Neurological diseases are a major health concern, and brain injury is a typical pathological process in various neurological disorders. Different biomarkers in the blood or the cerebrospinal fluid are associated with specific physiological and pathological processes. They are vital in identifying, diagnosing, and treating brain injuries. In this review, we described biomarkers for neuronal cell body injury (neuron-specific enolase, ubiquitin C-terminal hydrolase-L1, αII-spectrin), axonal injury (neurofilament proteins, tau), astrocyte injury (S100β, glial fibrillary acidic protein), demyelination (myelin basic protein), autoantibodies, and other emerging biomarkers (extracellular vesicles, microRNAs). We aimed to summarize the applications of these biomarkers and their related interests and limits in the diagnosis and prognosis for neurological diseases, including traumatic brain injury, status epilepticus, stroke, Alzheimer's disease, and infection. In addition, a reasonable outlook for brain injury biomarkers as ideal detection tools for neurological diseases is presented.
Humans ; Biomarkers/cerebrospinal fluid* ; Nervous System Diseases/diagnosis* ; Brain Injuries/metabolism* ; Phosphopyruvate Hydratase/cerebrospinal fluid* ; Glial Fibrillary Acidic Protein/blood* ; S100 Calcium Binding Protein beta Subunit/blood* ; tau Proteins/cerebrospinal fluid* ; Ubiquitin Thiolesterase/blood* ; Myelin Basic Protein/cerebrospinal fluid* ; Neurofilament Proteins/blood* ; MicroRNAs/blood* ; Brain Injuries, Traumatic/metabolism*

Recent studies have identified a missense mutation in the β1-receptor (ADRB1-A187V) that exerts a pronounced impact on human sleep, with a noted decrease in protein abundance in vivo. The administration of β-blockers is frequently associated with sleep disturbances in clinical settings. In this study, we assessed the influence of various β-blockers on sleep within mouse models. Our findings indicated that β-blockers could induce varying degrees of arousal, sleep disruption, and a decrease in REMS (rapid eye movement sleep). We examined the dose-dependent effects of metoprolol and nebivolol on both sleep and cardiac functionality in both wild-type and Adrb1-A187V mutant mice. Our data suggested that, in contrast to cardiac effects, higher doses of metoprolol are required to have noted impact on sleep. No genotype effect was observed with metoprolol in terms of sleep or cardiac function. In contrast, the mutant mice demonstrated increased sensitivity to nebivolol, which exacerbated sleep fragmentation and impeded the onset of REMS. This study is expected to provide some reference for minimizing the occurrence of sleep disorders and reducing the adverse reactions of drugs to the greatest extent.

ObjectiveTranscription factor NFE2 was observed abnormal expression in myeloproliferative neoplasm (MPN) patients. However, how NFE2 is transcriptionally regulated remains ambiguous. This study aims to explore the elements and molecular mechanisms involved in the transcriptional regulation of NFE2. MethodsActive enhancers were predicted by public NGS data and conformed experimentally via dual luciferase reporter assay. After that, PRO-seq and GRO-seq data was used to detect enhancer RNAs transcribed from these enhancers. RACE was utilized to clone the full length enhancer RNA (eRNA) transcripts, and RT-qPCR was used to measure their expression in different leukemia cell lines as well as the transcript levels during induced differentiation. Finally, to investigate the molecular function of the eRNA, overexpression and knockdown of the eRNA via lentivirus system was performed in K562 cells. ResultsWe identified three enhancers regulating NFE2 transcription, which located at -3.6k, -6.2k and +6.3k from NFE2 transcription start site (TSS) respectively. At the -3.6k enhancer, we cloned an eRNA transcript and characterized that as a lncRNA which was expressed and located in the nucleus in three types of leukemia cell lines. When this lncRNA was overexpressed, expression of NFE2 was upregulated and decreases of K562 cell proliferation and migration ability were observed. While knocking down of this lncRNA, the level of NFE2 decreases correspondingly and the proliferation ability of K562 cells increases accordingly. ConclusionWe identified an enhancer lncRNA that regulates NFE2 transcription positively and suppresses K562 cell proliferation.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Objective:To explore the behavioral intentions of pediatric nurses towards using vascular visualization devices in light of the theory of planned behavior.Methods:This was a qualitative study. From March to November 2023, 20 pediatric nurses from Peking University First Hospital were selected using purposive sampling for semi-structured interviews. The interview data were analyzed and themes were extracted using Colaizzi 7-step analysis method.Results:The behavioral intentions of pediatric nurses towards the use of vascular visualization devices could be summarized into nine themes based on the theory of planned behavior. Attitudes towards behavior included positive evaluations, negative evaluations, and unclear information. Subjective norms involved peers' attitudes as well as expectations and pressures from patients. Perceived behavioral control encompassed workload, level of knowledge, more limited equipment performance, and external resource support.Conclusions:The behavioral intentions of pediatric nurses towards the use of vascular visualization devices are influenced by their attitudes towards the behavior, subjective norms, and perceived behavioral control. Nursing managers should conduct standardized training on vascular visualization devices to enhance nurses' knowledge and skills, while also valuing the sources of various supports to create a supportive environment for the use of vascular visualization devices. This will improve the usage experience of pediatric nurses and promote the use of vascular visualization devices in pediatric nursing practice.

Objective:Clot waveform analysis (CWA) of activated partial thromboplastin time (APTT) was used to rapidly identify patients with hemophilia A (HA) and lupus anticoagulant (LA) positive, and to explore the diagnostic efficacy of APTT-CWA in HA and LA-positive patients.Methods:From July 25, 2022, to December 28, 2023, 145 patients with APTT prolongation were admitted to the First Hospital of Jilin University. This group comprised 106 males and 39 females, with an average age of (29.3±15.8) years, among whom there were 94 clinically confirmed HA cases and 51 LA-positive cases. The retrospective analysis employed the Mann-Whitney U test to compare APTT results and CWA parameters between HA patients and LA-positive individuals.CWA parameters including the first derivative of maximum reaction velocity (|min1|), the second derivative of maximum acceleration (|min2|), and maximum deceleration (|max2|) were investigated. Patients were classified based on the duration of APTT prolongation into mild (33 s53 s) groups. A comparison of APTT seconds and CWA parameters |min1|, |min2|, and |max2| was conducted for HA and LA-positive patients between each group. Furthermore, receiver operating characteristic (ROC) curves and area under the curve (AUC) were utilized to assess the diagnostic efficacy of CWA parameters and determine cut-off values. Results:The APTT results for HA and LA-positive patients were 70.2 s and 41.5 s, respectively, exhibiting a statistically significant difference ( P<0.001). CWA parameters |min1| were 1.459 %/s vs 3.868 %/s, |min2| were 0.124 %/s2 vs 0.502 %/s2, and |max2| were 0.054 %/s2 vs 0.388 %/s2in HA and LA patients, respectively ( P<0.001). In all APTT prolongation groups, the CWA parameters |min1|, |min2|and |max2| for HA were significantly lower than those for LA-positive patients ( P<0.05). CWA graph analysis revealed that the peak heights of |min1|, |min2|, and |max2| in HA were lower compared to LA patients. In the severe extension group, HA displayed significantly decreased peak values and a flatter, incomplete curve. ROC curve analysis indicated AUC values were greater than 0.8 ( P<0.01) for |min1|, |min2|, and |max2| in all APTT prolongation groups. Cut-off values for |min1|, |min2|, and |max2| were established for each prolongation group: mild (3.205 %/s, 0.423 %/s2, and 0.300 %/s2), moderate (2.884 %/s, 0.340 %/s2, 0.231 %/s2), and severe (2.209 %/s, 0.190 %/s2, 0.095 %/s2). Conclusion:When APTT was extended within the same range, there were significant differences in CWA parameters between HA patients and LA patients, ROC curve analysis demonstrated the effectiveness of CWA parameters in distinguishing HA from LA-positive patients,APTT-CWA can serve as a low-cost, efficient, and specific method for the rapid identification of hemophilia and lupus anticoagulant-positive patients.

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss.With the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption.CD301b+macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone regeneration.However,the key upstream targets of CD301b+macrophages and their potential mechanism in periodontitis remain elusive.In this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b+macrophages.We first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b+macrophages was significantly upregulated compared to CD301b-macrophages via high-throughput RNA sequencing.Moreover,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b+macrophages.The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages.The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b+macrophages as periodontitis progressed.Furthermore,the deficiency of Tim4 in mice decreased CD301b+macrophages and eventually magnified alveolar bone resorption in periodontitis.Additionally,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b+macrophages phenotype.In a word,Tim4 might regulate CD301b+macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.

Objective To evaluate the polishing finish of four different polishing tools.Methods Fifty specimens were selected from suitable zirconia and randomly divided into 5 groups with 10 specimens in each group.Group A was the negative control group;Group B was the EVE group;Group C was the SHOFU group;Group D was the Toboom group,and Group E was the NAIS group.All specimens were subjected to surface roughness measurements after each level of treatment.One specimen in each group was randomly selected after each level of treatment and put into the vacuum coater for surface gold spraying,and then put into the scanning electron microscope for surface morphology observation after vacuuming.Results Final Ra value:The negative group((1.677±0.066)μm)＞SHOFU group((0.357±0.037)μm)＞EVE group((0.248±0.051)μm)＞Toboom group((0.115±0.039)μm)and NAIS group((0.123±0.029)μm).Scanning electron microscope observation showed that the deepest and longest scratches were left on the surface of the specimen with the diamond needle,and the surface of the specimen was gradually smoothed by using the polishing kit to treat the surfacein turn.The surface of the specimens polished by NAIS group and Toboom group had the least and shallow scratches under the mirror.Conclu-sion Toboom and NAIS zirconia polishing tools provide the best polishing results.

Objective To investigate the clinical value of combined red blood cell distribution width (RDW), mean platelet volume (MPV), mean corpuscular volume (MCV) and procalcitonin (PCT) levels in the early diagnosis of acute pancreatitis (AP). Methods A total of 86 patients with AP were enrolled in AP group. and divided into mild acute pancreatitis (MAP) group (n=41), moderately severe acute pancreatitis (MSAP) group (n=27) and severe acute pancreatitis (SAP) group (n=18) based on the severity of their condition. An additional 80 healthy individuals undergoing routine physical examinations during the same period were recruited as control group. Peripheral blood levels of PCT, lipase (LIP), interleukin (IL)-17 and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA). RDW, MPV, MCV, triglyceride, lactate dehydrogenase and urea nitrogen levels were determined using a fully automated biochemical analyzer. Pearson correlation analysis was employed to assess the correlations between RDW, MPV, MCV, PCT levels and other indicators in AP patients. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the clinical value of peripheral blood RDW, MPV, MCV and PCT in the early diagnosis of AP. Results The levels of body mass index, triglyceride, lactate dehydrogenase, urea nitrogen, LIP, IL-17, TNF-α, RDW, MPV, MCV and PCT in the AP group were significantly higher than those in the control group (P < 0.05). The RDW, MPV, MCV and PCT levels were significantly higher in the MSAP and SAP groups than in the MAP group, and the RDW, MPV, MCV and PCT levels in the SAP group were significantly higher than those in the MSAP group (P < 0.05). Pearson correlation analysis revealed positive correlations between RDW, MPV, MCV as well as PCT levels and body mass index, triglyceride, lactate dehydrogenase, urea nitrogen, LIP, IL-17 as well as TNF-α levels in the AP patients (P < 0.05). ROC curve analysis indicated that the areas under the curve (AUCs) for early diagnosis of AP using peripheral blood RDW, MPV, MCV and PCT were 0.780, 0.873, 0.818 and 0.830, respectively. The AUC for combined diagnosis using these four markers was 0.972, with a specificity of 92.50% and a sensitivity of 93.02%. The combined diagnosis of RDW, MPV, MCV and PCT demonstrated superior diagnostic value compared to individual markers (Z=5.060, 3.250, 4.162, 4.272, P < 0.05). Conclusion The RDW, MPV, MCV and PCT levels were elevated in the AP patients, and their combined diagnosis of early AP was of high clinical value.

OBJECTIVE: To investigate the anti-invasion efficacy of the ethanol extract of Oldenlandia diffusa Will. (EEOD) on a three-dimensional (3D) human malignant glioma (MG) cell invasion and perfusion model based on microfluidic chip culture and the possible mechanism of action of Oldenlandia diffusa Will. (OD). METHODS: The comprehensive pharmacodynamic analysis method in this study was based on microfluidic chip 3D cell perfusion culture technology, and the action mechanism of Chinese medicine (CM) on human MG cells was investigated through network pharmacology analysis. First, the components of EEOD were analyzed by ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Then, cell viability and apoptosis were assessed to determine the optimum concentration of EEOD for invasion experiments, and two-dimensional (2D) migration and invasion abilities of U87 and U251 MG cells were evaluated using scratch wound and Transwell assays. The possible mechanism underlying the effects of EEOD on glioma was analyzed through a network pharmacology approach. RESULTS: Thirty-five compounds of EEOD were detected by UPLC-Q-TOF/MS. EEOD suppressed the viability of MG cells, promoted their apoptosis, and inhibited their migratory and invasive potentials (all P<0.05). Network pharmacology analysis showed that OD inhibited the invasion of MG cells by directly regulating MAPK and Wnt pathways through MAPK, EGFR, MYC, GSK3B, and other targets. The anti-invasion effect of OD was also found to be related to the indirect regulation of microtubule cytoskeleton organization. CONCLUSIONS ]EEOD could inhibit the invasion of human MG cells, and the anti-invasion mechanism of OD might be regulating MAPK and Wnt signaling pathways and microtubule cytoskeleton organization.