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Objective To detect the alterations of the transcriptome in host cells infected by enterovirus D68 (EV-D68) and look for the genes involved in its infection so as to lay a foundation for the preliminary exploration of the infection mechanism. Methods The virus was inoculated into human rhabdomyosarcoma (RD) cells at a multiplicity of infection (MOI) of 0.01. After 24 h, RNA was extracted from the infected RD cells and control cells for transcriptome sequencing. Differentially expressed genes (DEGs) were screened and analyzed by using Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Eight DEGs, EGR1, c-fos, ZNF625, ARRDC3, c-jun, ASNS, CHAC1 and ADM2 were validated by RT-qPCR. Results A total of 140 genes with at least 2-fold changes at expression level were identified from the sequencing results, of which 71 were up-regulated and 69 were down-regulated. The results of GO functional enrichment analysis mainly involved the regulation and response to ions while the results of KEGG enrichment analysis mainly related to parathyroid hormone synthesis, secretion and action, IL-17 and GnRH signaling pathway, Toll-like receptor signaling pathway, and MAPK signaling pathway and so on. The RT-qPCR results showed that the trend of fold change of expression in the selected 8 genes was basically consistent with the sequencing results, and the expression levels of c-fos and c-jun were increased with the increase of virus MOI and infection duration. Conclusion By validating and using the functional and enrichment analysis, we infer that the mechanism of EV-D68 exacerbating asthma may be related to the up-regulation of c-fos, and MAPK signaling pathway may play a pro-inflammatory and antiviral role during EV-D68 infection.

The benefit of endovascular treatment (EVT) for patients with intracranial atherosclerosis–related large vessel occlusion (ICAS-LVO) in posterior circulation stroke (PCS) is inconsistent. This systematic review and meta-analysis were conducted to estimate the effect of ICAS-LVO in PCS treated by EVT. A systematic review was completed, tracking studies from their date of inception until February 2020. Clinical studies which compared outcomes after EVT for ICAS-LVO and non–ICAS-LVO in PCS were included. Data were synthesized and interpreted from meta-analysis. A total of 688 patients (352 ICAS-LVO and 336 non–ICAS-LVO) in the eight studies were included. The successful reperfusion rate (odds ratio [OR], 0.58; 95% confidence intervals [95% CIs], 0.37–0.93; P = 0.02) was lower in PCS with ICAS-LVO than non–ICAS-LVO. And for other clinical outcomes, there were no differences between both groups. Moreover, there were no statistical differences of any clinical outcome among subgroups stratified by nations and target vessel occlusion location. With respect to patients' characteristics, age (mean difference [MD], −2.75; 95% CI, −4.62–−0.88; P = 0.004), pc-Alberta Stroke Program Early CT Score (MD, −0.49; 95% CI, −0.94–−0.05; P = 0.03), distributions of sex (male) (OR, 2.34; 95% CI, 1.53–3.56; P < 0.001), prior or current smoking (OR, 1.85; 95% CI, 1.12–3.07; P = 0.02), hypertension (OR, 2.06; 95% CI, 1.32–3.22; P = 0.002), coronary artery disease (OR, 0.27; 95% CI, 0.11–0.66; P = 0.004) and general anesthesia (OR, 2.89; 95% CI, 1.54–5.45; P = 0.001) were statistically different between both groups. In conclusion, more targeted assessments are warranted for patients with ICAS-LVO–related PCS during clinical strategies, and the benefit of EVT for PCS with ICAS-LVO deserves further research. [ABSTRACT FROM AUTHOR]

Background: Extracranial malignant rhabdoid tumors (eMRTs) are rare, highly aggressive neoplasms, predominantly arising in the kidneys, with bladder involvement being extremely uncommon. Optimal management strategies, particularly bladder-preserving approaches, are not well-established due to the rarity of these cases., Case Description: We report the case of a 4-year-old girl who presented with persistent gross hematuria. Imaging revealed a large bladder mass and histopathological examination confirmed the diagnosis of an extrarenal rhabdoid tumor with loss of SMARCB1 expression. The patient underwent a multimodal treatment approach, including bladder-preserving surgery, 12 cycles of high-dose MRTK-2020 neoadjuvant chemotherapy [comprising actinomycin D, vincristine, doxorubicin, cyclophosphamide (AVDC), ifosfamide, carboplatin, and etoposide (ICE)], followed by adjuvant radiotherapy. Remarkably, the patient achieved complete remission after two cycles of chemotherapy and remained in continuous remission with no evidence of disease at the 15-month follow-up., Conclusions: This case underscores the diagnostic challenges of malignant rhabdoid tumors (MRTs) in bladder pathologies and highlights the significance of considering such tumors in differential diagnoses. Despite the limited evidence base, bladder-preserving surgeries, when feasible, should be considered and accompanied by adjuvant therapies for optimal outcomes. This case illustrates the potential for successful treatment of pure MRTs of the bladder using a combination of surgery, chemotherapy, and radiotherapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-24-255/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background: Neutrophil-To-Albumin Ratio (NAR) is a novel inflammatory biomarker. However, the potential prognostic value of NAR in acute ischemic stroke (AIS) remains unclear. This study aimed to evaluate whether NAR levels correlated with the 3-month modified Rankin scale (mRS) in patients with AIS., Methods: AIS patients were included in this retrospective study. NAR was calculated as the ratio of absolute neutrophil count to serum albumin level. Logistic regression analyses were used to investigate the effect of NAR on 3-month mRS of AIS. The predictive values of NAR, albumin level, and neutrophil count were compared utilizing receiver operating characteristic (ROC) curves. Moreover, subgroup analyses and interaction tests were conducted to evaluate the consistency of NAR's effect on AIS prognosis., Results: Of the 780 patients included, 403 (51.67%) had a poor clinical outcome (mRS 3-6) at 3 months. NAR was independently correlated to 3-month poor functional outcome after adjusting for confounders (Odds ratios (OR), 9.34; 95% confidence intervals (CI), 1.09 to 80.13; p =0.0417). Subgroup analysis showed a relative effect consistent with the overall population results, and no statistical interactions were found in the subgroups (all p for interaction > 0.05). The ROC curve showed that the prognosis-related cutoff value for NAR was 0.123, with corresponding specificity and sensitivity of 53.55% and 63.94%, respectively. When comparing the predictive power, NAR (0.590; 95%CI 0.549-0.630) exhibited the highest area under the curve (AUC) of ROC compared to neutrophils (0.584; 95%CI 0.543-0.624) and albumin (0.540; 95%CI 0.500-0.581)., Conclusion: There is a positive relationship between NAR levels and 3-month poor functional outcomes in AIS patients, supporting the potential of NAR as a readily available and economic serum biomarker for the early identification of AIS prognosis. Further studies are required to validate the prognostic value and clinical utility of the NAR., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Among the PLWH (people living with HIV) population, the risk of developing active tuberculosis (TB) is increasing. Active TB also accelerates the deterioration of PLWH's immune function and is one of the leading causes of death in the PLWH population. So far, accurate diagnosis of active TB in the PLWH population remains challenging. Through data analysis of HIV/TB co-infection in the GEO database, the differentially expressed genes as well as their related microRNA (miRNA) were acquired and were further verified through clinical blood samples. Dual-luciferase assay was used to verify the mechanism of miRNA on mRNA. The enrichment of immune cells in database patient samples was analyzed by bioinformatics and finally verified by blood routine data. Our study found that FKBP5 (FK506 binding protein 5) was highly expressed in the HIV/TB co-infection group; hsa-miR-320a-3p was highly expressed in the HIV infection group but decreased in the HIV/TB co-infection group. Dual-luciferase assay results showed that hsa-miR-320a-3p mimics significantly reduced the relative luciferase activity of the WT-FKBP5 group; however, this phenomenon was not observed in the MUT-FKBP5 group. At the same time, as a key molecule of the immune-related pathway, FKBP5 is highly correlated with the amount of neutrophils, which provides a new suggestion for the treatment of the HIV/TB co-infection population. Our study found that hsa-miR-320a-3p can decrease FKBP5 expression, suggesting a potential regulatory role for FKBP5. The involvement of FKBP5 and its related molecule hsa-miR-320a-3p in HIV/TB co-infection proposes them as potential biomarkers for the diagnosis of active TB in the PLWH population.

Introduction: Spontaneous vertebral artery dissection (sVAD) might tend to develop in vertebral artery hypoplasia (VAH) with hemodynamic dysfunction and it is crucial to assess hemodynamics in sVAD with VAH to investigate this hypothesis. This retrospective study aimed to quantify hemodynamic parameters in patients with sVAD with VAH., Methods: Patients who had suffered ischemic stroke due to an sVAD of VAH were enrolled in this retrospective study. The geometries of 14 patients (28 vessels) were reconstructed using Mimics and Geomagic Studio software from CT angiography (CTA). ANSYS ICEM and ANSYS FLUENT were utilized for mesh generation, set boundary conditions, solve governing equations, and perform numerical simulations. Slices were obtained at the upstream area, dissection or midstream area and downstream area of each VA. The blood flow patterns were visualized through instantaneous streamline and pressure at peak systole and late diastole. The hemodynamic parameters included pressure, velocity, time-averaged blood flow, time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), endothelial cell action potential (ECAP), relative residence time (RRT) and time-averaged nitric oxide production rate (TAR NO )., Results: Significant focal increased velocity was present in the dissection area of steno-occlusive sVAD with VAH compared to other nondissected areas (0.910 m/s vs. 0.449 vs. 0.566, p  < 0.001), while focal slow flow velocity was observed in the dissection area of aneurysmal dilatative sVAD with VAH according to velocity streamlines. Steno-occlusive sVAD with VAH arteries had a lower time-averaged blood flow (0.499 cm 3 /s vs. 2.268, p  < 0.001), lower TAWSS (1.115 Pa vs. 2.437, p = 0.001), higher OSI (0.248 vs. 0.173, p  = 0.006), higher ECAP (0.328 Pa -1 vs. 0.094, p  = 0.002), higher RRT (3.519 Pa -1 vs. 1.044, p  = 0.001) and deceased TAR NO (104.014 nM/s vs. 158.195, p  < 0.001) than the contralateral VAs., Conclusion: Steno-occlusive sVAD with VAH patients had abnormal blood flow patterns of focal increased velocity, low time-averaged blood flow, low TAWSS, high OSI, high ECAP, high RRT and decreased TAR NO . These results provide a good basis for further investigation of sVAD hemodynamics and support the applicability of the CFD method in testing the hemodynamic hypothesis of sVAD. More detailed hemodynamic conditions with different stages of sVAD are warranted in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bao, Gan, Feng, Li, Qiu, Zhou, Guo and He.)

Objective To investigate the anti-DNA damage role of Sigma factor E (SigE) and its regulation mechanism of DNA damage repair in Mycobacterium smegmatis(MS). Methods The SigE gene of Mycobacterium smegmatis was cloned into plasmid pMV261 to construct recombinant plasmid pMV261(+)-SigE, and the inserted gene was verified by sequencing. The recombinant plasmid was electrically transformed into Mycobacterium smegmatis to construct SigE over-expression strain, and the expression of SigE was detected by Western blot analysis. The Mycobacterium smegmatis containing pMV261 plasmid was used as the control strain. Growth differences between the two stains were monitored by measuring the 600 nm absorbance (A 600 ) value of the bacterial culture suspension. The survival rate differences between two kinds of strains which were treated with three kinds of DNA damaging agents including ultraviolet ray (UV), cisplatin (DDP), and mitomycin C (MMC) were detected by colony forming unit (CFU) counting assay. DNA damage repair pathways of Mycobacteria were analyzed through bioinformatics and SigE-related genes were screened. The relative expression levels of these genes possibly related to the SigE against DNA damage were detected by real-time fluorescence quantitative PCR. Results SigE over-expression strain pMV261(+)-SigE/MS was constructed and the expression of SigE in Mycobacterium smegmatis was detected. Compared with the control strain, the SigE over-expression strain grew more slowly and entered the growth plateau later; survival rate analysis found that SigE over-expression strain was more resistant to three DNA damaging agents including UV, DDP, and MMC. Bioinformatic analysis indicated that SigE gene was closely related to DNA damage repair genes recA, single-strand DNA binding protein, (ssb), and dnaE2; the expression levels of recA, dnaE2, and ssb in SigE over-expression strain all increased with varying degrees compared with those in the control strain. Conclusion SigE plays an important role in inhibiting the DNA damage of Mycobacterium smegmatis, whose mechanism is closely related to the regulation of DNA damage repair.