Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway

The aryl hydrocarbon receptor (AhR) is an important immune regulator with a role in inflammatory response. However, the role of AhR in IL-10 production by inflammatory macrophages is currently unknown. In this study, we investigated LPS-induced IL-10 expression in macrophages from AhR-KO mice and AhR-overexpressing RAW264.7 cells. AhR was highly expressed after LPS stimulation through NF-κB pathway. Loss of AhR resulted in reduced IL-10 expression in LPS-induced macrophages. Moreover, the IL-10 expression was elevated in LPS-induced AhR-overexpressing RAW264.7 cells. Maximal IL-10 expression was dependent on an AhR non-genomic pathway closely related to Src and STAT3. Furthermore, AhR-associated Src activity was responsible for tyrosine phosphorylation of STAT3 and IL-10 expression by inflammatory macrophages. Adoptive transfer of AhR-expressing macrophages protected mice against LPS-induced peritonitis associated with high IL-10 production. In conclusion, we identified the AhR-Src-STAT3-IL-10 signaling pathway as a critical pathway in the immune regulation of inflammatory macrophages, It suggests that AhR may be a potential therapeutic target in immune response

Renal cell carcinoma growing into the renal pelvis and mimicking transitional cell carcinoma: A case report and literature review

Renal cell carcinoma (RCC) originated from parenchyma and the majority of malignancies originating in the renal pelvis are transitional cell carcinoma (TCC). In the present study, a rare case of RCC growing into the renal pelvis and mimicking TCC in medical imaging is reported. The preoperative differentiation between RCC and TCC is important in order to identify the type of surgical treatment required: Nephrectomy or ureteronephrectomy. The role of ureteroscopy and biopsy is emphasized in the accurate preoperative diagnosis of a renal pelvic mass. Thus, the present study provided fundamental evidence for the pathogenesis of RCC with pelvic extension and challenged the present tumor node metastasis staging system of RCC

Fast Counterfactual Inference for History-Based Reinforcement Learning

Incorporating sequence-to-sequence models into history-based Reinforcement Learning (RL) provides a general way to extend RL to partially-observable tasks. This method compresses history spaces according to the correlations between historical observations and the rewards. However, they do not adjust for the confounding correlations caused by data sampling and assign high beliefs to uninformative historical observations, leading to limited compression of history spaces. Counterfactual Inference (CI), which estimates causal effects by single-variable intervention, is a promising way to adjust for confounding. However, it is computationally infeasible to directly apply the single-variable intervention to a huge number of historical observations. This paper proposes to perform CI on observation sub-spaces instead of single observations and develop a coarse-to-fine CI algorithm, called Tree-based History Counterfactual Inference (T-HCI), to reduce the number of interventions exponentially. We show that T-HCI is computationally feasible in practice and brings significant sample efficiency gains in various challenging partially-observable tasks, including Maze, BabyAI, and robot manipulation tasks

Chronic scrotal pain caused by Mild Epididymitis: Report of a series of 44 cases

Objectives: Patients with idiopathic chronic scrotal pain are challenging to both the general practioner and urologist. In this study, we tried to recognize mild epididymitis as an underrecogniczed cause of idiopathic chronic scrotal pain. Methods: We described a consecutive series of 44 patients with idiopathic chronic scrotal pain characterized by mild scrotal pain, mild to moderate tenderness of epididymis without abnormal swelling of epididymis. We obtained a detailed history and physical examination along with routine urinalysis and Doppler ultrasound to identify the characteristics of this new clinical entity. Results: A consecutive series of 44 patients who were primarily diagnosed as "idiopathic chronic scrotal pain" came to our hospital. All had the sign of mild to moderate tenderness on the affected epididymis without epididynnis enlargement. Doppler ultrasound showed the affected epididymis with normal size and no abnormal change. We treated them with antibiotics orally along with cessation of strenuous activity and all fully recovered from scrotal pain. Conclusion: In this study, we recognized mild epididymitis as an underrecogniczed cause of idiopathic chronic scrotal pain. It was characterized by mild scrotal pain, mild to moderate tenderness of epididymis without abnormal enlargement of epididymis

Adenomatoid tumors of the testis: A report of two cases and review of the literature

Adenomatoid tumors are rare benign neoplasms that normally occur in the scrotum. The clinical symptoms and routine examinations mean that it is difficult to distinguish adenomatoid tumors from malignant intratesticular solid tumors, which may result in unnecessary orchidectomies. The present report describes two adenomatoid tumor patients treated between 2006 and 2013 at the Peking University Shenzhen Hospital who presented with an asymptomatic mass in the scrotum. Based on thorough analysis of clinical features, blood, radiological images and intra-operative findings, limited local excisions were performed, revealing adenomatoid tumors of the testis on pathological examination. The patients were followed up and exhibit no recurrence at the time of writing. The present report also summarizes the morphological and immunohistochemical features of paratesticular tumors and reviews the literature to improve understanding of these rare lesions and assist in accurate diagnosis

Investigating urachal carcinoma for more than 15 years

Urachal carcinomas are rare bladder malignances, which usually present at an advanced stage with a high risk of distant metastases and a poor prognosis. To improve understanding of this uncommon carcinoma, a retrospective review was conducted for the cases observed at Peking University Shenzhen Hospital and Peking University First Hospital. The clinical outcomes were analyzed for 17 patients with a diagnosis of urachal cancer, who were admitted to Peking University Shenzhen Hospital (Shenzhen, China) and Peking University First Hospital (Beijing, China) between 1998 and 2013. The TNM staging system was used to predict outcomes. Among the 17 study patients, there were 10 males and seven females, with a median age at diagnosis of 50 years. A total of four (23%) patients presented with lymph node or distant metastasis. The median overall survival time for all stages was 57.6 months, with five patients (38.4%) alive for more than five years following treatment. The application of the TNM staging system demonstrated a median survival time of 6.2 years for stage I/II patients, compared with a median survival of 1.8 years (log-rank, P<0.001) for patients with advanced disease (stages III and IV). In addition, no significant correlation was observed between tumor size and age, and survival. In conclusion, urachal carcinomas are usually locally advanced at presentation. Surgical excision remains the predominant choice of treatment and lymph node dissection is not required unless lymph node involvement is confirmed by preoperative examination. The current results indicated that the most significant predictor of prognosis was the tumor grade

Bizarre leiomyoma of the scrotum: A case report and review of the literature

Bizarre leiomyomas of the scrotum are rare benign tumors that are often misdiagnosed. In this study, we present a case of bizarre leiomyoma of the scrotum in a 53-year-old male. The patient presented with a painless scrotal mass that was insidious in the right side of the scrotum with no sudden increase in size. Definitive preoperative diagnosis could not be established; however, following surgical resection of the tumor, a diagnosis of bizarre leiomyoma of the scrotum was determined by pathological examination. The patient was followed up six months following resection and no problems were reported. This is the first reported case of bizarre leiomyoma of the scrotum in China. A supplementary review of previously published cases and literature is also presented

miR-886-3p upregulation in clear cell renal cell carcinoma regulates cell migration, proliferation and apoptosis by targeting PITX1

miR-886-3p has been discovered to be involved in the oncogenesis, progression and metastasis of several types of human cancer. The aim of the present study was to identify the biological function of miR-886-3p in clear cell renal cell carcinoma (ccRCC) and to determine its possible molecular mechanisms. miR-886-3p was found to be significantly upregulated in ccRCC tissues (P<0.05), in accordance with a previous sequencing result. Functional experiments revealed that forced downregulation of miR-886-3p significantly inhibited cellular migration, suppressed cell proliferation and induced cell apoptosis of renal cancer cells. Paired-like homeodomain 1 (PITX1), which has been identified as a tumor suppressor, was found to be downregulated in ccRCC tissues and identified as a target gene of miR-886-3p. Further experiments demonstrated that the protein level, and not the mRNA level, of PITX1 was significantly decreased or increased when miR-886-3p was upregulated or downregulated, respectively, indicating that miR-886-3p acted as an oncogene by directly regulating the protein expression of PITX1 at a post-transcriptional level. In conclusion, this study revealed that miR-886-3p was upregulated in ccRCC and was involved in cellular migration, proliferation and apoptosis of renal cancer cells by directly targeting the tumor suppressor gene, PITX1

microRNA-184 functions as tumor suppressor in renal cell carcinoma

microRNAs (miRNAs) are evolutionarily conserved, endogenous, small, noncoding RNA molecules of approximately 22 nucleotides in length that function as post-transcriptional gene regulators. Their aberrant expression may be involved in human diseases, including cancer. Although miRNA-184 (miR-184) has been reported in other tumors, its function in renal cell carcinoma (RCC) is still unknown. The aim of the present study was to investigate the role of miR-184 in RCC. The impacts of miR-184 on cell migration, proliferation and apoptosis were evaluated using migration scratch, 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assay. Our studies revealed that miR-184 mimic significantly inhibits cell migration, suppresses cell proliferation and induces renal cancer cell apoptosis in vitro when compared with the negative control (P<0.05). In this study, it was observed that miR-184 played a significant role as a tumor suppressor in RCC. Therefore, miR-184 may be a promising therapeutic target for renal cancer treatment in the future