Traumatic brain injury (TBI) is a public health concern, and causes cognitive dysfunction, emotional disorders, and neurodegeration, as well. The currently available treatments are all symptom-oriented with unsatifying efficacy. It is highly demanded to understand its underlying mechanisms. Controlled cortical impact (CCI) was used to induce TBI in aged female mice subjected to ovariectomy. Brain damages were assessed with neurological severity score, brain infarction and edema. Morris water maze and elevated plus maze were applied to evaluate the levels of anxiety. Apoptosis in the hippocampus was assayed with Fluoro-Jade B staining and TUNEL staining. Western blot was employed to measure the expression of NMDA receptor subunits and phosphorylation of ERK1/2, and biochemical assays were used to estimate oxidative stress. 17beta-Estradiol (E2) was intraperitoneally administered at 10-80 μg/kg once per day for 7 consecutive days before or after CCI. Chronic administration of E2 both before and immediately after CCI conferred neuroprotection, reducing neurological severity score, brain infarction, and edema in TBI mice. Additionally, E2 improved many aspects of deleterious effects of TBI on the hippocampus, including neuronal apoptosis, dysfunction in spatial memory, reduction in NR2B, enhancement of oxidative stress, and activation of ERK1/2 pathway. The present study provides clue for the notion that E2 has therapeutic potential for both prevention and intervention of TBI-induced brain damages.

The aim of this study was to investigate the effects and the underlying mechanisms of fentanyl anaesthetic on T lymphocytes isolated from human umbilical cord blood in vitro. The percentages of CD4 , CD8 and regulatory T (Treg) cells in human umbilical cord blood mononuclear cells (UBMC) treated with fentanyl in vitro were analysed by flow cytometry. The levels of cytokines IFN-γ, IL-2, IL-4 and IL-17 secreted by activated CD4 T cells were measured by ELISA assays. Expressions of MAPK and NF-κB signalling pathway proteins were determined by Western blotting. Effects of fentanyl on IKK and p65 expression promoter activities were analysed by luciferase assay. Fentanyl decreased the percentages and amounts of CD4 , CD8 and Foxp3 Treg T lymphocyte subsets in UBMCs in a dose-dependent manner. Fentanyl inhibited the proliferation and induced apoptosis of activated CD4 T cells dose dependently. Fentanyl could not reverse the increase of cell proliferation in activated groups to be equivalent with those in inactivated group. Secretions of IFN-γ, IL-2 and IL-4 cytokines were significantly decreased by moderate to high dose of fentanyl compared with controls. No significant differences were observed in protein expressions of MAPK pathway. In addition, fentanyl suppressed the IKKs-mediated activation of NF-κB. This study demonstrates that fentanyl exerts immunosuppressive effects on T lymphocytes obtained from UBMCs. Thus, the clinical application of fentanyl would not only relieve pain caused by surgery but regulate immune responses post-operation possibly through inhibition of IKKs-mediated NF-κB activation.

Background: This systematic review and meta-analysis aimed to assess whether tricuspid annular plane systolic excursion (TAPSE) could be used as a prognostic tool in patients with coronavirus disease 19 .Methods: Studies on the relationship between TAPSE and COVID-19 since February 2021. Standardized mean difference (SMD) and 95% confidence intervals were used to assess the effect size. The potential for publication bias was assessed using a contourenhanced funnel plot and Egger test. A meta-regression was performed to assess if the difference in TAPSE between survivors and nonsurvivors was affected by age, sex, hypertension or diabetes.Results: Sixteen studies comprising 1579 patients were included in this meta-analysis. TAPSE was lower in nonsurvivors (SMD À3.24 (À4.23, À2.26), P < .00001; I 2 = 71%), and a subgroup analysis indicated that TAPSE was also lower in critically ill patients (SMD À3.85 (À5.31, À2.38,), P < .00001; I 2 = 46%). Heterogeneity was also significantly reduced, I 2 < 50%. Pooled results showed that patients who developed right ventricular dysfunction had lower TAPSE (SMD À5.87 (À7.81, À3.92), P = .004; I 2 = 82%). There was no statistically significant difference in the TAPSE of patients who sustained a cardiac injury vs those who did not (SMD À1.36 (À3.98, 1.26), P = .31; I 2 = 88%). No significant publication bias was detected (P = .8147) but the heterogeneity of the included studies was significant. A meta-regression showed that heterogeneity was significantly greater when the incidence of hypertension was <50% (I 2 = 91%) and that of diabetes was <30% (I 2 = 85%). Conclusion:Low TAPSE levels are associated with poor COVID-19 disease outcomes. TAPSE levels are modulated by disease severity, and their prognostic utility may be skewed by pre-existing patient comorbidities.

Accumulating evidence has indicated the crucial role of microRNA-196 in mediating tumor progression, while its significance in cholangiocarcinoma (CCA) remains unclear. In this study, we provided the first evidence that the expression level of miR-196-5p is elevated in both CCA cell lines and clinic specimen. MiR-196-5p inhibition notably suppressed cell proliferation as well as metastasis in CCA cell line HuCCT1. Furthermore, the interaction between miR-196-5p and its downstream molecule HAND1 was verified. Moreover, a series of rescue assay verified that both HAND1 and β-catenin silencing could reverse the abnormal elevated cell proliferation and migration brought by miR-196-5p elevation, indicating that HAND1/Wnt/β-catenin signaling pathway activation is essential for miR-196-5p to exert its roles. In summary, we successfully depict the oncogenic role of miR-196-5p in promoting cell proliferation and migration in CCA via HAND1/Wnt/β-catenin axis.

Objective Histone deacetylase 4 (HDAC4) is engaged in the pathophysiology of acute ischemic stroke (AIS) through modulating atherosclerosis, inflammation and neurocyte death. This study aimed to investigate the clinical role of HDAC4 in AIS. Methods Serum samples were collected from 176 AIS patients and 80 controls for HDAC4 detection by enzyme‐linked immunosorbent assay (ELISA). In AIS patients, disease severity was assessed by National Institute of Health Stroke Scale (NIHSS) score and their recurrence‐free survival (RFS) and overall survival (OS) were calculated, inflammatory cytokines and adhesion molecules were detected by ELISA. Results HDAC4 was declined in AIS patients vs. controls (p < 0.001), it also had certain ability of distinguishing AIS patients from controls with an area under curve of 0.748 (95% confidence interval: 0.689–0.806). Among AIS patients, HDAC4 was negatively linked with NIHSS score (p < 0.001) but no other clinical features (all p > 0.05). Moreover, HDAC4 was negatively related to interleukin (IL)‐17 (p = 0.010) and tumor necrosis factor alpha (p = 0.001), while it was not correlated with IL‐1β (p = 0.081) or IL‐6 (p = 0.074). Furthermore, HDAC4 was negatively associated with intercellular cell adhesion molecule‐1 (p < 0.001) and vascular cell adhesion molecule‐1 (p = 0.003). During a median follow‐up of 19.0 months, 17 (9.7%) patients had recurrence and 10 (5.7%) patients died. Additionally, high HDAC4 was linked with prolonged RFS (p = 0.044) but not OS (p = 0.079). Conclusion HDAC4 possesses the potential to monitor disease risk, inflammation and estimate recurrence of AIS, while further study with larger scale is needed to verify our findings.

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Background Acute respiratory distress syndrome (ARDS) is a severe respiratory disease with a high mortality rate. It is characterized by acute onset of pulmonary edema, hypoxemia, and the need of mechanical ventilation. As the primary treatment, ventilation has been considered effective in treating patients with ARDS. Recently, numerous studies have shown that prone position ventilation demonstrates more efficacy compared with traditional supine position. However, the potential impact of the non‐physiological prone position on patients remains unclear. Current study aims to evaluate the effect of prone position ventilation on right heart function in ARDS patients. Methods Following Berlin Diagnostic Criteria, 80 eligible patients were recruited and randomly assigned into prone position ventilation group and supine position ventilation group. Different ventilation methods were implemented in these two groups. Results Both positions showed the beneficial effects, as evidenced by decreased PV score and APACHE II score, enhanced blood gas index and right heart function parameters, and the prognosis analysis. However, compared with those receiving SPV treatment, the patients demonstrated greater benefits from PPV treatment, with significant differences in PV score (p < 0.01) and APACHE II score (p < 0.001), blood gas index such as PAPm (p < 0.05), and right heart function indicators (p < 0.05). Conclusion Prone position mechanical ventilation is more beneficial than supine position ventilation in improving the blood gas status of patients with moderate to severe ARDS, and it is more helpful to reduce the load on the right heart and promote the recovery of patients.

Cerebral hemorrhage is the most common type of human cerebrovascular disease and frequently causes paralysis, vegetative state and mortality. The modulatory actions of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are vital in the human nervous system. The present study investigated the association between cerebral hemorrhage and the expression of VEGF and HGF in a rat model of cerebral hemorrhage. The therapeutic potential of cerebral hemorrhage was also evaluated using targeted drugs for VEGF and HGF in the cerebral hemorrhage rat model. Behavioral and preclinical changes and the survival rates of rats were assessed after treatment with VEGF receptor (VEGFR) and HGF receptor (HGFR). The results of Tarlov scores demonstrated that movement of limbs and coordination when walking were significantly improved in moderate and severe hemorrhage lesions in the VEGFR plus HGFR‑treated group and mainly alleviated in primary hemorrhage lesions compared with rats in the single VEGFR or HGFR‑treated groups and the control group (**P<0.01). Decreasing expression levels of VEGF and HGF were observed in the neural tissue of animals treated with VEGFR plus HGFR compared with the control group (**P<0.01). These preclinical observations indicated that VEGF and HGF serve a function in the pathological injury and repair of cerebral tissue in rats with cerebral hemorrhages. The therapeutic benefits of VEGFR plus HGFR suggested that VEGFR plus HGFR may be candidate drugs for cerebral hemorrhage, and thus offer a promising treatment for clinicians and doctors.