Unraveling the role of the circadian clock genes in cervical squamous cell carcinoma and endocervical adenocarcinoma: A prognostic indicator for prognostic, immunotherapy response, and chemotherapy sensitivity.

Background: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) account for a significant proportion of gynecological malignancies and represent a major global health concern. Globally, CESC is ranked as the fourth most common cancer among women. Conventional treatment of this disease has a less favorable prognosis for most patients. However, the discovery of early molecular biomarkers is therefore important for the diagnosis of CESC, as well as for slowing down their progression process. Methods: To identify differentially expressed genes strongly associated with prognosis, univariate Cox proportional hazard analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were used. Using multiple Cox proportional hazard regression, a multifactorial model for prognostic risk assessment was then created. Results: The expression of biological clock-related genes, which varied considerably among distinct subtypes and were associated with significantly diverse prognoses, was used to categorize CESC patients. These findings demonstrate how the nomogram developed based on the 7-CRGs signature may assist physicians in creating more precise, accurate, and successful treatment plans that can aid CESC patients at 1, 3, and 5 years. Conclusions: By using machine learning techniques, we thoroughly investigated the impact of CRGs on the prognosis of CESC patients in this study. By creating a unique nomogram, we were able to accurately predict patient prognosis. At the same time, we showed new perspectives on the development of CESC and its treatment by analyzing the associations of the prognostic model with immunity, enrichment pathways, chemotherapy sensitivity, and so on. This research provides a new direction for clinical treatment.

Cerebral blood vessels and perfusion in the pediatric brain death: five cases studied by neuroimaging.

PURPOSE: To detect the cerebral blood vessels and perfusion using neuroimaging modalities including computed tomography angiography (CTA), computed tomography perfusion (CTP), and arterial spin labeling (ASL) in children with brain death (BD). METHODS: According to the current children's BD criteria, 5 children (3 males, 2 females, mean age of 5.65 years) with BD were enrolled from January 2019 to December 2020. The imaging features of CTA, CTP, and ASL were evaluated to analyze the visualization of important intracranial blood vessels and the states of the cerebral blood flow (CBF) and cerebral blood volume (CBV) related to the region of interest (ROI) brain tissue during the two clinical assessments for BD. RESULTS: The "4-point scale" scoring system of CTA was applied to evaluate BD and no negative results were detected. The CTP results of the 5 children suggested the cessation of cerebral circulation with 100% positive results. The ranges of CBF and CBV were 0.00-9.52 ml/100 g/min (mean value 4.95 ± 1.69 ml/100 g/min) and 0.00-1.34 ml/100 g (mean value 0.36 ± 0.20 ml/100 g), respectively. One patient also underwent ASL examination, which demonstrated a significant reduction in whole brain perfusion, indicating the absence of cerebral circulation. The CBF values of the brainstem, basal ganglia, and prefrontal lobe were 11.61 ± 1.49 ml/100 g/min, 7.81 ± 2.42 ml/100 g/min, and 9.94 ± 2.01 ml/100 g/min, respectively. CONCLUSION: Neuroimaging examinations particularly CTA and CTP reveal well the hemodynamic and cerebral blood vessels changes of BD, which can be used as supplementary supportive evidence for the declaration of brain death in children.

Effect of Intraoperative Ventilation Strategies on Postoperative Pulmonary Complications: A Meta-Analysis.

Introduction: The role of intraoperative ventilation strategies in subjects undergoing surgery is still contested. This meta-analysis study was performed to assess the relationship between the low tidal volumes strategy and conventional mechanical ventilation in subjects undergoing surgery. Methods: A systematic literature search up to December 2020 was performed in OVID, Embase, Cochrane Library, PubMed, and Google scholar, and 28 studies including 11,846 subjects undergoing surgery at baseline and reporting a total of 2,638 receiving the low tidal volumes strategy and 3,632 receiving conventional mechanical ventilation, were found recording relationships between low tidal volumes strategy and conventional mechanical ventilation in subjects undergoing surgery. Odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CIs) were calculated between the low tidal volumes strategy vs. conventional mechanical ventilation using dichotomous and continuous methods with a random or fixed-effect model. Results: The low tidal volumes strategy during surgery was significantly related to a lower rate of postoperative pulmonary complications (OR, 0.60; 95% CI, 0.44-0.83, p < 0.001), aspiration pneumonitis (OR, 0.63; 95% CI, 0.46-0.86, p < 0.001), and pleural effusion (OR, 0.72; 95% CI, 0.56-0.92, p < 0.001) compared to conventional mechanical ventilation. However, the low tidal volumes strategy during surgery was not significantly correlated with length of hospital stay (MD, -0.48; 95% CI, -0.99-0.02, p = 0.06), short-term mortality (OR, 0.88; 95% CI, 0.70-1.10, p = 0.25), atelectasis (OR, 0.76; 95% CI, 0.57-1.01, p = 0.06), acute respiratory distress (OR, 1.06; 95% CI, 0.67-1.66, p = 0.81), pneumothorax (OR, 1.37; 95% CI, 0.88-2.15, p = 0.17), pulmonary edema (OR, 0.70; 95% CI, 0.38-1.26, p = 0.23), and pulmonary embolism (OR, 0.65; 95% CI, 0.26-1.60, p = 0.35) compared to conventional mechanical ventilation. Conclusions: The low tidal volumes strategy during surgery may have an independent relationship with lower postoperative pulmonary complications, aspiration pneumonitis, and pleural effusion compared to conventional mechanical ventilation. This relationship encouraged us to recommend the low tidal volumes strategy during surgery to avoid any possible complications.

Deep learning-based methods may minimize GBCA dosage in brain MRI.

OBJECTIVES: To evaluate the clinical performance of a deep learning (DL)-based method for brain MRI exams with reduced gadolinium-based contrast agent (GBCA) dose to provide better understanding of the readiness and limitations of this method. METHODS: Eighty-three consecutive patients (from March 2019 to August 2019) who underwent brain contrast-enhanced (CE) MRI were included. Three 3D T1-weighted images with zero-dose, low-dose (10%), and full-dose (100%) GBCA were collected. The first 30 cases were used to train a DL model to synthesize the full-dose GBCA images from the zero-dose and low-dose image pairs. The remaining 53 cases were used for testing. The enhancement pattern, number, and location of enhancing lesions were recorded. Overall image quality, image signal noise ratio (SNR), lesion conspicuity, and lesion enhancement were assessed. RESULTS: Lesion detection from the DL-synthesized CE-MRI image accurately matched those from the true full-dose CE-MRI images in 48 of 53 cases (90.6%). The DL method identified the lesions in 34 of 36 cases (94.4%) with a single enhanced lesion and all lesions in 3 of 6 cases (50.0%) in cases with multiple enhancing lesions. The agreement between synthesized and true full-dose CE-MRI images were 0.73, 0.63, 0.89, and 0.87 for image quality, image SNR, lesion conspicuity, and lesion enhancement, respectively. CONCLUSIONS: The proposed DL method is a feasible way to minimize the dosage of GBCAs in brain MRI without sacrificing the diagnostic information. Missing enhancement of small lesions in patients with multiple lesions was observed, requiring improvements in algorithms or dosage design. KEY POINTS: • This study evaluated the clinical performance of a DL-based reconstruction method for significant dose reduction in GBCA contrast-enhanced MRI exams. • The proposed DL method has the potential to satisfy the routine radiological diagnosis needs in certain clinical applications.

JNK­IN­8 treatment alleviates lipopolysaccharide­induced acute lung injury via suppression of inflammation and oxidative stress regulated by JNK/NF­κB signaling.

JNK serves critical roles in numerous types of inflammation­ and oxidative stress­induced disease, including acute lung injury (ALI). JNK­IN­8 is the first irreversible JNK inhibitor that has been described. However, whether JNK­IN­8 can prevent lipopolysaccharide (LPS)­induced ALI by inhibiting JNK activation and its downstream signaling is poorly understood. The objective of the present study was to investigate the specific therapeutic effects of JNK­IN­8 on LPS­induced ALI and the molecular mechanisms involved. JNK­IN­8 attenuated myeloperoxidase activity, malondialdehyde and superoxide dismutase content and the lung wet/dry ratio, and improved the survival rate following lethal injection of LPS. Additionally, JNK­IN­8 decreased bronchoalveolar lavage fluid protein levels, lactate dehydrogenase activity, neutrophil infiltration and the number of macrophages (as demonstrated by flow cytometry), as well as the production of TNF­α, IL­6 and IL­1ß (as evaluated via ELISA). In addition, reverse transcription­quantitative PCR and ELISA showed that JNK­IN­8 attenuated LPS­induced inflammatory cytokine production and oxidative stress in primary murine peritoneal macrophages and RAW264.7 cells in vitro. Furthermore, the present study demonstrated that the JNK/NF­κB signaling pathway was involved in the therapeutic effect of JNK­IN­8 against LPS­induced injury both in vivo and in vitro. In conclusion, these findings indicated that JNK­IN­8 had a therapeutic effect on LPS­induced ALI in mice. The mechanism may be associated with inhibition of the JNK/NF­κB signaling pathway. JNK­IN­8 may be a potential therapeutic agent for the treatment of ALI.

Pretreatment with AM1241 Enhances the Analgesic Effect of Intrathecally Administrated Mesenchymal Stem Cells.

Mesenchymal stem cells have cannabinoid (CB) receptors type 1 and type 2 and can alleviate a variety of neuropathic pains, including chronic constriction injury (CCI). A selective CB2 receptor agonist is AM1241. In the present study, it was found that mice with CCI displayed a longer duration of mechanical and thermal analgesia when intrathecally (i.t.) injected with AM1241-treated mesenchymal stem cells, compared to those injected with untreated mesenchymal stem cells or AM1241 alone. Moreover, CCI-induced upregulation of the phosphorylated extracellular signal-regulated kinase (ERK) 1/2 (p-ERK1/2) was inhibited following i.t. injection of AM1241-treated mesenchymal stem cells and this inhibition was noticeably higher compared to injection with untreated mesenchymal stem cells. The expression of transforming growth factor-ß1 (TGF-ß1) was also analyzed in the dorsal root ganglion (DRGs) and spinal cord of CCI mice. In untreated CCI mice, expression of TGF-ß1 was increased, whereas pretreatment with AM1241-treated mesenchymal stem cells regulated the expression of TGF-ß1 on 10 days and 19 days after surgery. In addition, i.t. injection of exogenous TGF-ß1 slightly alleviated neuropathic pain whilst neutralization of TGF-ß1 potently blocked the effect of AM1241-treated mesenchymal stem cells on thermal hyperalgesia and mechanical allodynia of CCI mice. In an in vitro experiment, AM1241 could enhance the release of TGF-ß1 in the supernatant of BMSCs after lipopolysaccharide (LPS) simulation. Taken together, the findings of the current study show that i.t. administration of AM1241-treated mesenchymal stem cells has a positive effect on analgesia and that TGF-ß1 and p-ERK1/2 may be the molecular signaling pathway involved in this process.