Bioinformatics analysis identifies potential hub genes and crucial pathways in the pathogenesis of asthenozoospermia.

BACKGROUND: Asthenozoospermia is a troublesome disease experienced by men in their reproductive years, but its exact etiology remains unclear. To address this problem, this study aims to identify the hub genes and crucial pathways in asthenozoospermia. METHODS: We screened two Gene Expression Omnibus (GEO) datasets (GSE92578 and GSE22331) to extract the differentially expressed genes (DEGs) between normozoospermic and asthenozoospermic men using the "Limma" package. Gene enrichment analyses of the DEGs were conducted using the "clusterProfiler" R package. The protein-protein interaction (PPI) network was then established using the STRING database. A miRNA-transcription factor-gene network was constructed based on the predicted results of hub genes using the RegNetwork database. The expression of four hub genes in asthenozoospermia and normal samples were verified using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting. RESULTS: We identified 271 DEGs, which included 218 upregulated and 53 downregulated in two asthenozoospermia datasets. These DEGs were observed to be markedly enriched in pathways with cell growth and embryonic organ development, phospholipase D signaling pathway, cGMP-PKG signaling pathway, and Wnt signaling pathway. The most significant genes were identified, including COPS7A, CUL3, KLHL7, NEDD4. We then constructed regulatory networks of these genes, miRNAs, and transcription factors. Finally, we found that the COPS7A was significantly upregulated in patients with asthenozoospermia, but CUL3, KLHL7 and NEDD4 were significantly downregulated compared with normal samples. CONCLUSION: We applied bioinformatics methods to analyze the DEGs of asthenozoospermia based on the GEO database and identified the novel crucial genes and pathways in this disease. Our findings may provide novel insights into asthenozoospermia and identify new clues for the potential treatment of this disease.

A patient with 47, XYY mosaic karyotype and congenital absence of bilateral vas deferens: a case report and literature review.

BACKGROUND: The incidence of 47, XYY syndrome in live-born male infants is 1/1000. Due to its variable clinical symptoms, the diagnosis is easy to miss. The incidence of congenital bilateral absence of the vas deferens (CBAVD) in infertile men is 1-2%. The main cause is the mutation of CFTR and ADGAG2 genes. CASE PRESENTATION: The patient was a 33-year-old man who visited a doctor 5 years ago due to infertility. The investigation revealed that the patient's secondary sexual characteristics, testicular, and penis development were normal, and there was no gynecomastia, but the bilateral vas deferens and epididymis were not palpable. Transrectal ultrasound showed that the left seminal vesicle was missing, and the right seminal vesicle was atrophied. No abnormality was observed in Y chromosome microdeletion. Karyotype analysis indicated that the patient was 46, XY/47, XYY mosaic. Genetic testing found heterozygous mutations at two sites of CFTR (c263T > G and c2249C > T). CONCLUSIONS: Herein, we report the rare case of a male patient with clinical manifestations of infertility, chromosome 46, XY/47, XXY mosaic type, simultaneously manifested as the absence of bilateral vas deferens. Two pathogenic heterozygous CFTR gene mutations were found. Given the low genetic risk of the disease, we recommend that patients undergo intracytoplasmic sperm injection (ICSI) for fertility assessment.

Benzidine promotes the stemness of bladder cancer stem cells via activation of the Sonic hedgehog pathway.

Substantial evidence suggests that cancer stem cells (CSCs) are the main cause of the initiation, progression and recurrence of tumors. Benzidine has been identified as a risk factor for bladder cancer. The aim of the present study was to investigate the effects of benzidine on bladder CSCs (BCSCs) and the possible mechanism underlying its action. The bladder cancer cell lines UM-UC-3 and EJ were maintained in serum-free medium and cells forming three-dimensional spheres were characterized as BCSCs. The sphere-forming cells were exposed to different concentrations of benzidine and vismodegib, and western blotting was performed to evaluate the expression of markers associated with CSCs and the Sonic hedgehog (SHH) signaling pathway. Flow cytometry was used to detect the distribution of cells in different phases of the cell cycle, and immunofluorescence staining was used to detect the protein expression of CD44. The results revealed that the levels of BCSC markers, namely CD133, CD44, aldehyde dehydrogenase 1-A1, Nanog and octamer-binding transcription factor-4, in the cell spheres were markedly elevated compared with those in cells cultured in serum-supplemented medium. Furthermore, benzidine increased the expression of BCSC markers and promoted the sphere-forming ability of the cells. In addition, it was observed that benzidine activated the SHH pathway, while inhibition of the Shh pathway using vismodegib diminished the promoting effects of benzidine on BCSCs. The findings of the present study indicate that benzidine promoted the stemness of BCSCs via activation of the SHH pathway, which may support further exploration of the molecular basis of the association between benzidine exposure and bladder oncogenesis.

Pleomorphic rhabdomyosarcoma of the spermatic cord and a secondary hydrocele testis: A case report.

BACKGROUND: Pleomorphic rhabdomyosarcoma (RMS) of the spermatic cord is a group of rare neoplasms, and a secondary hydrocele testis occasionally occurs. The misdiagnosis of paratesticular mass may lead to a therapeutic delay. CASE SUMMARY: A 79-year-old man presented to our clinic complaining of a 1-mo history of painless scrotal swelling. Physical examination revealed approximately a 15 cm × 10 cm × 5 cm inguinal mass with limited mobility. Contrast-enhanced magnetic resonance imaging showed a hydrocele testis, several enlarged inguinal lymph nodes, and a heterogeneously enhanced lesion with a relatively well-defined margin in the left inguinal region. Due to the imaging findings, he was diagnosed with pleomorphic RMS and received a wide resection of the mass, an inguinal incision with a high section of the left spermatic cord, and a left radical orchiectomy. He experienced local relapse 1 mo postoperatively and received radiotherapy and anlotinib hydrochloride-based immunotherapy as adjuvant therapy. The patient died 3 mo after the surgery. CONCLUSION: The optimal interventions for advanced-stage pleomorphic RMS patients should be investigated by more preclinical studies and clinical trials. Physicians need to be aware of the occurrence of pleomorphic RMS in unusual locations, especially when accompanied by a hydrocele testis.

Giant adrenal germ cell tumour in a 59-year-old woman.

Adrenal germ cell tumour is very rare. We report a case of a 59-year-old woman who presented with right flank discomfort. The laboratory examinations were normal and the chest computed tomography (CT) showed right pleural effusion. The abdominal CT scan revealed a large mass on the right adrenal gland. The patient underwent an adrenalectomy. Histopathologic examination and immunohistochemical findings were consistent with mixed germ cell tumour. Three months later following the operation, the patient was admitted to our hospital again with chest tightness and shortness of breath. The chest CT showed right pleural effusion recurrence and enlargement of mediastinal lymph nodes and right hilar lymph nodes. The patient had right supraclavicular lymphadenectasis on physical examination. Fine needle aspiration cytology from the supraclavicular lymph nodes showed groups of malignant tumour cells. The patient died within 6 months postoperatively. In this case, the lymph node pathway played an important role in the metastatic procedure.

Metastasis to the proximal ureter from prostatic adenocarcinoma: A rare metastatic pattern.

Prostate cancer is one of the most common male malignancies, but it rarely metastasizes to the proximal ureter. We report a case of a 76-year-old man who presented with flank pain and lower urinary tract symptoms. Abdominal computed tomography scan revealed multiple filling defects at the middle of the left ureter, enlarged retroperitoneal lymph nodes, and probable psoas invasion. The patient underwent nephroureterectomy with excision of a cuff of bladder, and was found to have an adhesion between the middle part of left ureter and psoas intraoperatively. The pathological examination displayed positive immunohistochemical staining with prostate-specific antigen and prostate acid phostate, supporting the diagnosis of metastatic ureteral tumour from prostate cancer. In this case, periureteral soft tissue and ureteral muscular layer were infiltrated by metastatic tumour, whereas the mucosa was spared. The periureteral lymphatic pathway played an important role in the metastatic procedure of prostate cancer to the proximal ureter.