMI >or= kg/m(2), group C consisted of 37 patients undergoing surgical castration with BMI < 24 kg/m(2), group D consisted of 40 patients treated by IAB with BMI < 24 kg/m(2). Fasting plasma glucose (FPG) and fasting serum level of insulin (FINS) were assessed before treatment, six months and 12 months after treatment, respectively. Insulin resistance index (IRI) was also calculated. RESULTS: Six months after treatment, FINS and IRI were all increased in the four groups compared with those before treatment; FINS and IRI were significantly higher in groups B and D than in A and C (FINS: t(A:B)=7.7516, p < 0.01, t(C:D)=4.8078, p < 0.01; IRI: t(A:B) =7.3671, p < 0.01, t(C:D)=5.1005, p < 0.01). Twelve months after treatment, which was the intermittent period of the IAB method, FINS returned to the pretreatment level in group D (q=2.5255, p > 0.05), and dramatically decreased in group B compared to the value six months after treatment (q = 9.0942, p < 0.01); in contrast, FINS and IRI remained unchanged in groups A and C. CONCLUSIONS: Androgen blockade promotes insulin resistance in patients with advanced prostate cancer. Insulin resistance gradually disappears during the intermittent period of IAB.