Bisphenol A-elicited miR-146a-5p impairs murine testicular steroidogenesis through negative regulation of Mta3 signaling.

The epigenetic effects on expression of non-coding RNAs (e.g. microRNAs) of environmental toxin bisphenol A (BPA) have extended our understanding of the etiology of human reproductive disorders including hypospermatogenesis and androgen deficiency. BPA-induced miR-146a-5p is a potent regulator of endocrine and immune homeostasis, but its role in testis remain unexplored. We show here that in murine testis, miR-146a-5p was exclusively expressed in interstitial Leydig cells (LCs). This expression was significantly induced by BPA exposure. Consequently, the elevated miR-146a-5p exacerbated the deleterious effects of BPA on testicular steroidogenesis. Mechanistically, miR-146a-5p repressed the expression of Mta3, a pivotal chromatin remodeling transcription factor recently involved in controlling the steroidogenic activity, via directly targeting its 3'UTR. This repression thereafter rendered LCs more sensitive to BPA-elicited inhibitory effects. Conversely, ectopic expression of hMTA3 successfully rescued miR-146a-5p-elicited inhibitory effects on testicular steroidogenesis in BPA-challenged LCs. Taken together, the available data provide novel evidence that deregulation of testicular miR-146a-5p/Mta3 cascade mediates, at least in part, the steroidogenic dysfunction caused by BPA exposure.

Sodium vitamin C transporter 2 orchestrates lactate metabolism in mouse Sertoli cells.

Transportation of vitamin C (also called ascorbic acid (AA)), an important water-soluble antioxidant and cofactor in testis, requires glucose transporter family (GLUTs) and sodium/vitamin C cotransporter family (SVCT1 and SVCT2). There is so far scant information vis-à-vis the functional roles of SVCTs in testis, although they possess higher affinity for transportation of AA compared to GLUTs. To analyze the biological effects of SVCT2 in testis, we assessed testicular expression of SVCT2 in different experimental settings and the effect of SVCT2 ablation on spermatogenesis. Persistent expression of SVCT2 was shown in the mouse testis at different stages of postnatal development, demonstrated on day 14 of testicular development in mice consistent with the appearance of pachytene spermatocytes during the first wave of spermatogenesis. Testicular expression of SVCT2 was enriched in the cytoplasm of murine Sertoli cells (SCs). We then showed that in vivo inhibition of SVCT2 in mouse testis significantly impaired male fertility by causing oligozoospermia and asthenospermia, which mainly stemmed from a deficiency in lactate production. By generating the TM4SVCT2-/- cells and by profiling TM4SVCT2-/- cells with a constitutively activated HIF-1α mutant, we demonstrated that SVCT2 deficiency led to impaired lactate synthesis and reduced expression of Ldha mRNA in SCs. Mechanistically, ablation of SVCT2 resulted in ubiquitination and subsequent degradation of HIF-1α protein in the FSH-stimulated SCs. Collectively, our data document a novel testicular site of action of SVCT2 in the control of lactate synthesis by SCs, probably via ubiquitination-dependent regulation of HIF-1α stability.

Artificial Intelligence-Aided Diagnosis Software to Identify Highly Suspicious Pulmonary Nodules.

INTRODUCTION: To evaluate the value of artificial intelligence (AI)-assisted software in the diagnosis of lung nodules using a combination of low-dose computed tomography (LDCT) and high-resolution computed tomography (HRCT). METHOD: A total of 113 patients with pulmonary nodules were screened using LDCT. For nodules with the largest diameters, an HRCT local-target scanning program (combined scanning scheme) and a conventional-dose CT scanning scheme were also performed. Lung nodules were subjectively assessed for image signs and compared by size and malignancy rate measured by AI-assisted software. The nodules were divided into improved visibility and identical visibility groups based on differences in the number of signs identified through the two schemes. RESULTS: The nodule volume and malignancy probability for subsolid nodules significantly differed between the improved and identical visibility groups. For the combined scanning protocol, we observed significant between-group differences in subsolid nodule malignancy rates. CONCLUSION: Under the operation and decision of AI, the combined scanning scheme may be beneficial for screening high-risk populations.

Efficacy of Catheter-directed Thrombolysis on Post-burn Deep Venous Thrombosis of Lower Extremity.

OBJECTIVE: To observe the clinical effect of catheter-directed thrombolysis on deep venous thrombosis (DVT) of lower extremity after burn. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Invasive Technology Department, Binzhou City Center Hospital, China, from January 2015 to November 2017. METHODOLOGY: Eighty-two patients with lower extremity DVT after burn were selected as the study object. All patients received catheter-directed thrombolysis and the clinical efficacy was evaluated. The blood coagulation parameters including plasma prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrin original (FIB) and inflammatory response factors including interleukin (IL)-6, C-reactive protein (CRP) and D-dimer were compared before and after treatment. RESULTS: All interventional surgeries that the patients received were successful. The effective rate of catheter-directed thrombolysis was 98.78% (81 cases). After 6 days of treatment, compared with that before treatment, serum PT, APTT and TT were up-regulated (all p <0.001) and FIB was down-regulated (p <0.001). After 6 days of treatment, the levels of serum IL-6, CRP and D-dimer were lower than those before treatment (all p <0.001). No visceral hemorrhage occurred after 1 week of treatment. CONCLUSION: Catheter-directed thrombolysis of patients with lower extremity DVT after burn produces a good effect. It can improve the coagulation function and reduce the level of inflammatory response factors in patients with high safety.

Role of interleukin-10 polymorphisms and haplotypes in polycystic ovary syndrome risk.

Polycystic ovary syndrome (PCOS) is one of the most frequently encountered endocrine malfunctions. The etiology of PCOS is complex and unclear. We aimed to investigate the role of three common SNPs (rs1800896, rs1800871 and rs1800872) of IL-10 in the development of PCOS in a Chinese population. We recruited 360 patients with PCOS and 360 healthy controls in this study. SNP genotyping of IL-10 rs1800896, rs1800871 and rs1800872 was implemented in a 384-well plate format on the Sequenom MassARRAY® System (Sequenom, San Diego, USA). Individuals carrying the GG genotype of rs1800872 were associated with an increased risk of PCOS when compared with the AA genotype (OR = 3.04, 95% CI = 1.62-5.69). No linkage disequilibrium was observed among IL-10 rs1800896, rs1800871 and rs1800872. The C-T-A (OR = 1.53, 95% CI = 1.05-2.35) haplotype indicated an increased risk of PCOS, while the A-C-G (OR = 0.72, 95% CI = 0.53-0.98) showed a reduced risk of PCOS. In summary, this study firstly estimates the association between IL-10 polymorphisms and haplotype and PCOS risk in the Chinese population.

Pulmonary lymphangioleiomyomatosis--a case report.

Pulmonary lymphangioleiomyomatosis (PLAM) is a rare disease, occurs in 16-68-year-old women, especially in women of childbearing age. High-resolution computed tomography would be useful for diagnosis of PLAM. Immunohistochemistry of smooth muscle actin (SMA) and HMB-45 smooth muscle cells was positive for smooth muscle cells. Progesterone receptor and estrogen receptor in some smooth muscle cells were positive for some smooth muscle cells. HMB-45-positive diagnosis of the disease is more important.