Non-invasive evaluation of testicular torsion using ultrasound shear wave elastography: an experimental study.

PURPOSE: The goal of this study was to examine changes in testicular stiffness at various intervals after the induction of testicular torsion, as well as to assess the predictive value of testicular stiffness for testicular spermatogenesis after torsion. METHODS: Sixty healthy male rabbits were randomly assigned to one of three groups: complete testicular torsion, incomplete testicular torsion, or control. All rabbits underwent preoperative and postoperative scrotal ultrasonography, including shear wave elastography (SWE), at predetermined intervals. Changes in SWE values were analyzed and compared using repeatedmeasures analysis of variance. To assess the diagnostic performance of SWE in determining the degree of spermatogenic function impairment, the areas under the receiver operating characteristic curves (AUCs) were calculated. RESULTS: SWE measurements in both central and peripheral zones of the testicular parenchyma affected by torsion demonstrated significant negative correlations with spermatogenesis, with coefficients of r=-0.759 (P<0.001) and r=-0.696 (P<0.001), respectively. The AUCs of SWE measurements in the central or peripheral zones of the torsed testicular parenchyma were 0.886 (sensitivity, 83.3%; specificity, 100%) and 0.824 (sensitivity, 83.3%; specificity, 73.3%) for distinguishing between hypospermatogenesis and spermatogenic arrest, respectively (P=0.451, DeLong test). CONCLUSION: Variations in the stiffness of both central and peripheral regions of the testicular parenchyma correlate with the extent and duration of torsion, exhibiting a specific pattern. The "stiff ring sign" is the characteristic SWE finding associated with testicular torsion. SWE appears to aid in the non-invasive determination of the extent of spermatogenic damage in torsed testes.

Upregulated miR-322-5p regulates cell cycle and promotes cell proliferation and apoptosis by directly targeting Wee1 in mice liver injury.

Liver injury from any number of causes (e.g. chemical material, drugs and diet, viral infection) is a global health problem, and its mechanism is not clearly understood. MicroRNAs (miRNAs) expression profiling is gaining popularity because miRNAs, as key regulators in gene expression networks, can influence many biological processes and have also shown promise as biomarkers for disease. Previous studies reported the regulation effects of miRNAs in liver injury, whereas function and molecular mechanisms of miR-322-5p were still unclear. Therefore, our study focused on the biological role of miR-322-5p in carbon tetrachloride (CCl4)-induced liver injury proliferation, apoptosis, and cell cycle. A mouse model of CCl4-induced liver injury was established, and the transcriptomes and miRNAs transcriptomes of 2d and 5d liver tissues after injury were sequenced. The expression of miR-322-5p and the cell cycle genes were detected in liver tissues and Hepa1-6 cell line by miRNA RT-PCR, qRT-PCR. The effects of miR-322-5p on liver cell proliferation, cell cycle and apoptosis were evaluated using MTS assays and flow cytometry analysis. The relationship between miR-322-5p and Wee1 was predicted and confirmed by bioinformatics analysis and a dual luciferase reporter assay. Functional experiments, including an MTS assay and flow cytometric analysis, were performed to study the effects of Wee1. MiR-322-5p was upregulated in injury liver tissues, and downregulated miR-322-5p was proved to inhibit proliferation, apoptosis and arrest cell cycle at G2/M in vitro. The dual-luciferase reporter assay results indicated that miR-322-5p has a binding site at position 285 in the Wee1 3´UTR. The effects of miR-322-5p in proliferation and cell cycle regulation can be abolished by Wee1 through rescue experiments. By directly targeting Wee1 influenced the expression of several cell cycle factors, including Cyclin dependent kinase 1 (Cdk1), cyclin B1 (Ccnb1) and Cell division cyclin 25C (Cdc25C). MiR-322-5p may function as a suppressive factor by negatively controlling Wee1, thus, highlighting the potential role of miR-322-5p as a therapeutic target for liver injury.Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GSH: Glutathione, γ-glutamyl cysteinel + glycine; CCl4: Carbon tetrachloride; HE: Haematoxylin and eosin; KEGG: Kyoto Encyclopedia of Genes and Genomes.

Traditional Mongolian medicine (HHQG) attenuates CCl4-induced acute liver injury through inhibiting monocyte/macrophage infiltration via the p-P38/p-JNK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Honghua Qinggan 13 Flavor Pills (HHQG), whose Mongolian name is Guri Gumu-13, is a traditional Mongolian medicine, that was stated in the "Diagnosis and Treatment of Ming Medical Code". The HHQG has been included in the Mongolian Medicine Division of the Ministry of Health Drug Standards (1998 edition). Based on our clinical expertise, HHQG demonstrated satisfactory therapeutic effects in hepatitis and liver failure. However, the pharmacological effects and potential mechanisms of HHQG have not been investigated. AIM OF THE STUDY: In this study, we combined network pharmacology, transcriptomics, and molecular biology to detect the underlying mechanism for the effect of HHQG on acute liver injury in mice. MATERIALS AND METHODS: Network pharmacology was used to explore the pathways involved in the protective effect HHQG in acute liver injury. This effect was further verified by injecting carbon tetrachloride (CCl4; 10 mL/kg, i.p.) to induce acute liver injury in mice. Serum markers of liver injury, morphology, histology, and monocyte/macrophage infiltration in the liver tissue were investigated. Transcriptomics further defined the HHQG targets. Transwell analysis was performed to confirm that HHQG inhibited monocyte/macrophage RAW.264.7 infiltration. qPCR and Western blot were performed to explore the mechanism of action of HHQG. RESULTS: Network pharmacology showed that HHQG exerted anti-oxidative and anti-inflammatory effects and promoted metabolic effects against acute liver injury. Pretreatment of mice with HHQG significantly maintained their body weight and decreased serum tumor necrosis factor-alpha (TNF-α) levels induced by CCl4 treatment in vivo. Histopathological examination further confirmed that HHQG protected the liver cells from CCl4-induced damage. Importantly, HHQG significantly inhibited CCl4-induced monocyte/macrophage infiltration. Transcriptomic analysis revealed that HHQG significantly reduced the expression of chemokines and cell adhesion molecules. We determined that HHQG significantly downregulated the expression of the key chemokine (monocyte chemokine protein-1, CCL2) at the gene and protein levels. Further research showed that HHQG inhibited chemokine production in hepatocytes by inhibiting the p-P38 and p-JNK pathways, thereby reducing monocyte/macrophage infiltration. CONCLUSIONS: These combined data showed that HHQG alleviated acute liver injury in mice, and further verified that HHQG exerted protective effects by inhibiting the production of CCL2 and reducing the infiltration of monocyte/macrophage by inhibiting the p-P38 and p-JNK pathways.