Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus disease 2019 (version 2023) / 中华创伤杂志

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Weakly supervised multitask learning models to identify symptom onset time of unclear-onset intracerebral hemorrhage.

BACKGROUND: Approximately one-third of spontaneous intracerebral hemorrhage patients did not know the onset time and were excluded from studies about time-dependent treatments for hyperacute spontaneous intracerebral hemorrhage. AIMS: To help clinicians explore the benefit of time-dependent treatments for unclear-onset patients, we presented artificial intelligence models to identify onset time using non-contrast computed tomography (NCCT) based on weakly supervised multitask learning (WS-MTL) structure. METHODS: The patients with reliable symptom onset time (strong label) or repeat CT (weak label) were included and split into training set and test set (internal and external). The WS-MTL structure utilized strong and weak labels simultaneously to improve performance. The models included three binary classification models for classifying whether NCCT acquired within 6, 8 or 12 h for different treatments measured by area under curve, and a regression model for determining the exact onset time measured by mean absolute error. The generalizability of models was also explored in comprehensive analysis. RESULTS: A total of 4004 patients with 10,780 NCCT scans were included. The performance of WS-MTL classification model showed high accuracy, and that of regression model was satisfactory in ≤6 h subgroup. In comprehensive analysis, the WS-MTL showed better performance for larger hematomas and thinner scans. And the performance improved effectively as training amounts increasing and could be improved steadily through retraining. CONCLUSIONS: The WS-MTL models showed good performance and generalizability. Considering the large number of unclear-onset spontaneous intracerebral hemorrhage patients, it may be worth to integrate the WS-MTL model into clinical practice to identify the onset time.

Pulmonary complications and respiratory management in neurocritical care: a narrative review / 中华医学杂志(英文版)

Neurocritical care (NCC) is not only generally guided by principles of general intensive care, but also directed by specific goals and methods. This review summarizes the common pulmonary diseases and pathophysiology affecting NCC patients and the progress made in strategies of respiratory support in NCC. This review highlights the possible interactions and pathways that have been revealed between neurological injuries and respiratory diseases, including the catecholamine pathway, systemic inflammatory reactions, adrenergic hypersensitivity, and dopaminergic signaling. Pulmonary complications of neurocritical patients include pneumonia, neurological pulmonary edema, and respiratory distress. Specific aspects of respiratory management include prioritizing the protection of the brain, and the goal of respiratory management is to avoid inappropriate blood gas composition levels and intracranial hypertension. Compared with the traditional mode of protective mechanical ventilation with low tidal volume (Vt), high positive end-expiratory pressure (PEEP), and recruitment maneuvers, low PEEP might yield a potential benefit in closing and protecting the lung tissue. Multimodal neuromonitoring can ensure the safety of respiratory maneuvers in clinical and scientific practice. Future studies are required to develop guidelines for respiratory management in NCC.

The Patterns of Morphological Change During Intracerebral Hemorrhage Expansion: A Multicenter Retrospective Cohort Study.

Objectives: Hemorrhage expansion (HE) is a common and serious condition in patients with intracerebral hemorrhage (ICH). In contrast to the volume changes, little is known about the morphological changes that occur during HE. We developed a novel method to explore the patterns of morphological change and investigate the clinical significance of this change in ICH patients. Methods: The morphological changes in the hematomas of ICH patients with available paired non-contrast CT data were described in quantitative terms, including the diameters of each hematoma in three dimensions, the longitudinal axis type, the surface regularity (SR) index, the length and direction changes of the diameters, and the distance and direction of movement of the center of the hematoma. The patterns were explored by descriptive analysis and difference analysis in subgroups. We also established a prognostic nomogram model for poor outcomes in ICH patients using both morphological changes and clinical parameters. Results: A total of 1,094 eligible patients from four medical centers met the inclusion criteria. In 266 (24.3%) cases, the hematomas enlarged; the median absolute increase in volume was 14.0 [interquartile range (IQR), 17.9] mL. The initial hematomas tended to have a more irregular shape, reflected by a larger surface regularity index, than the developed hematomas. In subtentorial and deep supratentorial hematomas, the center moved in the direction of gravity. The distance of center movement and the length changes of the diameters were small, with median values of less than 4 mm. The most common longitudinal axis type was anterior-posterior (64.7%), and the axis type did not change between initial and repeat imaging in most patients (95.2%). A prognostic nomogram model including lateral expansion, a parameter of morphological change, showed good performance in predicting poor clinical outcomes in ICH patients. Conclusions: The present study provides a morphological perspective on HE using a novel automatic approach. We identified certain patterns of morphological change in HE, and we believe that some morphological change parameters could help physicians predict the prognosis of ICH patients.

A literature review on adverse outcomes resulting from lack of pharmaconutrients in critically-ill neurological patients / 中华临床营养杂志

Pharmaconutrients refer to macronutrients,micronutrients,microecologics,and nucleotides.Informed by large randomized clinical trials,people have become increasingly prudent in using pharmaconutrients.Critically-ill neurological patients are intensive care patients who have neurological impairment,and therefore command extra caution in using pharmaconutrients.This article reviews the latest studies on the use of pharmaconutrients in this group of patients.

Exosome extracted from hAMSCspromotes neurological function recovery after traumatic brain injury in rats / 基础医学与临床

Objective To investigate the therapeutic effect of exosomes extracted from human adipose-derived mesenchymal stem cells(hAMSCs) on traumatic brain injury (TBI) and its possible mechanism.Methods Mesenchymal stem cells(MSCs) were isolated from healthy human adipose tissue and the exosomes were extracted by ultrafiltration.Rats were divided into four groups: sham group, PBS control group, MSCs treatment group and exosomes treatment group.24 h After TBI, the treatment group was locally injected along the lesion area, 30 μL of PBS, 2×105 MSC, 25 μg protein of exosomes respectively, the total volume was 30 μL.We performed the Modified Neurological Severity Score(mNSS) and the forelimb Foot-Fault Test in all rats before injury and at 1, 3, 7, 10, 13, 16, 21 and 30 days after TBI.The rats were sacrificed at 3 and 7 days after TBI respectively,total RNA was extracted from rat brain tissue.The expression of TNF-α and IL-1β were detected by quantitative PCR.The rats were also killed at 30 days after TBI for testing the neuronal apoptosis in lesion area by tunel-neun double imm-unofluorescence.Results Exosomes treatment significantly promotes the recovery of neurological deficits caused by TBI,and the therapeutic effect is similar to MSCs, its possible mechanism may be the inhibition of the acute inflammation and the reducing of the neurons apoptosis after TBI.Conclusions Exosomes extracted from human adipose-derived mesenchymal stem cellshas promoted neurological functionrecovery after traumatic brain injury, which will provide a new and safer TBI treatment for clinical practice.

Progress in neural stem cells therapy for traumatic brain injury / 基础医学与临床

The neural stem cells (NSCs) can migrate into the injured area and differentiate into neurons or oligodendrocytes.Endogenous neurogenesis may potentially be harnessed as a putative therapy for neural injury.But the complex micro-environment due to TBI will be one of the biggest challenges for endogenous NSCs to perform neural regenerations.Exogenous NSCs have been shown to be able to survive in host tissues and regulate microenvironment via paracrine effects.Thus, transplantation of NSCs to assist neural regeneration has become an attractive option.Recently, rapid advances in the stem cell biology have raised appealing possibilities of replacing damaged or lost neural cells by transplantation of in vitro-expanded stem cells and/or their neuronal progeny.

Walking ability and cognitive function changes in normal pressure hydrocephalus patients after cerebrospinal fluid tap test / 中华神经科杂志

Objective To explore the walking ability and cognitive function changes in normal pressure hydrocephalus patients after cerebrospinal fluid ( CSF ) tap test for helping clinicians choose evaluation time and methods.Methods Twenty-seven patients with probable normal pressure hydrocephalus in Peking Union Medical College Hospital from 2013 to 2014 were included.All patients were evaluated using Minimum Mental State Examination, the Montreal Cognitive Assessment, Ability of Daily Life, and Idiopathic Normal Pressure Grade Scale, underwent 1.5 T head MRI scan and had ventriculo-peritoneal shunt after informerd consent.A lumbar tap with removal of 30 ml of CSF was performed in all patients.Evaluations included the 10 m walking time and steps, Trail Making Test A, number code and Stroop test.Those tests were performed 1 day before and 4, 8, 24, 72 hours after CSF tap test.The walking test and neuropsychological test results were compared between those before and after the CSF tap test.Correlation analysis was conducted between the normal pressure hydrocephalus featured MRI characters and CSF tap test responses including Evan′s index, callosum corpus angle, mismatch between narrowed high-convexity and medial subarachnoid spaces and enlarged Sylvian fissure associated with ventriculomegaly . Results Compared with 0 h walking time (23.56(14.00) s), the 10 m walking time on the 8 hours and 24 hours after CSF tap test, which were 19.41 ( 9.00 ) s and 19.67 ( 11.00 ) s respectively, were significantly improved ( Z values in Wilcoxon signed ranks test were -3.416 and -3.443 respectively,both P<0.01).There were no statistically significant differences on every evaluation time point.The neuropsychological tests changings were significant on 24 hours and 72 hours.Compared with 0 h neuropsychological test z scale (-10.28(21.60)), the z scale on the 24 hours and 72 hours after CSF tap test, which were -6.29 (26.72), -3.37(36.15)respectively, were significantly improved (Z values in Wilcoxon signed ranks test were -3.506,-2.701 respectively, both P<0.01).The Evan′s index, callosum corpus and the feature of mismatch between narrowed high-convexity and medial subarachnoid spaces and enlarged Sylvian fissure were not statistically correlated with the response of CSF tap test.Conclusions Walking ability in normal pressure hydrocephalus patients was improved after the CSF tap test.The Evan′s index, callosum corpus and the feature of mismatch between narrowed high-convexity and medial subarachnoid spaces and enlarged Sylvian fissure might not be correlated with the response of CSF tap test.

Pyrimethamine sensitizes pituitary adenomas cells to temozolomide through cathepsin B-dependent and caspase-dependent apoptotic pathways.

Invasive pituitary adenomas (PAs) are generally refractory to conventional therapy and salvage treatment with temozolomide (TMZ). In addition to antiprotozoan effects, pyrimethamine (PYR) has recently shown its strong antitumor activity as an antineoplastic agent or in combination with TMZ in metastatic melanoma cells. In this study, the effects of TMZ, PYR or TMZ/PYR combination on rat/mouse PA cell lines αT3-1, GH3, MMQ and ATt-20 as well as GH3 xenograft tumor model were evaluated. TMZ/PYR combination synergistically inhibited proliferation, invasion and induced apoptosis of these PA cell lines in vitro. Strikingly, combination treatment with TMZ and PYR produced synergistic antitumor activity and enhanced the survival rate of GH3 xenograft tumor models without increasing systemic side effects. In addition, TMZ/PYR induced cell cycle arrest, increased DNA damage, upregulated the expression of cathepsin B, BAX, cleaved PARP and phosphorylated histone H2AX as well as elevated caspase3/7, 8 and 9 activities. The decreased expression of Bcl-2, MMP-2 and MMP-9 alone with cytochrome c release from mitochondria into the cytosol was also observed in the TMZ/PYR combination group. The increase in cell apoptosis due to combination with PYR was rescued by leucovorin. These data suggest that PYR may enhance the efficacy of TMZ via triggering both cathepsin B-dependent and caspase-dependent apoptotic pathways. Therefore, combination of PYR and TMZ may provide a novel regimen for invasive PAs refractory to standard therapy and TMZ.

Comparison of Three Procedures in the Establishment of Rat Models of Focal Cerebral Ischemia / 中国实验动物学报

@#Objective To compare and evaluate the efficacy of three operating procedures to produce permanent rat models of cerebral ischemia, including mortality, neurological evaluation score, infarction volume of ischemia and time consumed in the operation. Methods The rats were randomly divided into three groups. Group 1: The common carotid artery (CCA) and external carotid artery (ECA) were ligated during the operation and ICA was clipped temporarily by artery clamp. Group 2: The CCA and ECA were ligated and the superior thyroid artery and pterygopalatine artery were exposed but not ligated. Silk suture was utilized to hang the internal carotid artery (ICA). Plastic suture was inserted into ICA and stepped over the initiation point of pterygopalatine artery under microscopic observation. Group 3: The CCA and ECA were ligated and ICA was hanged with a silk suture, and the pterygopalatine artery was not exposed, but during the period of inserting plastic suture, the proximal part of the suture was pressed to make the suture's round distal end elevated, and then pass the initial point of pterygopalatine artery. Mortality, neurological score, volume of ischemic infarction and operation time consumed of the three groups were compared after the operation. Results The procedure to prepare the model was most efficient in the group 3, taking only 17.5 min to complete, significantly less than that in the group 1 (50 min) and group 2 (40 min), (P<0.05), and with a lower mortality and more steady neurological evaluation score and infarction volume. Conclusion The use of the third operating method can shorten the operation time and improve the efficacy of operation. Using this method, more consistent and repetitive focal cerebral ischemia models can be produced effectively, and meet the demands of clinical trials.

Recent Advances in Research on Methodology of Bone Marrow Mesenchymal Stem Cell Transplant for Ischemic Stroke / 国际脑血管病杂志

The current therapeutic strategies for ischemic stroke are more limited. In the field of biotherapy bone marrow mesenchymal stem cell(BMSC) is a seed cell with the most potential. Synthesizing the advances in methodology of preclinical studies, this article mainly reviews the types of BMSC, time window for cell transplantation, approaches of cell transplantation, tracing technique in vivo after cell transplantation, and treatment effectiveness evaluation.

Effect of transplanted human bone marrow mesenchymal stem cells on behavioral changes of cerebral ischemic rats / 基础医学与临床

Objective Investigate the behaviors of cerebral ischemic rats after treatment with bone marrow mesenchymal stem cells(BMSCs).Methods Bone marrow was collected and BMSCs were separated and cultivated.Twenty-four adult male Sprague-Dawley rats were performed transient(2 hours) middle cerebral arterial occlusion(MCAO) and then divided into treated group(n=12) and control group(n=12).All rats received corresponding behavioral training before surgery,15 ?L hBMSCs(2?1010cells/L) and D-hanks(15 ?L) were injected into the brain cortex after 24 h of MCAO.Morris water maze test,NSS,Rotarod test and adhesive-removal test were performed serially and cyclically from the 4th day after transplantation.Results Since the 8th day after transplantation,the mean escape time and the mean swimming distance of treated group significantly are shorter than control's in Morris water maze test(P

Effects of superparamagnetic iron oxide on proliferation and neural differentiation of human mesenchymal stem cells / 基础医学与临床

Objective To label Flk-1+CD31-CD34-human mesenchymal stem cells (hMSCs) with superparamagnetic iron oxide (SPIO) and to evaluate the effect of SPIO on proliferation and neural differentiation of labeled cells. Methods hMSCs were incubated with SPIO (50 mg/L) and PLL (1.5 mg/L) overnight(12～18 hours). Both labeled and unlabeled cells went through growth curve test,Trypan blue staining and flow cytometer to evaluate the effects of SPIO on cell proliferation,cell viability and surface markers. Immunofluorescence assay was conducted for neuron and neuroglia specific cell surface markers after neural induction protocols were used. Results Cell viability of the two groups were both more than 90% for 7 days. There was no significant difference in cell viability and growth curve test between two groups. The results of flow cytometer showed that both labeled and unlabeled cells expressed CD44, CD105 and Flk-1 markers, while CD31 and CD34 were negative. After neural induction, the statistical analysis of A value for all the markers showed no significant difference between the two groups.Conclusion SPIO, as MRI cellular contrast, is safe and efficient.

The treatment of neural system diseases with adult stem cells——A potential field of translational medicine / 基础医学与临床

Neural system diseases are the significant burden threatening life quality of human beings. The investigation of stem cells especially the adult stem cells improved the related basic and clinical research of biological therapy and highlighted a prpspective future. The transplantation of adult stem cells maybe an effective method to treat neural system diseases. So the collaboration between the basic and clinical research will be strenthened to serve patients. Translational medicine is a potential field in which the basic medicine and clinical medicine and linked.

Application of MRI and iron oxide particle labeling in stem cell therapyof brain ischemic rats / 基础医学与临床

Objective To explore the value of MRI and iron oxide particle labeling in stem cell therapy of stroke model. Methods Nine rats with middle cerebral artery occlusion were randomly selected and underwent Neurological Severity Scoring(NSS), MRI and pathological examination. The results of the 3 evaluation criteria were correlated. Bone marrow stromal cells were labeled with superparamagnetic iron oxide particles. Eighteen models were screened and divided into 3 groups based on different transplantation sites. MRI was performed at different time points. The MR appearance of labeled stem cell transplantation sites was observed. The relative infarct volume of the models in three groups were recorded and compared. Results Significant correlations among the NSS, MRI and pathological examination were found. Different MR sequences could depict local transplanted labeled stem cells and gradient echo sequence was the most sensitive method, while the T2WI showed its advantage of better temporal resolution. MR images showed the morphological changes of transplanted stem cells. The change of the relative infarct volume showed no significant differences among the three groups. Conclusion MRI is an ideal tool to evaluate the rat stroke model. MRI together with iron oxide particle labeling technique helps to in vivo track and monitor the transplanted stem cells.