ObjectiveTo evaluate the clinical benefits of early right median nerve electrical stimulation on coma patients following craniocerebral trauma. MethodsCraniocerebral trauma patients with up to two weeks of coma in the years 2005-2011 were involved in the study and were randomly divided into control group (received routine management ) and treatment group (routine management plus right median nerve electrical stimulation).The treatment lasted for a period of more than two weeks.The clinical efficacy of the right median nerve electric stimulation and the conscious status of the patients within six months after craniocerebral trauma were observed.ResultsA total of 456 patients were enrolled in the study,of whom 437 patients completed the treatment course,including 221 patients in the treatment group and 216 in the control group.There was no complication related to electric stimulation during the treatment.Cerebral blood flow (CBF) imaging and brain stem evoked potential (BEP) examination demonstrated significant improvement in the treatment group.A total of 386 patients were followed up for six months postoperatively,which showed that there were 122 patients with regained consciousness,46 in minimally conscious state and 36 in vegetative state in the treatment group (204 patients) and there were 84 patients with regained consciousness,40 in minimally conscious state and 58 in vegetative state in the control group ( 182 patients).The patients in the treatment group showed a higher ratio of regained consciousness and a lower ratio of vegetative state compared with the control group,but the ratio of minimally conscious state showed no statistical difference between two groups. ConclusionsRight median nerve electrical stimulation is a suitable coma awaking means at early stage after craniocerebral trauma.

Objective:To explore the predictive value of HACOR score [heart rate (H), acidosis (A), consciousness (C), oxygenation (O), and respiratory rate (R)] on the clinical outcome of non-invasive positive pressure ventilation in patients with pulmonary encephalopathy due to chronic obstructive pulmonary disease (COPD).Methods:A prospective study was conducted. The patients with COPD combined with pulmonary encephalopathy who were admitted to Henan Provincial People's Hospital from January 1, 2017 to June 1, 2021 and initially received non-invasive positive pressure ventilation were enrolled. Besides non-invasive positive pressure ventilation, standard medical treatments were delivered to these patients according to guidelines. The need for endotracheal intubation was judged as failure of non-invasive ventilation treatment. Early failure was defined as the need for endotracheal intubation within 48 hours of treatment, and late failure was defined as the need for endotracheal intubation 48 hours and later. The HACOR score at different time points after non-invasive ventilation, the length of intensive care unit (ICU) stay, the total length of hospital stay, and the clinical outcome were recorded. The above indexes of patients with non-invasive ventilation were compared between successful and failed groups. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive effect of HACOR score on the failure of non-invasive positive pressure ventilation in the treatment of COPD with pulmonary encephalopathy.Results:A total of 630 patients were evaluated, and 51 patients were enrolled, including 42 males (82.35%) and 9 females (17.65%), with a median age of 70.0 (62.0, 78.0) years old. Among the 51 patients, 36 patients (70.59%) were successfully treated with non-invasive ventilation and discharged from the hospital eventually, and 15 patients (29.41%) failed and switched to invasive ventilation, of which 10 patients (19.61%) were defined early failure, 5 patients (9.80%) were late failure. The length of ICU and the total length of hospital stay of the non-invasive ventilation successful group were significantly longer than those of the non-invasive ventilation failure group [length of ICU stay (days): 13.0 (10.0, 16.0) vs. 5.0 (3.0, 8.0), total length of hospital stay (days): 23.0 (12.0, 28.0) vs. 12.0 (9.0, 15.0), both P < 0.01]. The HACOR score of patients at 1-2 hours in the non-invasive ventilation failure group was significantly higher than that in the successful group [10.47 (6.00, 16.00) vs. 6.00 (3.25, 8.00), P < 0.05]. However, there was no significant difference in HACOR score before non-invasive ventilation and at 3-6 hours between the two groups. The ROC curve showed that the area under the ROC curve (AUC) of 1-2 hour HACOR score after non-invasive ventilation for predicting non-invasive ventilation failure in COPD patients with pulmonary encephalopathy was 0.686, and the 95% confidence interval (95% CI) was 0.504-0.868. When the best cut-off value was 10.50, the sensitivity was 60.03%, the specificity was 86.10%, positive predictive value was 91.23%, and negative predictive value was 47.21%. Conclusions:Non-invasive positive pressure ventilation could prevent 70.59% of COPD patients with pulmonary encephalopathy from intubation. HACOR score was valuable to predict non-invasive positive pressure ventilation failure in pulmonary encephalopathy patients due to COPD.

Cabozantinib, mainly targeting cMet and vascular endothelial growth factor receptor 2, is the second-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, the lower response rate and resistance limit its enduring clinical benefit. In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Mechanically, the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT, extracellular signal-regulated protein kinases, mTOR, and common downstream signal molecules of receptor tyrosine kinases; decreased cyclin D1 expression; and induced cell cycle arrest. Meanwhile, rapamycin enhanced the inhibitory effects of cabozantinib on the migration and tubule formation of human umbilical vascular endothelial cells and human growth factor-induced invasion of cMet inhibitor-resistant HCC cells under hypoxia condition. These effects were further validated in xenograft models. In conclusion, our findings uncover a potential combination therapy of cabozantinib and rapamycin to combat cabozantinib-resistant HCC.
Anilides/pharmacology* ; Animals ; Carcinoma, Hepatocellular/drug therapy* ; Cell Line, Tumor ; Cell Proliferation ; Endothelial Cells/metabolism* ; Humans ; Liver Neoplasms/drug therapy* ; Pyridines/pharmacology* ; Sirolimus/pharmacology* ; Xenograft Model Antitumor Assays