Objective To explore macrophage subpopulations in ischemic stroke (IS) by using single-cell RNA sequencing (scRNA-seq) data analysis and High-Dimensional Weighted Gene Co-Expression Network Analysis (hdWGCNA). Methods Based on single-cell sequencing data, transcriptomic information for different cell types was obtained, and macrophages were selected for subpopulation identification. hdWGCNA, cell-cell communication, and pseudotime trajectory analysis were used to explore the characteristics of macrophage subpopulations following IS. Key genes related to IS were identified using microarray data and validated for diagnostic potential through Receiver Operating Characteristic (ROC) analysis. Gene Set Enrichment Analysis (GSEA) was conducted to investigate the potential functions of these genes. Results The scRNA-seq data analysis revealed significant changes in macrophage subpopulation composition after IS. A specific macrophage subpopulation enriched in the stroke group was identified and designated as MCAO-specific macrophages (MSM). Pseudotime trajectory analysis indicated that MSM cells were in an intermediate stage of macrophage differentiation. Cell-cell communication analysis uncovered complex interactions between MSM cells and other cells, with the CCL6-CCR1 signaling axis potentially playing a crucial role in neuroinflammation. Two gene modules associated with MSM were identified via hdWGCNA, significantly enriched in pathways related to NOD-like receptors and antigen processing. By integrating differentially expressed MSM genes with conventional transcriptomic data, three IS-related hub genes were identified: Arg1, CLEC4D, and CLEC4E. Conclusion This study reveals the characteristics and functions of macrophage subpopulations following IS and identifies three hub genes with potential diagnostic value, providing novel insights into the pathological mechanisms of IS.
Macrophages/metabolism* ; Computational Biology/methods* ; Single-Cell Analysis/methods* ; Transcriptome ; Ischemic Stroke/metabolism* ; Animals ; Gene Regulatory Networks ; Gene Expression Profiling ; Humans ; Male

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVE: To compare the effects of different chest compression rates (60-140 times/min) on hemodynamic parameters, return of spontaneous circulation (ROSC), resuscitation success, and survival in a porcine model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). METHODS: Forty healthy male domestic pigs were randomly divided into five groups based on chest compression rate: 60, 80, 100, 120, and 140 times/min (n = 8). All animals underwent standard anesthesia and tracheal intubation. A catheter was inserted via the left femoral artery into the thoracic aorta to monitor aortic pressure (AOP), and another via the right external jugular vein into the right atrium to monitor right atrial pressure (RAP). In each group, animals were implanted with a stimulating electrode via the right external jugular vein to the endocardium, and ventricular fibrillation (VF) was induced by delivering alternating current stimulation, resulting in CA. After a 1-minute, manual chest compressions were performed at the assigned rate with a compression depth of 5 cm. The first defibrillation was delivered after 2 minutes of CPR. No epinephrine or other pharmacologic agents were administered during the entire resuscitation process. From 1 minute before VF induction to 10 minutes after ROSC, dynamic monitoring of AOP, coronary perfusion pressure (CPP), and partial pressure of end-tidal carbon dioxide (P_ETCO₂). Cortical ultrastructure was examined 24 hours post-ROSC using transmission electron microscopy. RESULTS: With increasing compression rates, both the total number of defibrillations and cumulative defibrillation energy significantly decreased, reaching their lowest levels in the 120 times/min group. The number of defibrillations decreased from (4.88±0.83) times in the 60 times/min group to (2.25±0.71) times in the 120 compressions/min group, and energy from (975.00±166.90)J to (450.00±141.42)J. However, both parameters increased again in the 140 times/min group [(4.75±1.04)times, (950.00±207.02)J], the differences among the groups were statistically significant (both P < 0.01). As compression frequency increased, P_ETCO₂, pre-defibrillation AOP and CPP significantly improved, peaking in the 120 times/min group [compared with the 60 times/min group, P_ETCO₂ (mmHg, 1 mmHg≈0.133 kPa): 18.69±1.98 vs. 8.67±1.30, AOP (mmHg): 95.13±7.06 vs. 71.00±6.41, CPP (mmHg): 14.88±6.92 vs. 8.57±3.42]. However, in the 140 times/min group, these values declined significantly again [P_ETCO₂, AOP, and CPP were (10.59±1.40), (72.38±11.49), and (10.36±4.57) mmHg, respectively], the differences among the groups were statistically significant (all P < 0.01). The number of animals achieving ROSC, successful resuscitation, and 24-hour survival increased with higher compression rates, reaching a peak in the 120 times/min group (compared with the 60 times/min group, ROSC: 7 vs. 2, successful resuscitation: 7 vs. 2, 24-hour survival: 7 vs.1), then decreased again in the 140 times/min group (the animals that ROSC, successfully recovered and survived for 24 hours were 3, 3, and 2, respectively). Transmission electron microscopy revealed that in the 60, 80, and 140 times/min groups, nuclear membranes in cerebral tissue were irregular and incomplete, nucleoli were indistinct, and mitochondria were swollen with reduced cristae and abnormal morphology. In contrast, the 100 times/min and 120 times/min groups exhibited significantly attenuated ultrastructural damage. CONCLUSIONS Among the tested chest compression rates of 60-140 times/min, a chest compressions frequency of 120 times/min is the most favorable hemodynamic profile and outcomes during CPR in a porcine CA model. However, due to the wide spacing between groups, further investigation is needed to determine the optimal compression rate range more precisely.
Animals ; Cardiopulmonary Resuscitation/methods* ; Swine ; Male ; Heart Arrest/therapy* ; Heart Massage/methods* ; Hemodynamics

OBJECTIVE To establish the specific chromatogram of Qianghuo Shengshi Tang(QHSS) reference sample, clarify the key quality attributes of QHSS, providing reference for the quality evaluation of QHSS reference sample. METHODS The SilGreen C18 column(4.6 mm×250 mm, 5 μm) was used. The mobile phase consisted acetonitrile and 0.2% formic acid aqueous solution. The detection wavelength was 328 nm. Established an HPLC characteristic spectrum analysis method for the reference sample of QHSS. A variety of chromatographic columns and different instruments were applied to investigate the adaptability of the system. HPLC-LTQ-Orbitrap MS was used to identify the specific peaks of the QHSS reference samples in positive ion mode. RESULTS There were 14 peaks in the specific chromatogram, which belonged to Notopterygii Rhizoma Et Radix, Angelicae Pubescentis Radix, Ligustici Rhizoma Et Radix, Chuanxiong Rhizome, Viticis Fructus, respectively. Ferulic acid(peak 3) was reference peak. A total of 22 compounds were identified by mass spectrometry, including coumarin and flavonoids. CONCLUSION The established specific chromatogram method of QHSS is simple, stable and reproducible. The material basis of QHSS reference sample is basically determined, providing a reference for the development and quality control of QHSS.

The stenosis and embolization of internal fistula vessels directly affect the clinical treatment effect of maintenance hemodialysis patients, and the study of the mechanism of internal fistula stenosis has become a research hotspot in recent years. Previous studies mainly focused on the hemodynamics and pathophysiology of blood vessel wall, and there were few studies on molecular biology and its related signaling pathways. This paper reviews the hemodynamics of the vascular pathway of internal arteriovenous fistula (AVF), the pathophysiological mechanism, molecular biology, and changes in various signaling pathways of AVF dysfunction at home and abroad, in order to provide references for the study of AVF dysfunction.

Objective:To investigate the feasibility and clinical diagnostic value of rapid arterial spin labeling (ASL) imaging in brain glioma.Methods:Patients with glioma admitted to Beijing Tiantan Hospital, Capital Medical University from May 2021 to December 2022 were prospectively enrolled. All patients received MR rapid ASL (scan time: 1 min) and conventional ASL (scan time: 4 min 30 s), where the cerebral blood flow (CBF) perfusion maps were obtained. The qualitative analysis of CBF signal intensity and quantitative analysis of average CBF values from both tumor solid and edema regions were conducted by two radiologists independently. Kappa test and intraclass correlation coefficient ( ICC) were used to analyze the consistency of qualitative and quantitative results, respectively. Results:A total of 30 patients with brain glioma were included. The 2 physicians used rapid ASL to determine low perfusion, isoperfusion, and hyperperfusion in the tumor area in 1, 6, 23 cases and 0, 5, and 25 cases, respectively; and used conventional ASL to determine low perfusion, isoperfusion, and hyperperfusion in the tumor area in 0, 9, and 21 cases, respectively. The results of qualitative analysis of rapid ASL and conventional ASL were highly consistent within and between groups ( Kappa was 0.830 and 0.850 respectively). The results of quantitative analysis of rapid ASL and conventional ASL were highly consistent within and between groups ( ICC 0.940—0.994). Conclusion:Rapid ASL with shorter scanning time could be applied in assessing tissue perfusion in brain glioma and contribute to the clinical diagnosis of gliomas.

Objective:To analyze the changes and clinical significance of homocysteine (Hcy), folate, and cardiac enzyme levels in patients with alcohol dependence and depression.Methods:A total of 102 patients with alcohol dependence and depression, who received treatment at Wenzhou Seventh People's Hospital from January 2022 to June 2023, were included in the observation group. The degree of alcohol dependence in patients in the observation group was assessed using the Michigan Alcoholism Screening Test (MAST). According to the assessment results, the patients in the observation group were divided into the following subgroups: mild alcohol dependence ( n = 33), moderate alcohol dependence ( n = 37), heavy alcohol dependence ( n = 15), and severe alcohol dependence ( n = 17). The severity of depression among patients in the observation group was assessed with the Hamilton Depression Scale (HAMD). Based on the assessment results, the patients in the observation group were divided into the following subgroups: mild depression ( n = 43), moderate depression ( n = 34), and severe depression ( n = 25). The cognitive function of patients in the observation group was assessed using the Montreal Cognitive Assessment Scale (MoCA). According to the assessment results, the patients in the observation group were divided into normal cognitive function ( n = 73) and cognitive impairment ( n = 29) subgroups. Thirty healthy volunteers from our hospital during the same period were included in the control group. The levels of Hcy, folate, and cardiac enzymes were compared among all groups. The correlations between Hcy, folate, and cardiac enzyme levels with HAMD, MoCA, and MAST scores were analyzed using the Pearson method. Results:The Hcy level in the observation group was (15.21 ± 1.99) μg/L, which was significantly higher than that in the control group [(11.38 ± 1.46) μg/L, t = -9.80, P < 0.001]. The levels of folate, lactate dehydrogenase (LDH), and creatine kinase (CK) in the observation group were (4.82 ± 1.77) μg/L, (122.69 ± 33.98) IU/L, and (87.83 ± 16.52) IU/L, respectively, which were significantly lower than those in the control group [(6.27 ± 1.35) μg/L, (150.56 ± 38.78) IU/L, (98.67 ± 20.29) IU/L, t = 4.16, 3.82, 2.99, all P < 0.05]. The Hcy levels in the mild , moderate, heavy, and severe alcohol dependence subgroups [(13.16 ± 1.23) μg/L, (15.35 ± 0.82) μg/L, (16.79 ± 1.38) μg/L, (17.63 ± 1.22) μg/L] increased sequentially, while the folate levels [(6.11 ± 1.51) μg/L, (4.95 ± 1.40) μg/L, (4.04 ± 0.99) μg/L, (2.70 ± 0.99) μg/L], LDH levels [(153.35 ± 27.47) IU/L, (123.29 ± 16.59) IU/L, (109.83 ± 14.41) IU/L, (73.24 ± 16.86) IU/L], and CK levels [(104.14 ± 12.78) IU/L, (86.48 ± 9.15) IU/L, (78.11 ± 7.85) IU/L, (67.71 ± 9.00) IU/L] decreased sequentially. These differences in Hcy, folate, LDH, and CK levels among the mild, moderate, heavy, and severe alcohol dependence subgroups were statistically significant ( F = 73.24, 26.53, 59.08, 53.86, all P < 0.001). The Hcy levels in the mild, moderate, and severe depression subgroups [(13.75 ± 1.54) μg/L, (15.46 ± 1.17) μg/L, (17.39 ± 1.31) μg/L] increased progressively, while the folate levels [(5.83 ± 1.77) μg/L, (4.67 ± 1.12) μg/L, (3.28 ± 1.26) μg/L], LDH levels [(138.09 ± 33.67) IU/L, (119.73 ± 26.39) IU/L, (100.24 ± 30.88) IU/L], and CK levels [(96.35 ± 15.24) IU/L, (86.73 ± 15.62) IU/L, (74.69 ± 9.71) IU/L] decreased progressively. The differenes in Hcy, folate , LDH, and CK levels among the four depression subgroups were statistically significant ( F = 56.57, 24.36, 12.23, 18.44, all P < 0.001). The Hcy levels in the cognitive impairment group [(17.01 ± 1.63) μg/L] was significantly higher than that in the normal cognitive function group [(14.50 ± 1.64) μg/L, t = -6.97, P < 0.001), and the folate, LDH, and CK levels in the cognitive impairment group were (3.76 ± 1.78) μg/L, (102.71 ± 31.08) IU/L, and (76.00 ± 13.37) IU/L respectively, which were significantly lower than those in the normal cognitive function group [(5.24 ± 1.58) μg/L, (130.63 ± 31.92) IU/L, (92.52 ± 15.31) IU/L, t = 4.11, 4.01, 5.09, all P < 0.001]. Hcy levels were positively correlated with HAMD and MAST scores ( r = 0.854, 0.846, both P < 0.05) and negatively correlated with MoCA scores ( r = -0.648, P < 0.001). Folate, LDH, and CK levels were negatively correlated with HAMD and MAST scores ( r = -0.644, -0.701; r = -0.551, -0.696; r = -0.505, -0.673; all P < 0.001), and they were positively correlated with MoCA scores ( r = 0.514, 0.436, 0.448, all P < 0.001). Conclusion:In patients with alcohol dependence and depression, abnormal levels of Hcy, folate, and cardiac enzymes were observed. These indicators were found to be associated with the severity of alcohol dependence, the level of depression, and cognitive function.

Objective:To summarize the best evidence for external auditory canal irrigation in patients with cerumen embolism.Methods:The clinical decisions, guidelines, systematic reviews, expert consensus, group standards, evidence summaries, and randomized controlled trials regarding external auditory canal irrigation in patients with cerumen embolism were retrieved from databases and websites such as BMJ Best Practice, UpToDate, Guidelines International Network, National Institute for Health and Clinical Excellence, Joanna Briggs Institute Evidence-Based Health Care Center Database, PubMed, Embase, China National Knowledge Infrastructure, WanFang data, and China Biology Medicine disc. The search period was from database establishment to February 15, 2023. Six researchers screened the literature, evaluated the methodological quality, and extracted and summarized the best evidence for external auditory canal irrigation in patients with cerumen embolism.Results:A total of nine articles were included, including one clinical decision, two guidelines, two systematic reviews, one group standard, and three randomized controlled trials. Sixteen pieces of evidence were summarized from six aspects of operators: pre-operation evaluation and preparation, operation process, post-operation handling, health education, and adverse reactions during operation.Conclusions:This paper summarizes the best evidence for external auditory canal irrigation in patients with cerumen embolism. Medical and nursing staff should carefully select and apply evidence based on clinical scenarios and patient's wishes.

Objective:To standardize the management of auditory hallucination symptoms in inpatients with mental illness and develop an expert consensus on the management of auditory hallucinations in hospitalized psychiatric patients.Methods:From March 2023 to July 2023, the Mental Health Committee of the Chinese Nursing Association focused on the key issues in the management of auditory hallucinations symptoms in inpatients with mental illness, based on clinical practice, using literature analysis combined with the work experience of mental health experts, and formed the first draft of the expert consensus on the management of auditory hallucinations in inpatients with mental illness (hereinafter referred to as the consensus). Through 3 rounds of expert consultation and 3 rounds of expert demonstration meeting, the draft was adjusted, revised, and improved.Results:37 experts were included in the Delphi expert consultation, 1 male and 36 females with 39-67(51.48 ± 6.61) years old. The positive coefficients of experts in 3 rounds of Delphi expert consultations were all 100%, and the degrees of expert authority were 0.924, 0.938 and 0.949, respectively. The average importance value of each item was higher than 4.00, the variation coefficient of each item was less than 0.25. The Kendall harmony coefficient of the experts were 0.179, 0.195 and 0.198, respectively (all P<0.05). There were 15, 12, 12 experts in the first, seeond, third rounds of expert demonstration meeting. Finally, a consensus was reached on the recommendation of 4 parts, included auditory hallucination assessment, management format, symptom management implementation, and precautions. Conclusions:The consensus covers all parts of the management of auditory hallucination symptoms in hospitalized patients with mental disorders, which is practical and scientific. It is helpful to guide mental health professionals to standardize the management of auditory hallucination symptoms, improve the quality of nursing and ensure the safety of patients.

BACKGROUND:Studies have shown that there are significant differences in the geometric morphology of the distal femur of different races and genders,and there are more short female patients in southern China,so the phenomenon of overhanging or insufficient coverage of imported knee prostheses often occurs during surgery. OBJECTIVE:To investigate the characteristics of distal femur bones in southern Chinese women and compare them with imported joint prostheses by simulating the three-dimensional reconstruction of the distal femur bone and matching the femoral side after osteotomy with common imported joint prostheses. METHODS:From January to December 2021,120 female volunteers underwent a CT scan of knee joints.The images were imported into Mimics 20.0 software in Dicom format for three-dimensional reconstruction and then imported into Magic 22.0 software to simulate osteotomy by posterior cruciate ligament preserved total knee arthroplasty and to conduct a matching study with a normal imported joint prosthesis. RESULTS AND CONCLUSION:(1)The functional anteroposterior dimension(fAP)of the distal femur and Persona matched prosthesis had a total overhang rate of 25%(30/120).The fAP≤47 mm group had an overhang than the other groups(P<0.05).The poor coverage rate of Triathlon prosthesis was 12.5%(15/120),and poor coverage was more likely in fAP>53 mm group than in fAP≤53 mm group(P<0.05).(2)The total poor coverage rate of femoral intercondylar width matching with Triathlon prosthesis was 27.5%(33/120).Therefore,the poor coverage rate of bone surface in the central region of the distal femur was more likely in the fAP≤47 mm group than in other groups(P<0.05).The overhang rate of Journey II was 21.6%(26/120),and the overhang rate was higher in the fAP>53 mm group than in the fAP≤53 mm group(P<0.05).(3)Journey II CR prosthesis had the largest difference with the length of the anterior mediolateral diameter of the femur,which was easy to hang out on the anterolateral side of the femoral prosthesis.The Persona CR prosthesis has the largest difference with the length of the posterior mediolateral diameter of the femur,which is easy to be poorly covered in the posterior medial part of the prosthesis.It is recommended to increase the femoral prosthesis with reduced mediolateral diameter in the fAP≤47 mm group and add wider and narrower sizes than the conventional size of intercondylar width,and optimize the anterolateral angular arc design of the femoral prosthesis to improve the matching of posterior cruciate ligament reserved knee prosthesis.