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Acute kidney injury (AKI) emerges as an acute and critical disease. Tripartite motif 8 (TRIM8), one number of the TRIM protein family, is proved to participate in ischemia/reperfusion (I/R) injury. However, whether TRIM8 is involved in renal I/R injury and the associated mechanisms are currently unclear. This study aimed to investigate the precise role of TRIM8 and relevant mechanisms in renal I/R injury. In this study, human renal proximal tubular epithelial cells (HK-2 cells) underwent 12 hours of hypoxia and 2 h, 3 h or 4 h of reoxygenation to establish an in vitro hypoxia/reoxygenation (H/R) model. The siRNAs specific to TRIM8 (si-TRIM8) were transfected into HK-2 cells to knockdown TRIM8. The cell H/R model included various groups including Control, H/R, H/R+DMSO, H/R+NAC, si-NC+H/R, si-TRIM8+H/R and si-TRIM8+LY294002+H/R. The cell viability and levels of reactive oxygen species (ROS), hydrogen peroxide (H O ), mRNA, apoptotic proteins, pyroptosis-related proteins and PI3K/AKT pathway-associated proteins were assessed. In vitro, realtime-quantitative PCR and western-blot analysis showed that the mRNA and protein expression of TRIM8 were obviously upregulated after H/R treatment in HK-2 cells. Compared with the H/R model group, knockdown of TRIM8 significantly increased cell viability and reduced the levels of ROS, H O , apoptotic proteins (Cleaved caspasebase-3 and BAX) and pyroptosis-related proteins (NLRP3, ASC, Caspase-1, Caspase-11, IL-1β and GSDMD-N). Western-blot analysis also authenticated that PI3K/AKT pathway was activated after TRIM8 inhibition. The application of 5 mM N-acetyl-cysteine, one highly efficient ROS inhibitor, significantly suppressed the expression of apoptotic proteins and pyroptosis-related proteins. Moreover, the combined treatment of TRIM8 knockdown and LY294002 reversed the effects of inhibiting oxidative stress. Knockdown of TRIM8 can alleviate H/R-induced oxidative stress by triggering the PI3K/AKT pathway, thus attenuating pyropyosis and apoptosis in vitro.

Background Anomalous drainage of the ductus venosus (DV) into the coronary sinus (CS) is a rare fetal vascular anomaly that poses challenges for prenatal diagnosis. This study aimed to investigate the role of two-dimensional (2D) and three-dimensional (3D) ultrasound imaging, specifically spatiotemporal image correlation (STIC) technology, in improving the prenatal diagnosis of this anomaly. Methods We retrospectively reviewed eight cases of fetuses diagnosed with anomalous DV drainage into the CS at Gansu Provincial Maternal and Child Health Hospital between September 2019 and September 2024. The gestational age of the fetuses ranged from 24 to 30 weeks. Ultrasound examinations, including 2D and Doppler imaging, along with HDlive Flow combined with STIC technology, were used for diagnosis. Differential diagnoses were made based on imaging findings. Descriptive statistics were employed to summarize the results. Results Eight fetuses with anomalous DV drainage into the CS were identified. Of these, five cases were isolated anomalies, while three had associated malformations, such as aberrant right subclavian artery and right aortic arch. Dilated CS was observed in all cases, with an average inner diameter of 5.7 mm. STIC imaging successfully visualized the abnormal course of the DV, enhancing diagnostic confidence. Postnatal follow-up indicated favorable outcomes for most neonates (except for Case NO.3 and Case NO.7), although persistent CS dilation was observed in these cases, without significant hemodynamic compromise or clinical symptoms. Conclusions Prenatal diagnosis of anomalous DV drainage into the CS can be effectively achieved using 2D and 3D ultrasound, with STIC technology providing added diagnostic clarity. Early and accurate detection is crucial for ensuring appropriate clinical management and favorable outcomes. Ongoing surveillance of CS dilation in the postnatal period is recommended.

Prostate cancer (PCa) is the most common male genitourinary malignancy in the world. The protein arginine methyltransferase 5 (PRMT5) is one of the main members of the type II PRMT family, which was reported to regulate androgen-dependent PCa cell proliferation. However, the upstream regulators of PRMT5 and its effects on androgen-independent PCa metastasis remained unclear. In the present study, we investigated whether PRMT5 could be a novel diagnostic marker and be used as a therapeutic target in PCa, to explore the possible molecular mechanism, and to understand the clinical importance of PRMT5 in PCa. The present study evaluated PRMT5 expression levels in PCa and normal prostate samples using public datasets, including TCGA, GEPIA and GSE21032. Furthermore, CCK-8 assay, flow cytometer assay, and transwell assay were conducted to detect the roles of PRMT5. Luciferase reporter assay was used to determine the relationship among ZFAS1/miR-150-5p/PRMT5. Our results showed that PRMT5 was overexpressed in PCa samples. PRMT5 significantly promoted androgen-dependent PCa proliferation and cell cycle progression and suppressed cell apoptosis. However, PRMT5 did not affect androgen-independent PCa proliferation but it could significantly induce androgen-independent PCa metastasis. Knockdown of PRMT5 suppressed, whereas overexpression of PRMT5 induced, cell migration and invasion in androgen-independent DU145 and PC-3 cells. Moreover, our results showed that the ZFAS1/miR-150-5p axis regulated PRMT5 expression in PCa cells. Furthermore, the study showed that ZFAS1 and PRMT5 were overexpressed and miR-150-5p was down-regulated in PCa samples. Higher expression levels of ZFAS1 and PRMT5 were correlated with shorter disease-free survival time in PCa patients. These results showed that PRMT5 may be a therapeutic target for PCa.

A total of 138 cDEGs were screened from mediastinal lymph nodes and peripheral whole blood. Among them, 6 hub cDEGs including CTSS, CYBB, FPR2, MNDA, TLR1 and TLR8 with elevated degree and betweenness levels were illustrated in protein-protein interaction network. In comparison to healthy controls, CTSS (1.61 vs. 1.05), CYBB (1.68 vs. 1.07), FPR2 (2.77 vs. 0.96), MNDA (2.14 vs. 1.23), TLR1 (1.56 vs. 1.09), and TLR8 (2.14 vs. 0.98) displayed notably elevated expression levels within pulmonary sarcoidosis PBMC samples (P < 0.0001 for FPR2 and P < 0.05 for others), echoing with prior mRNA microarray findings. The most significant functional pathways were immune response, inflammatory response, plasma membrane and extracellular exosome, with 6 hub cDEGs distributing along these pathways. CTSS, CYBB, FPR2, MNDA, TLR1, and TLR8 could be conducive to improving the diagnostic process and understanding the underlying mechanisms of pulmonary sarcoidosis.

Silicosis is an occupational lung disease caused by inhalation of silica dust characterized by lung inflammation and fibrosis. Previous study showed that Th1 and Th2 cytokines are involved in silicosis, but Th1/Th2 polarization during the development of silicosis is still a matter of debate. Regulatory T cells (Treg cells) represent a crucial role in modulation of immune homeostasis by regulating Th1/Th2 polarization, but their possible implication in silicosis remains to be explored. To evaluate the implication of Treg cells in the development of silicosis, we generated the Treg-depleted mice model by administration of anti-CD25 mAbs and mice were exposed to silica by intratracheal instillation to establish experimental model of silica-induced lung fibrosis. The pathologic examinations show that the Treg-depleted mice are susceptive to severer inflammation in the early stage, with enhanced infiltration of inflammatory cells. Also, depletion of Treg cells causes a delay of the progress of silica-induced lung fibrosis in mice model. Further study of mRNA expression of cytokines reveals that depletion of Tregs leads to the increased production of Th1-cytokines and decreased production of Th2-cytokine. The Flow Cytometry and realtime PCR study show that Treg cells exert the modulation function both directly by expressing CTLA-4 at the inflammatory stage, and indirectly by secreting increasing amount of IL-10 and TGF-β during the fibrotic stage in silica-induced lung fibrosis. Our study suggests that depletion of Tregs may attenuate the progress of silica-induced lung fibrosis and enhance Th1 response and decelerate Th1/Th2 balance toward a Th2 phenotype in silica-induced lung fibrosis. The regulatory function of Treg cells may depend on direct mechanism and indirect mechanism during the inflammatory stage of silicosis.

The aim of the present study was to design a novel topical skin-target drug-delivery system, the paeonol microsponge, and to investigate its drug-release patterns in dosage form, both in vitro and in vivo. Paeonol microsponges were prepared using the quasi-emulsion solvent-diffusion method. In vitro release studies were carried out using Franz diffusion cells, while in vivo studies were investigated by microdialysis after the paeonol microsponges were incorporated into a cream base. In vitro release studies showed that the drug delivered via microsponges increased the paeonol permeation rate. Ex vivo drug-deposition studies showed that the microsponge formulation improved drug residence in skin. In addition, in vivo microdialysis showed that the values for the area under the concentration versus time curve (AUC) for the paeonol microsponge cream was much higher than that of paeonol cream without microsponges. Maximum time (Tmax) was 220 min for paeonol microsponge cream and 480 min for paeonol cream, while the half-life (t1/2) of paeonol microsponge cream (935.1 min) was almost twice that of paeonol cream (548.6 min) in the skin (n = 3). Meanwhile, in the plasma, the AUC value for paeonol microsponge cream was half that of the paeonol cream. Based on these results, paeonol-loaded microsponge formulations could be a better alternative for treating skin disease, as the formulation increases drug bioavailability by lengthening the time of drug residence in the skin and should reduce side-effects because of the lower levels of paeonol moving into the circulation.

Ovarian cancer patients undergoing cytoreductive surgery are prone to hypovolemic shock in the early postoperative period, resulting in tissue hypoperfusion, lactic acid accumulation, endotoxin displacement, and even multiple organ dysfunction syndrome; however, in existing studies, there is a lack of a dynamic approach to assess the risk of postoperative hypovolemic shock. This study aimed to construct and validate a visual prediction model of hypovolemic shock after cytoreductive surgery. This is a retrospective observational study. Patients with ovarian cancer who received cytoreductive surgery at Zhejiang Cancer Hospital between January 2023 and June 2024 were retrospectively enrolled and divided into a training group and a validation group. Independent predictors of hypovolemic shock were identified using least absolute shrinkage and selection operator (LASSO) regression from the training set, and a nomogram was constructed based on these predictors. A nomogram was used to depict the weight of each variable in the logistic regression model on the event occurrence. The performance of the nomogram was assessed using receiver operating characteristic (ROC), calibration curve, and decision curve analysis (DCA). A total of 423 patients were eligible for inclusion in this study. There were 301 cases in the training group and 122 cases in the validation group. This visual prediction model was constructed based on the duration of the operation (odds ratio (OR) = 1.273; 95% confidence interval (CI) [1.052-1.552]), the amount of blood lost during the operation (OR = 1.102; 95% CI [1.020-1.196]), the amount of albumin (OR = 0.935; 95% CI [0.879-0.993]) and fibrinogen (OR = 0.606; 95% CI [0.371-0.948]) immediately after the operation, and the postoperative use of sedative drugs (OR = 2.248; 95% CI [1.109-4.538]). The area under the ROC of the nomogram for the training and validation cohorts was 0.800 (95% CI [0.740-0.860]) and 0.821 (95% CI [0.735-0.907]), respectively. The predicted probabilities of the two groups of models were basically consistent with the actual incidence rates, with the average absolute errors being 0.016 and 0.019, respectively. The Hosmer-Lemeshow test of the training group (  = 0.722) and the validation group (  = 0.565) showed that there was no significant difference between the predicted values and the actual values, indicating that the model fitted well. The results of the DCA curve showed that the two groups had a net benefit within the probability range of risk threshold values of 0.01 to 0.84 and 0.04 to 0.80, respectively. The model constructed in this study demonstrates improved predictive accuracy for the risk of hypovolemic shock after cytoreductive surgery in patients with ovarian cancer, and it holds the potential to provide a basis for medical staff to achieve early identification and timely intervention.

Prostate cancer (PCa) is one of the most common cancer in males. Previous studies indicated that MIR22HG was a tumor suppressor in various cancers. However, the expression pattern and functional roles of MIR22HG in PCa remained to be further investigated. In this study, we for the first time showed MIR22HG was down-regulated in PCa. Furthermore, we observed the lower expression levels of MIR22HG were significantly related to higher Gleason score and T stage. Of note, we found that higher MIR22HG expression was associated with better disease-free survival and overall survival time in PCa. Moreover, we constructed a MIR22HG mediated co-expression network. Bioinformatics analysis showed MIR22HG was associated with regulating inflammatory response, regulation of transcription, cellular response to tumor necrosis factor, neutrophil chemotaxis, cell-cell signaling, and TNF signaling pathway. These results showed that MIR22HG could serve as a novel biomarker for prostate cancer.

The management of bronchiectasis-asthma overlap (BAO) is an important clinical issue to be addressed. Little is known regarding the endotype of BAO. Here we recruit patients with a primary diagnosis of bronchiectasis and co-existing asthma. The levels of interleukin (IL)-17C are positively correlated with the levels of IL-17A or group 3 innate lymphoid cells (ILC3s) in peripheral blood samples from patients with BAO. An in vivo mouse model of Pseudomonas aeruginosa chronic lower respiratory tract infection followed by ovalbumin-induced asthma shows that IL-17C potentiates IL-17A expression via interacting with IL-17 receptor E in ILC3s. Additionally, ablation of Il17re in mice attenuates ILC3 responses and IL-17A-mediated asthma endotype switching towards neutrophilic asthma driven by P. aeruginosa chronic lower respiratory tract infection. Lastly, impaired epithelial barrier integrity by P. aeruginosa exposure is associated with IL-17C production in vitro. Collectively, our study implicates evidence for IL-17C governing IL-17A pathogenicity and promoting asthma endotype switching in bronchiectasis, implicating IL-17C as a potential therapeutic target for individuals with BAO. Bronchiectasis and asthma can co-exist in the same patient, and the characteristics may be different from bronchiectasis alone. Here the authors characterise the function of ILC3 cells and how IL-17C potentiates IL-17A expression promoting a neutrophil dominated asthma endotype in mouse bronchiectasis-asthma models.

Objective To observe the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for pulmonary alveolar proteinosis (PAP). Materials and methods A total of 55 patients with PAP were screened at Shanghai Pulmonary Hospital between May 2014 and May 2018. Among these, 42 were diagnosed with idiopathic PAP, 24 were included in this study, 20 were treated for 6 months, and 17 were followed up for additional 6 months. All patients received a subcutaneous injection of 75μg/d GM-CSF qd for 1 month. The therapeutic dose was adjusted according to the changes in the lesions of chest CT. If the lesions were absorbed, subcutaneous injections of 75μg/d GM- CSF qd and 75μg/d GM-CSF qod were given for 2 and 3 months, otherwise, the dose was increased to 150μg/d GM-CSF qd and 150μg/d qod for 2 and 3 months, respectively. All cases were treated once a day in the first 3 months and once every other day in the last 3 months. The total course of treatment was 6 months. After withdrawal, the patients were followed up for another 6 months. The deadline of follow up was September 30, 2019. Results Twenty patients completed the treatment and efficacy evaluation. One patient was completely cured, 16 cases improved, three cases were noneffective. After 1-month evaluation, 12 patients received an increased dose (150μg) from the second month of treatment. Seventeen patients completed the 12-month follow-up, among which fourteen improved. CT showed the lesions were slightly increased in three cases. Economic burden was the following: RMB 7324–15,190 Yuan were required for the 6-month treatment course, which is significantly lower compared to other treatment methods. Conclusion Subcutaneous injection of rhGM-CSF at low dose (75μg-150μg /d) is effective treatment for patients with idiopathic PAP. Trial registration NCT01983657 . Registered 16 April 2013.