Construction and evaluation of a novel prognostic risk model of aging-related genes in bladder cancer.

Background: Bladder cancer (BLCA) is the most common malignancy of the urinary system. Muscle-invasive bladder cancer (MIBC), which constitutes approximately 25% of all BLCA cases, is characterized by frequent recurrence and early onset of metastasis. Bladder cancer most commonly occurs in elderly patients and is significantly associated with aging. However, the prognostic value of age-related genes in BLCA, especially in MIBC, remains unclear. Materials and methods: Training and testing sets were obtained from The Cancer Genome Atlas BLCA project. Differentially expressed genes between BLCA and normal samples intersected with human aging-related genes. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were used to identify prognostic aging-related signatures, followed by the construction of a risk score model and nomogram. Kaplan-Meier and receiver operating characteristic analyses were conducted to assess the predictive power. An independent BLCA cohort of 165 samples was included for external validation. The CIBERSORT algorithm was used to explore the characteristics of the immune microenvironment. Results: Seven genes (IGF1, NGF, GCLM, PYCR1, EFEMP1, APOC3, and IFNB1) were identified by Cox and least absolute shrinkage and selection operator analyses. After combining the gene signature with the clinical parameters of patients with BLCA, a risk-prognosis model and nomogram were constructed and validated with the testing set. Bladder cancer cases with high 7-gene signature scores (high-risk group) and low scores (low-risk group) showed distinct prognoses. Furthermore, 7 types of immune cells were significantly altered between the low- and high-risk groups. Conclusions: Collectively, our data provide a 7-gene signature that serves as a potential biomarker for BLCA, especially MIBC. Moreover, this 7-gene signature highlights the role of the tumor immune microenvironment in prognosis and thus might be related to the response to anti-programmed cell death protein 1-based immunotherapy.

Targeting macrophage polarization as a promising therapeutic strategy for the treatment of osteoarthritis.

Osteoarthritis (OA) is a chronic osteoarthropathy characterized by the progressive degeneration of articular cartilage and synovial inflammation. Early OA clinical treatments involve intra-articular injection of glucocorticoids, oral acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), which are used for anti-inflammation and pain relief. However, long-term use of these agents will lead to inevitable side effects, even aggravate cartilage loss. At present, there are no disease-modifying OA drugs (DMOADs) yet approved by regulatory agencies. Polarization regulation of synovial macrophages is a new target for OA treatment. Inhibiting M1 polarization and promoting M2 polarization of synovial macrophages can alleviate synovial inflammation, relieve joint pain and inhibit articular cartilage degradation, which is a promising strategy for OA treatment. In this study, we describe the molecular mechanisms of macrophage polarization and its key role in the development of OA. Subsequently, we summarize the latest progress of strategies for OA treatment through macrophage reprogramming, including small molecule compounds (conventional western medicine and synthetic compounds, monomer compounds of traditional Chinese medicine), biomacromolecules, metal/metal oxides, cells, and cell derivatives, and interprets the molecular mechanisms, hoping to provide some information for DMOADs development.

Case report: Sarcomatoid urothelial carcinoma of the renal pelvis masquerading as a renal abscess.

Sarcomatoid urothelial carcinoma (SUC), a rare tumor of the urinary tract epithelium, exhibits a high degree of malignancy and therefore a poor prognosis. Due to the absence of specific clinical presentations and imaging findings, SUC of the renal pelvis masquerades as a renal abscess is frequently under-recognized or misdiagnosed as benign inflammatory disease, resulting in delayed or erroneous treatment. Here, we report a patient with SUC of the renal pelvis who presented with a renal abscess. Repeated anti-inflammatory treatment was ineffective. Unexpectedly, cancerous cells were detected in subsequent exfoliative cytology of nephrostomy drainage fluid. In accordance with this, radical surgery and postoperative chemotherapy were conducted. Fortunately, neither recurrence nor metastasis occurred during a one-year follow-up.

ICSI outcomes for infertile men with severe or complete asthenozoospermia.

BACKGROUND: Severe or complete asthenozoospermia is a rare entity that can lead to male infertility. In this study, we explored whether different extents of severe or complete asthenozoospermia could affect intracytoplasmic sperm injection (ICSI) outcomes and compared the ICSI outcomes using testicular spermatozoa with those using ejaculated spermatozoa in couples with complete asthenozoospermia. RESULTS: Ninety-seven couples with severe or complete asthenozoospermia who underwent ICSI between January 2014 and December 2018 were included. According to the sperm category used in ICSI, patients were categorized into four groups: ejaculated progressive motile sperm group (Ep-group), ejaculated non-progressive motile sperm group (En-group), ejaculated immotile sperm group (Ei-group), and testicular sperm group (TESE-group). We compared the baseline characteristics, hormone profile, semen parameters, normal fertilization, good-quality embryos on day 3, transferred embryos, and ICSI outcomes in the four groups. The clinical pregnancy rate was significantly increased in the Ep-group (65.4%, P = 0.019) and TESE-group (63.6%, P = 0.035) compared with that in the Ei-group (23.1%). The ongoing pregnancy rate in the Ei-group was significantly lower than that in the Ep-group (23.1% vs. 61.5%, P = 0.041). Moreover, the biochemical pregnancy rate, ongoing pregnancy rate, and live birth rate were much lower in the Ei-group than in the TESE-group (30.8% vs. 63.6%, 23.1% vs. 40.4% and 23.1% vs. 40.4%, respectively). CONCLUSIONS: In couples with complete asthenozoospermia, testicular spermatozoa should be preferred to ejaculated spermatozoa for obtaining a better ICSI outcome. With the appropriate selection of testicular spermatozoa, the extent of severe or complete asthenozoospermia may not affect the ICSI outcomes. Future studies with a larger sample size are warranted to validate these findings.

RéSUMé: CONTEXTE: L'asthénozoospermiesévère ou complète est une entité rare qui peut conduire à l'infertilité masculine. Dans cette étude, nous avons exploré si les différentes étendues de l'asthénozoospermie sévère ou complète pouvaient affecter les résultats de l'injection intracytoplasmique de spermatozoïdes (ICSI), et nous avons comparé les résultats de l'ICSI obtenus avec des spermatozoïdes testiculaires à ceux obtenus avec des spermatozoïdes éjaculés chez les couples atteints d'asthénozoospermie complète. RéSULTATS: Quatre-vingt-dix-sept couples atteints d'asthénozoospermie sévère ou complète qui ont eu une ICSI entre janvier 2014 et décembre 2018 ont été inclus. Selon la catégorie de spermatozoïdes utilisée dans l'ICSI, les patients ont été classés en quatre groupes : groupe de spermatozoïdes mobiles progressifs éjaculés (groupe Ep), groupe de spermatozoïdes mobiles non progressifs éjaculés (groupe En), groupe de spermatozoïdes immobiles éjaculés (groupe Ei) et groupe de spermatozoïdestesticulaires (groupe TESE). Nous avons comparé les caractéristiques de base, le profil hormonal, les paramètres du sperme, la fécondation normale, les embryons de bonne qualité au jour 3, les embryons transférés, et les résultats de l'ICSI dans les quatre groupes. Le taux de grossesse clinique était significativement augmenté dans le groupe Ep (65,4%, P = 0,019) et le groupe TESE (63,6%, P = 0,035) par rapport à celui du groupe Ei (23,1%). Le taux de grossesse en cours dans le groupe Ei était significativement inférieur à celui du groupe Ep (23,1% contre 61,5%, P = 0,041). De plus, le taux de grossesse biochimique, le taux de grossesse en cours et le taux de naissances vivantes étaient beaucoup plus faibles dans le groupe Ei que dans le groupe TESE (30,8 % vs 63,6%,23,1 % vs 40,4 % et 23,1 % vs 40,4 %, respectivement). CONCLUSIONS: Chez les couples atteints d'asthénozoospermie complète, les spermatozoïdes testiculaires devraient être préférés aux spermatozoïdes éjaculés pour obtenir un meilleur résultat en ICSI. Avec une sélection appropriée des spermatozoïdes testiculaires, l'étendue de l'asthénozoospermie sévère ou complète pourrait ne pas affecter les résultats de l'ICSI. De futures études avec des échantillons de plus grande taille sont donc justifiées pour valider ces résultats. MOTS-CLéS: Asthénozoospermie; spermatozoïdes éjaculés ; injection intracytoplasmique de spermatozoïdes (ICSI) ; infertilité masculine ; spermatozoïdes testiculaires.

Graphene oxide with in-situ grown Prussian Blue as an electrochemical probe for microRNA-122.

An electrochemical biosensor for microRNA was constructed on the basis of direct growth of electroactive Prussian Blue (PB) on graphene oxide (GO). A mercapto-modified probe DNA that is complementary to the hepatocellular carcinoma biomarker microRNA-122 was firstly anchored on a gold electrode (AuE). Then, GO (with its large surface and multiple active sites) was adsorbed on probe DNA through π-interaction. Subsequently, the PB nanoparticles were directly grown on GO via alternative dipping the electrode in solutions of FeCl3 and hexacyanoferrate(III). Upon incubation of the resulting electrode with a solution of microRNA-122, the probe DNA on the electrode interacts with microRNA-122 to form a rigid duplex. This results in the release of electroactive PB/GO from the sensing interface and a decrease in current, typically measured at 0.18 V (vs. Ag/AgCl (3 M KCl)). The sensor covers the 10 fM to 10 nM microRNA-122 concentration range and has a 1.5 fM detection limit. The method was successfully applied to the determination of microRNA-122 in real biological samples. Graphical abstract Graphene oxide with in-situ grown Prussian Blue is applied as an electrochemical probe for the analysis of microRNA-122.

Ultrasensitive impedimetric mercury(II) sensor based on thymine-Hg(II)-thymine interaction and subsequent disintegration of multiple sandwich-structured DNA chains.

An impedimetric method is described for ultrasensitive analysis of mercury(II). It is based on thymine-Hg(II)-thymine interaction which causes the disintegration of multiple-sandwich structured DNA chains. DNA strands were selected that are partially complementary to the T-rich Hg(II)-specific oligonucleotides (MSO). They were immobilized on a gold electrode via Au-S interaction. Next, the MSO and the bridging strands (BS) that can connect adjacent MSOs were alternately attached through layer-by-layer hybridization. Thus, a multiple-sandwich structured interface in created that carries numerous MSOs. This leads to a change-transfer resistance (Rct) values of the electrode-electrolyte interface at faradic electrochemical impedance spectroscopy measurements in the presence of the hexacyanoferrate(II)/(III) redox probe at 0.2 V (vs. Ag/AgCl). If Hg(II) is added to the solution, the MSOs selectively interact with Hg(II) to produce T-Hg(II)-T structures. Hence, the multiple-sandwich hybridization chains become disintegrated, and this causes a decrease in resistivity. The effect can be used to quantify Hg(II) over an analytical range that extends over four orders of magnitude (1 fM to 10 pM), and it has a 0.16 fM limit of detection under optimal conditions. Graphical abstract An electrochemical sensor for femtomolar level detection of Hg2+ is realized on the basis of thymine-Hg2+-thymine interaction which causes disintegration of multiple sandwich DNA hybridization strands.