Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis.

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.

[The new progress and significance of new ultrasound technology in the diagnosis of azoospermia].

The diagnosis and treatment of azoospermia rely heavily on auxiliary ex-amination technology. Compared with CT and MRI, ultrasound has more practical value in the diagnosis of azoospermia.Currently, the main ultrasonic technologies are contrast-enhanced ultrasound, real-time ultrasound elastography and ultrasound tar-geted puncture. This article aims to summarize and prospect the application of new ultrasound technology in azoospermia.Real-time ultrasound elastography is widely used in breast diseases and is expected to play a greater role in azoospermia. Ultra-sound targeted puncture can greatly reduce the damage of testicular spermatogenic function, but its application is still not widely used.The combined application of new technologies can make up for their respective shortcomings and improve the accuracy of azoospermia diagnosis.Therefore, further research on new ultrasound technology in the diagnosis of azoospermia will play a greater role.

Risk factors for peripheral venous catheter failure: A prospective cohort study of 5345 patients.

PURPOSE: The objective of this study was to determine the independent risk factors associated with peripheral venous catheter (PVC) failure and develop a model that can predict PVC failure. METHODS: This prospective, multicenter cohort study was carried out in nine tertiary hospitals in Suzhou, China between December 2017 and February 2018. Adult patients undergoing first-time insertion of a PVC were observed from catheter insertion to removal. Logistic regression was used to identify the independent risk factors predicting PVC failure. RESULTS: This study included 5345 patients. The PVC failure rate was 54.05% (n = 2889/5345), and the most common causes of PVC failure were phlebitis (16.3%) and infiltration/extravasation (13.8%). On multivariate analysis, age (45-59 years: OR, 1.295; 95% CI, 1.074-1.561; 60-74 years: OR, 1.375; 95% CI, 1.143-1.654; ⩾75 years: OR, 1.676; 95% CI, 1.355-2.073); department (surgery OR, 1.229; 95% CI, 1.062-1.423; emergency internal/surgical ward OR, 1.451; 95% CI, 1.082-1.945); history of venous puncture in the last week (OR, 1.298, 95% CI 1.130-1.491); insertion site, number of puncture attempts, irritant fluid infusion, daily infusion time, daily infusion volume, and type of sealing liquid were independent predictors of PVC failure. Receiver operating characteristic curve analysis indicated that a logistic regression model constructed using these variables had moderate accuracy for the prediction of PVC failure (area under the curve, 0.781). The Hosmer-Lemeshow goodness of fit test demonstrated that the model was correctly specified (χ2 = 2.514, p = 0.961). CONCLUSION: This study should raise awareness among healthcare providers of the risk factors for PVC failure. We recommend that healthcare providers use vascular access device selection tools to select a clinically appropriate device and for the timely detection of complications, and have a list of drugs classified as irritants or vesicants so they can monitor patients receiving fluid infusions containing these drugs more frequently.

Prokineticin 2 overexpression induces spermatocyte apoptosis in varicocele in rats.

Varicocele is one of the most important causes of male infertility, as this condition leads to a decline in sperm quality. It is generally believed that the presence of varicocele induces an increase in reactive oxygen species levels, leading to oxidative stress and sperm apoptosis; however, the specific pathogenic mechanisms affecting spermatogenesis remain elusive. Prokineticin 2 (PK2), a secretory protein, is associated with multiple biological processes, including cell migration, proliferation, and apoptosis. In the testis, PK2 is expressed in spermatocytes under normal physiological conditions. To investigate the role of PK2 in varicocele, a rat varicocele model was established to locate and quantify the expression of PK2 and its receptor, prokineticin receptor 1 (PKR1), by immunohistochemistry and quantitative real-time PCR assays (qPCR). Moreover, H2O2 was applied to mimic the oxidative stress state of varicocele through coculturing with a spermatocyte-derived cell line (GC-2) in vitro, and the apoptosis rate was detected by flow cytometry. Here, we illustrated that the expression levels of PK2 and PKR1 were upregulated in the spermatocytes of the rat model. Administration of H2O2 stimulated the overexpression of PK2 in GC-2. Transfection of recombinant pCMV-HA-PK2 into GC-2 cells promoted apoptosis by upregulating cleaved-caspase-3, caspase-8, and B cell lymphoma 2-associated X; downregulating B cell lymphoma 2; and promoting the accumulation of intracellular calcium. Overall, we revealed that the varicocele-induced oxidative stress stimulated the overexpression of PK2, leading to apoptosis of spermatocytes. Our study provides new insight into the mechanisms underlying oxidative stress-associated male infertility and suggests a novel therapeutic target for male infertility.

The deficient cleavage of M protein-bound IgG by IdeS: insight into the escape of Streptococcus pyogenes from antibody-mediated immunity.

IdeS (IgG-degrading enzyme of Streptococcus pyogenes) is a virulence factor for S. pyogenes, group A Streptococcus (GAS). IdeS is believed to allow GAS to evade antibody-mediated phagocytosis by cleaving IgG at the lower hinge region. Human immunoglobulins bind to the GAS surface by two mechanisms: Specific antibodies attach at the Fab region to their specific antigens on the bacterial surface. Immunoglobulins can also attach nonspecifically at the Fc region to streptococcal M and M-like proteins. This phenomenon is believed to form the host-like coat and to block the recognition of Fc region by Fc receptor on phagocytes and antibody-dependent cell-mediated cytotoxicity. It is not known whether IdeS preferentially cleaves IgG attached at the Fab or Fc regions. To explore this issue, we used Sepharose beads coated with protein A or L or M protein as surrogate markers for specific (Fab) and nonspecific (Fc) binding sites. We found that IdeS cleaved Fab-bound IgG as rapidly as soluble IgG. In contrast, Fc-bound IgG was cleaved about 4 fold less than soluble IgG. In a competitive binding assay, we found that M protein had a greater affinity than IdeS to attach to the Fc region of human IgG. Thus, IdeS exhibited preferential IgG endopeptidase activity for Fab-bound IgG while allowing the non-specific binding of IgG to remain attached to M protein. We propose that this preferential enzymatic activity accounts for the ability of GAS to resist immunoglobulin-mediated phagocytosis and cytotoxicity.

Changing epidemiology of Streptococcus pyogenes emm types and associated invasive and noninvasive infections in Southern Taiwan.

A total of 242 isolates were recovered from 76 patients with invasive diseases, 89 with scarlet fever, and 77 with pharyngitis. The most frequent emm types were types 12 (43.4%), 4 (18.2%), and 1 (16.9%). emm12 reemerged in 2005 and peaked in 2007. emm11 was recovered only from patients with invasive disease.