Objective: To investigate the aberrant alterations of microRNAs ( miRNAs) in exosomes derived from bone marrow stromal cells ( BMSCs) in the bone marrow supernatants of patients with acute myeloid leukemia (AML) and their impact on the prognosis of AML patients . Methods: Bone marrow supernatant samples were col- lected from three AML patients and three healthy donors . Exosomes were isolated using a commercial kit , identif- ying the morphology and marker expression , and subjected to miRNA sequencing to determine differentially ex- pressed miRNAs (DE-miRNAs) . The DE-miRNAs were then intersected with the exosomal miRNA expression pro- files of primary AML cells (GSE64029) to exclude AML cell - derived signals and to identify BMSC-derived DE - miRNAs . Subsequently , candidate miRNAs were identified through Cox regression and Lasso regression analyses based on data from The Cancer Genome Atlas (TCGA) . A prognostic risk model for AML was constructed , and pa- tients were stratified into high-risk and low-risk groups according to the median risk score . The prognostic value and clinical relevance of the model were further validated . Finally , the target genes of the candidate miRNAs were pre- dicted , followed by pathway enrichment analysis , construction of key regulatory networks , and correlation analysis between the expression levels of key miRNAs and their corresponding target genes . Results: Isolated exosomes ex- hibited a typical cup-shaped morphology with intact structures with particle size of 30 - 150 nm , and expressed exo- somal markers CD63 , ALIX , and TSG101 . miRNA sequencing identified 103 DE-miRNAs in AML patients com- pared with healthy donors; after intersection with the GSE64029 dataset , 83 BMSC-derived DE-miRNAs were re- tained . Among these , five candidate miRNAs ( miR-25-3p , miR-532-5p , miR-194-5p , miR-10a-5p , and miR- 20a-5p) were used to construct the prognostic model . Kaplan-Meier survival analysis demonstrated significantly lon- ger overall survival in the low-risk group compared with the high-risk group (P < 0. 05) . The areas under the ROC curve for the training/validation cohorts were 0. 80/0. 74 , 0. 80/0. 78 , and 0. 79/0. 64 at 1 , 2 , and 3 years , re- spectively . The prognostic model was significantly associated with risk stratification , patient age , and FAB classifi- cation (P < 0. 05) . KEGG pathway enrichment revealed that target genes of the candidate miRNAs were closely linked to cancer-related signaling pathways , including hepatocellular carcinoma , breast cancer , and non-small cell lung cancer. Correlation analysis indicated that the candidate miRNAs were significantly associated with key genes such as HIF1A , CREB1 , PIK3CA , IGF1R , PIK3R1 , TIAM1 , CRK , and PTEN (P < 0. 05) . Conclusion AML patients exhibit distinct miRNA expression profiles in BMSC-derived exosomes . A five-miRNA signature ( miR-25 - 3p , miR-532-5p , miR-194-5p , miR-10a-5p , and miR-20a-5p) demonstrates robust prognostic performance , sup- porting its potential clinical utility in risk stratification and outcome prediction for AML.

Abstract Early rehabilitation activity is an important way to improve functional impairment in stroke patients. However, there are no clear standards and opinions on the optimal start time, dosage and frequency of early rehabilitation activity. It is generally believed that early rehabilitation activity should start at 24 to 48 hours after stroke, and individual programs should be developed according to the assessment of stroke type, severity of disease, tolerance degree and other factors. This review searches domestic and international literature related to early rehabilitation activity and summarizes the start time, dose, frequency and content of early rehabilitation activity, as well as the cognition and attitude of medical workers towards it, so as to provide insights into studies and clinical applications of early rehabilitation activity.

Metabolic associated fatty liver disease(MAFLD)is currently the most common liver disease around the world.MAFLD may easily progress to the adverse outcomes such as hepatitis,liver fibrosis,and liver cirrhosis,and it is often accompanied by comorbidities such as diabetes,hypertension,hyperlipidemia,hyperuricemia,and cardiovascular and cerebrovascular diseases.Etiological treatment is the cornerstone of MAFLD treatment,and due to the complexity and adverse outcome of MAFLD,it is of great significance to explore the pathogenesis of MAFLD and develop effective prevention and treatment regimens and drugs.This article reviews the pathogenesis of MAFLD from the aspects of genetic factors,improper diet and oxidative stress,spleen-stomach damp-heat and insulin resistance,damp-heat and pathogenic Qi,organic acid metabolism,and intestinal microecology.

BACKGROUND: Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment. Our previous clinical trial demonstrated that berberine (BBR) hydrochloride might reduce the recurrence and canceration of colorectal adenoma (CRA). The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer (CRC). METHODS: We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial, and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction. We further performed ApcMin/+ animal intervention tests, RNA sequencing, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: The abundance of fecal Veillonella parvula ( V . parvula ) decreased significantly after BBR administration ( P = 0.0016) and increased through the development from CRA to CRC. Patients with CRC with a higher V. parvula abundance had worse tumor staging and a higher lymph node metastasis rate. The intestinal immune pathway of Immunoglobulin A production was activated, and the expression of TNFSF13B (Tumor necrosis factor superfamily 13b, encoding B lymphocyte stimulator [BLyS]), the representative gene of this pathway, and the genes encoding its receptors (interleukin-10 and transforming growth factor beta) were significantly upregulated. Animal experiments revealed that V. parvula promoted colorectal carcinogenesis and increased BLyS levels, while BBR reversed this effect. CONCLUSION: BBR might inhibit V. parvula and further weaken the immunomodulatory effect of B cells induced by V. parvula , thereby blocking the development of colorectal tumors. TRIAL REGISTRAION ClinicalTrials.gov, No. NCT02226185.
Animals ; Humans ; Berberine/therapeutic use* ; Carcinogenesis ; Veillonella ; Colorectal Neoplasms/genetics* ; Tumor Microenvironment

Objective:Using the classical concept analysis method of Avant & Walker, this paper made an in-depth analysis of the concept of childbirth trauma, obtained its operational definition, and provided a reference for clinical practice.Methods:We systematically searched CNKI, VIP, Wanfang, SinoMed, Web of Science, PubMed, and Embase, and the retrieval period was from the establishment of the database to August 10, 2022. We analyzed and defined childbirth trauma by Avant & Walker's classical concept analysis.Results:A total of 34 articles were included. The defining attributes of childbirth trauma were identified as persistent psychological trauma, lack of social support, loss of control, impaired dignity, and poor interaction with care providers. The antecedents could be discussed from demographic factors and disease history, obstetric nurses and midwives, and delivery environment. Consequences included affected women's physiology, behavior, and psychology.Conclusions:Birth trauma has brought lasting negative consequences to women's lives and families. Medical staff should recognize its severity, identify birth trauma in clinical practice with the help of the concept of birth trauma and operational definition, find it early, and effectively prevent it.

Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide, but the molecular basis underlying its development remains unclear. An accumulating body of evidence supports gasdermin D (GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases. However, there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis. In this work, we investigated the role of GSDMD-mediated pyroptosis in silicosis. Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression. Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica. Measurement of interleukin-1β release, lactic dehydrogenase activity, and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages. Additionally, we verified that both canonical (caspase-1-mediated) and non-canonical (caspase-4/5/11-mediated) signaling pathways mediated silica-induced pyroptosis activation, in vivo and in vitro. Notably, Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes, which highlighted the pivotal role of pyroptosis in this disease. Taken together, our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.

Objective:To explore the mediating effect of self-control between smartphone addiction and academic procrastination in medical undergraduates.Methods:A total of 640 medical college undergraduates were selected by convenient sampling method. The self-designed general information questionnaire, smartphone addiction proneness scale (SAPS), brief self-control scale (BSCS) and procrastination assessment scale-students (PASS) were conducted among the students. SPSS 25.0 was used for descriptive statistical analysis, independent sample t test, one-way ANOVA and Pearson correlation analysis. Results:Correlation analysis showed that PASS scores were positively correlated with SAPS scores ( r=0.29, P<0.01), and negatively corrected with BSCS scores ( r=-0.26, P<0.01); the SAPS scores were negatively corrected with BSCS scores ( r=-0.33, P<0.01). Mediating effect analysis showed that the mediating role of self-control between smartphone addiction and academic procrastination were significant (effect size=0.13, 95%CI=0.03-0.26), and the mediating effect accounted for 38.24%. Conclusion:Self-control played partial mediating effect between smartphone addiction and academic procrastination in medical undergraduates. In order to improve the current situation of medical undergraduate's academic procrastination, medical college educators can intervene from the perspective of smartphone addiction and self-control.

The coronavirus disease 2019 (COVID-19) has caused global public health and economic crises. Thus, new therapeutic strategies and effective vaccines are urgently needed to cope with this severe pandemic. The development of a broadly neutralizing antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the attractive treatment strategies for COVID-19. Currently, the receptor-binding domain (RBD) of the spike (S) protein is the main target of neutralizing antibodies when SARS-CoV-2 enters human cells through an interaction between the S protein and the angiotensin-converting enzyme 2 expressed on various human cells. A single monoclonal antibody (mAb) treatment is prone to selective pressure due to increased possibility of targeted epitope mutation, leading to viral escape. In addition, the antibody-dependent enhancement effect is a potential risk of enhancing the viral infection. These risks can be reduced using multiple mAbs that target nonoverlapping epitopes. Thus, a cocktail therapy combining two or more antibodies that recognize different regions of the viral surface may be the most effective therapeutic strategy.
Antibodies, Monoclonal/therapeutic use* ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Humans ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus

Objective To investigate the influence of two different mechanical ventilation modes of bi-level positive airway pressure ventilation(BIPAP)and synchronized intermittent ventilation (SIMV)on the respiratory function and clinical curative effect in children patients with severe hand foot and mouth disease(HFMD)complicating neurogenic pulmonary edema.Methods Thirty children patients with severe HFMD complicating neurogenic pulmonary edema receiving mechanical ventilation were divided into the SIMV group (control group)and BIPAP group (experimental group).The lung protective ventilation strategy was applied in both groups.After 30 min use of SIMV and positive end expiratory pressure (PEEP)ventilation,the experimental group changed to use the BIPAP ventilation mode,while the control group still used the initial parameters.The airway peak pressure,alveolar plat-form (Pplat)pressure,lung compliance,pH value,arterial blood CO2 partial pressure (PaCO2 )and oxygenation index (PaO2/FiO2 )at 0 h (baseline value),24,48,72 h after mechanical ventilation were monitored.Besides,the duration of mechanical ventila-tion,28 d mortality rate and the length of ICU stay were observed.Results Thirty children patients smoothly spent their acute re-spiratory failure period.One case in each group during the later period of treatment was transferred to the other hospital for contin-uous therapy.Among them the transferred case in the control group finally died due to give up treatment.The rest 28 cases all were cured and discharged from hospital.The 28 d mortality rates in the two groups were 6.67% and 0% respectively,with no statistical difference (P >0.05).Compared with the control group,the airway peak pressure,Pplat and PaCO2 after mechanical ventilation for 24,48,72 h in the experimental group were significantly decreased(P <0.05);the lung compliance and PaO2/ FiO2 improvement was significantly higher than that in the control group(P <0.05);meanwhile the duration of mechanical ventilation and the length of ICU stay in the experimental group were shorter than those in the control group (P <0.05).Conclusion The BIPAP mode used in the mechanical ventilation therapy of the children patients with severe HFMD complicating neurogenic pulmonary edema can pro-vide better effective ventilation,improve oxygenation and respiratory function,and shorten the duration of mechanical ventilation.

The traditional approach to accessing healthcare information restricts the further development of healthcare services,thus unable to meet the growing needs of individual healthcare.The flexible sensor technology has emerged along with the development of new materials,machinery and manufacturing technology.As a result,textiles,accessories,human skin and even internal body organs can be integrated with various sensors.The popularization of flexible sensors provides new methods for monitoring health,improving therapeutics,investigating disease status and building the human-machine in-terface.Through a systematic investigation of literature,this paper reviews the applications of flexible sensors in health-care,discusses the key technologies,and introduces the common materials and manufacturing technology.