Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation.

ABSTRACT: Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.

Comparison of outcomes in three surgical techniques for proximal hypospadias: staged transverse preputial island flap urethroplasty versus single-stage repairs.

To evaluate and compare the outcomes and complications of three different surgical techniques for treating primary proximal hypospadias with ventral curvature (VC) ≥30°, we retrospectively reviewed the medical records of patients who underwent primary repair of proximal hypospadias with VC ≥30° after degloving at Beijing Children's Hospital Affiliated to Capital Medical University (Beijing, China) from January 2019 to January 2021. A total of 152 patients were divided into three groups: transverse preputial island flap (TPIF) combined with Duplay, modified Koyanagi, and staged TPIF, which were performed on 55, 16, and 81 patients, respectively. A total of 39 (25.7%) patients had complications. Complications rates were similar for the TPIF combined with the Duplay group (40.0%) and modified Koyanagi group (50.0%) but lower for the staged TPIF group (11.1%; P < 0.01). The incidence of urethrocutaneous fistulas was significantly higher in TPIF combined with Duplay group (21.8%) compared to staged TPIF group (4.9%; P = 0.01). In univariate analysis, the length of the urethral defect was the single factor that could predict complications; the cutoff was 4.55 cm. More patients in the long urethral defect group than in the short one had complications (34.1% vs 15.7%, P = 0.01). These results indicate that staged TPIF produced a better outcome, whereas more patients in the TPIF combined with Duplay group presented with two or more complications.

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.

Non-Wilms' renal tumors in children: experience with 139 cases treated at a single center.

BACKGROUND: Pediatric non-Wilms renal tumors (NWRTs), which comprise a small proportion of renal tumors, are a heterogeneous group of neoplasms with variable malignant potential, mortality, and response to treatment. We performed this study to determine the clinical characteristics, management and prognosis of children with Pediatric NWRTs. METHODS: Medical records of all patients (n = 139) treated for NWRTs over a 12-year period (2008.01-2019.10) at a single center were reviewed retrospectively. RESULTS: The histopathological groups of NWRTs included malignant rhabdoid tumor of the kidney (MRTK) (n: 30, 21.6%), renal cell cancer (RCC) (n: 26,18.7%), clear cell sarcoma of the kidney (CCSK) (n: 24,17.3%), congenital mesoblastic nephroma (CMN) (n: 21,15.1%), cystic nephroma (CN) (n: 16,11.5%), metanephric tumors (n: 12, 8.6%), renal angiomyoliporma (RAML) (n: 3, 2.2%), renal primitive neuroectodermal tumor (n: 2, 1.4%), renal hemangioma (n: 2, 1.4%), inflammatory myofibroblastic tumor (n: 2, 1.4%), ossifying renal tumor of infancy (ORTI) (n: 1, 0.7%). The distribution of all malignant NWRTs, including MRTK, CCSK, RCC and PNET, according to stage was as follows: stages I (n = 26), II (n = 16), III (n = 29), and IV (n = 11). The summary table shows the treatment offered to children with NWRTs. A total of 123 children were followed up for an average of 42 months. Sixteen children were lost to follow-up. Tumor-free survival was observed in 94 children. One patient who suffered from RCC is currently receiving targeted therapy and survives with the tumor. Twenty-eight children (22.8%) died. CONCLUSIONS: Pediatric NWRTs comprise 19.1% of all renal tumors in our single center. Most NWRTs can readily be distinguished using a range of immunohistochemical markers. Molecular genetic profiling has allowed much progress in the understanding of this group of tumors, making diagnosis and classification less difficult. The mainstay treatment of malignant NWRTs, including MRTK, CCSK, RCC and PNET, is comprehensive treatment. The mainstay treatment of benign NWRTs, including RAML, CN, ORTI, CMN, metanephric tumors, and renal hemangioma, is surgical resection alone and when the tumor diameter is smaller than 7 cm and the tumor locates in one pole, NSS can be performed.

[Association of phthalate and polycyclic aromatic hydrocarbon exposure during early pregnancy with premature delivery: A cohort study].

OBJECTIVE: To explore the relationship of the exposure to phthalate esters (PAE) and polycyclic aromatic hydrocarbons (PAH) with clinical premature delivery during early pregnancy. METHODS: We conducted a baseline questionnaire survey among 821 pregnant women undergoing prenatal examination in Hubei Provincial Maternal and Child Health Care Hospital, collected their morning urine samples and followed them up to the outcomes of pregnancy. We quantitatively analyzed 10 PAE and 10 PAH metabolites in the urine samples, followed by Mann-Whitney U test, chi-square test, and logistic regression analysis. RESULTS: The detection rate of the 5 factors exposed to was >80% while that of phthalic acid monobenzyl ester (MBzP) was <50% in PAEs; that of the 5 factors exposed to was >80%, that of 3-hydroxyphene (3-OHPHE) was 86.91% while that of 4-hydroxyphene (4-OHPHE) was <50% in PAHs. Logistic regression analysis showed that the risk of premature delivery was higher in the high MBzP- than in the low MBzP-exposure group (aOR = 2.26, 95% CI: 1.17－4.39). CONCLUSION: High MBzP-exposure may be a risk factor for premature delivery.

Relationship between the honeydew of mealy bugs and the growth of Phlebopus portentosus.

BACKGROUND: Phlebopus portentosus and mealy bugs form a fungus-insect gall on the roots of host plants. The fungus and mealy bugs benefit mutually through the gall, which is the key link in the nutritional mechanism of P. portentosus. The cavity of the fungus-insect gall provides an ideal shelter for mealy bugs survival and reproduction, but how does P. portentosus benefit from this symbiotic relationship? METHODOLOGY AND RESULTS: Anatomical examination of fungus-insect galls revealed that one or more mealy bugs of different generations were living inside the galls. The mealy bug's mouthpart could penetrate through the mycelium layer of the inside of the gall and suck plant juice from the host plant root. Mealy bugs excreted honeydew inside or outside the galls. The results of both honeydew agar medium and quartz tests showed that the honeydew can attract and promote the mycelial growth of P. portentosus. A test of the relationship between the honeydew and the formation of the fungus-insect gall showed that honeydew promoted gall formation. CONCLUSIONS: All experimental results in this study show that the honeydew secreted by mealy bugs can attract and promote the mycelial growth of P. portentosus, forming a fungus-insect gall, because mealy bugs' honeydew is rich in amino acids and sugars.

Competitive ability and fitness differences between two introduced populations of the invasive whitefly Bemisia tabaci Q in China.

BACKGROUND: Our long-term field survey revealed that the Cardinium infection rate in Bemisia tabaci Q (also known as biotype Q) population was low in Shandong, China over the past few years. We hypothesize that (1) the Cardinium-infected (C+) B. tabaci Q population cannot efficiently compete with the Cardinium-uninfected (C-) B. tabaci Q population; (2) no reproductive isolation may have occurred between C+ and C-; and (3) the C- population has higher fitness than the C+ population. METHODOLOGY AND RESULTS: To reveal the differences in competitive ability and fitness between the two introduced populations (C+ and C-), competition between C+ and C- was examined over several generations. Subsequently, the reproductive isolation between C+ and C- was studied by crossing C+ with C- individuals, and the fitnesses of C+ and C- populations were compared using a two-sex life table method. Our results demonstrate that the competitive ability of the C+ whiteflies was weaker than that of C-. There is that no reproductive isolation occurred between the two populations and the C- population had higher fitness than the C+ population. CONCLUSION: The competitive ability and fitness differences of two populations may explain why C- whitefly populations have been dominant during the past few years in Shandong, China. However, the potential role Cardinium plays in whitefly should be further explored.

[Preparation of a hyaluronic acid modified bovine serum albumin nanoparticle and its anti-tumor effect].

OBJECTIVE: To prepare hyaluronic acid modified bovine serum albumin nanoparticle, investigate the modification extent, the drug entrapment property and its anti-tumor effect. METHODS: Bovine serum albumin nanoparticles were prepared by desolvation method, then use hyaluronic acid to modify the surface of bovine serum albumin nanoparticle. The decrement of reactive amino groups on the surface of bovine serum albumin nanoparticles was applied to evaluate the modification extent of hyaluronic acid. Single factor was used to study the effects of several influencing factors in preparation on the modification extent of hyaluronic acid modified bovine serum albumin nanoparticles. The influence of pH on drug entrapment ratio as well as the drug entrapment property were studied. The inhibition rate of nanoparticle on HepG2 was evaluated with MTT asasay. RESULTS: The prepared hyaluronic acid modified bovine serum albumin nanoparticle had a average particle size of 396 nm, and Zeta potential of - 19.7 mV, the deceased ratio of surface reactive amino groups was 34.28%; hyaluronic acid modified mitoxantrone bovine serum albumin nanoparticles had a property of drug load ratio 11.13%, drug entrapment ratio 94.64% and 398 nm average particle size, Zeta potential - 17.9 mV, with a distinguished delayed drug release effect. A higher inhibition rate was observed for hyaluronic acid modified bovine serum albumin nanoparticle than that of mitoxantrone solution (P < 0.05). CONCLUSION: The preparation technique is stable which could be used to prepare hyaluronic acid modified bovine serum albumin nanoparticle, and the prepared nanoparticle has a higer anti-tumor effect than that of mitoxantrone solution.