Objective: To identify the mimicking autoantibodies using papain-enhanced erythrocyte agglutination in a case of repeated red blood cell transfusion refractoriness, aiming to explore the immune hematological methods for identifying mimicking alloantibodies, autoantibodies and alloantibodies, and to develop a safe and effective blood transfusion strategy based on the results. Methods: ABO, RhD and RhEeCc blood groups were detected using routine blood group serological method. The unexpected antibodies in plasma were screened and identified, followed by identification using a two-step papain-treated indirect antiglobulin test (enzyme-IAT). The cause of transfusion refractoriness of red blood cells was analyzed and summarized, and the prognosis was followed up. Results: The patient's blood type was type A, CCDee. The direct antiglobulin test (DAT) was positive. Unexpected antibody screening and identification using saline tube method, polybrene method, IAT were negative, and the release fluid (acid release) IAT identification was negative. Mimicking anti-e antibodies in plasma was identified by enzyme-ITA. The cause of red blood cell transfusion refractoriness in patients was autoimmune hemolysis caused by mimicking anti-e antibodies. After choosing to avoid antibodies corresponding to antigen-positive red blood cells, the patient's hemoglobin (Hb) increase value is in line with theoretical expectations, indicating effective red blood cell transfusion. Conclusion: Mimicking antibodies can cause immune destruction of red blood cells by non-specific binding to their own red blood cells and specific binding to red blood cells, resulting in red blood cell transfusion refractoriness.

Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

During long-duration manned space missions, the complex and extreme space environment exerts significant impacts on astronauts' physiological, psychological, and cognitive functions, thereby posing direct risks to mission safety and operational efficiency. As a key bridge between the brain and external devices, brain-computer interface (BCI) technology enables precise acquisition and interpretation of neural signals, offering a novel paradigm for human-machine collaboration in manned spaceflight. Non-invasive BCI technology shows broad application prospects across astronaut selection, mission training, in-orbit task execution, and post-mission rehabilitation. During mission preparation, multimodal signal assessment and neurofeedback training based on BCI can effectively enhance cognitive performance and psychological resilience. During mission execution, BCI can provide real-time monitoring of physiological and psychological states and enable intention-based device control, thereby improving operational efficiency and safety. In the post-mission rehabilitation phase, non-invasive BCI combined with neuromodulation may improve emotional and cognitive functions, support motor and cognitive recovery, and contribute to long-term health management. However, the application of BCI in space still faces challenges, including insufficient signal robustness, limited system adaptability, and suboptimal data processing efficiency. Looking forward, integrating multimodal physiological sensors with deep learning algorithms to achieve accurate monitoring and individualized intervention, and combining BCI with virtual reality and robotics to develop intelligent human-machine collaboration models, will provide more efficient support for space missions.
Brain-Computer Interfaces ; Humans ; Space Flight ; Astronauts/psychology* ; Neurofeedback ; Cognition ; Electroencephalography ; Man-Machine Systems

Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative. Isovalerylspiramycin I (ISP I) as a major component of carrimycin applied to upper respiratory infections, was first found to possess anti-fibrotic potential. The present study aims to evaluate the functions and mechanisms of ISP I in protecting against liver fibrosis. According to our results, ISP I not only reduced the expressions of fibrogenic markers in LX-2 cells but also appeared great protective effects on liver injury and liver fibrosis in bile duct ligation (BDL) rats and carbon tetrachloride (CCl₄) mice. We proved that nucleotide-binding protein 2 (NUBP2) was the direct target of ISP I. ISP I through targeting NUBP2, increased the amount of vascular non-inflammatory molecule-1 (VNN1) on the cell membrane, which will inhibit oxidative stress and fibrosis. Simultaneously, the original carrimycin's protective effect on liver damage and fibrosis was verified. Therefore, our study provides potential agents for patients with liver fibrosis-related diseases, and the clear mechanism supports wide application in the clinic.

ObjectiveTo investigate the features of liver histopathological damage in patients with indeterminate phase of chronic HBV infection， as well as the timing for initiating antiviral therapy in such patients. MethodsA retrospective screening was performed for the patients with chronic HBV infection who were hospitalized in The Fifth Medical Center of Chinese PLA General Hospital and underwent liver biopsy from March 2018 to April 2022， among whom the patients who met the criteria for indeterminate phase defined in Chinese guidelines for chronic hepatitis B prevention and treatment （2022 edition） were enrolled， and their clinical data were collected. Liver histopathological stage was determined using the Scheuer scoring system， with stages 0 — 4 for inflammation grade （G） and stages 0 — 4 for fibrosis degree （S）， and the patients were divided into groups based on the presence of significant necroinflammation （≥G2） and significant liver fibrosis （≥S2）. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A Spearman’s rank correlation analysis was used to investigate the correlation between liver histopathology and clinical factors， and the Logistic regression model was used to identify the independent influencing factors for significant necroinflammation and liver fibrosis. ResultsA total of 271 patients with indeterminate phase of chronic HBV infection were enrolled， among whom 61 （22.5%） had significant necroinflammation （≥G2） and 124 （45.8%） had significant liver fibrosis （≥S2）. The Logistic regression analysis showed that alanine aminotransferase ≥30 U/L （for male patients） or ≥19 U/L （for female patients） （odds ratio ［OR］=2.69， 95% confidence interval ［CI］： 1.39 — 5.21， P=0.003）， HBV DNA ≥2 000 IU/mL （OR=2.75， 95%CI： 1.38 — 5.48， P=0.004）， and liver stiffness measurement （LSM） ≥6.0 kPa （OR=4.57， 95%CI： 2.17 — 9.62， P<0.001） were independent risk factors for significant inflammation. HBV DNA ≥2 000 IU/mL （OR=1.82， 95%CI： 1.01 — 3.32， P=0.049） and LSM ≥6.0 kPa （OR=2.06， 95%CI： 1.23 — 3.43， P=0.006） were independent influencing factors for significant liver fibrosis. ConclusionAmong the patients with indeterminate phase of chronic HBV infection， a substantial proportion of patients have significant liver histopathological damage. Antiviral therapy should be initiated in a timely manner for patients with high-risk factors.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative.Isovalerylspiramycin Ⅰ(ISP Ⅰ)as a major component of carrimycin applied to upper respiratory infections,was first found to possess anti-fibrotic potential.The present study aims to evaluate the functions and mechanisms of ISP Ⅰ in protecting against liver fibrosis.According to our results,ISP Ⅰ not only reduced the expressions of fibrogenic markers in LX-2 cells but also appeared great protective effects on liver injury and liver fibrosis in bile duct ligation(BDL)rats and carbon tetrachloride(CCl4)mice.We proved that nucleotide-binding protein 2(NUBP2)was the direct target of ISP Ⅰ.ISP Ⅰ through targeting NUBP2,increased the amount of vascular non-inflammatory molecule-1(VNN1)on the cell membrane,which will inhibit oxidative stress and fibrosis.Simultaneously,the original carri-mycin's protective effect on liver damage and fibrosis was verified.Therefore,our study provides po-tential agents for patients with liver fibrosis-related diseases,and the clear mechanism supports wide application in the clinic.

Objective:To investigate the characteristics, influencing factors, consequences, coping strategies, and preventive measures of workplace violence in medical consortiums.Methods:Medical professionals from a specialized hospital in South China and its consortium members (2 primary-level, 1 secondary-level, and 1 tertiary-level hospitals) were surveyed in December 2022 and July 2023. Quantitative research included 1013 participants, while qualitative research involved 35 participants. Workplace violence was assessed using the "National Case Study Tool for Workplace Violence in Healthcare Institutions-Survey Questionnaire", with qualitative analysis conducted through semi-structured interviews. Inter-group comparisons employed chi-square tests or Fisher's exact probability test, with logistic regression models for bivariate analysis.Results:The overall incidence rates of violence, psychological violence, and physical violence in this medical consortium were 31.7% (321/1, 013) , 30.6% (310/1, 013) , and 3.3% (33/1, 013) , respectively. Specifically, the overall violence rates in Level 1, Level 2, and Level 3 hospitals were 22.7% (41/181) , 27.4% (43/157) , and 35.1% (237/675) . The physical violence rates were 1.1% (2/181) , 10.2% (16/157) , and 2.2% (15/675) , respectively. The psychological violence rates stood at 22.7% (41/181) , 24.8% (39/157) , and 34.1% (230/675) . The total violence in tertiary hospitals was significantly higher than that in tertiary hospitals ( F=10.10, P=0.002) , and the incidence of psychological violence in tertiary hospitals was significantly higher than that in tertiary hospitals ( Flevel 1 vs level 3=8.61, P=0.003; Flevel 2 vs level 3=4.96, P=0.026) , incidence of verbal insults ( Flevel 1 vs level 3=8.25, P=0.004; Flevel 2 vs level 3=6.36, P= 0.012) was significantly higher than that of level 1 and level 2 hospitals. The incidence of physical violence in secondary hospitals was significantly higher than that of other two-level hospitals ( P<0.001) . Compared with other types of violence, the incidence of verbal insults is highest in hospitals at all levels. Higher anxiety about violence was a risk factor for psychological violence in hospitals at all levels ( Flevel1 hospital=15.44, P=0.004; Flevel2 hospital=22.87, P<0.001; Flevel3 hospital=84.12, P<0.001) . Health workers in all three levels of hospitals has a high level of approval of existing workplace violence interventions. The main causes of workplace violence were poor communication between doctors and patients (13.2%) , service attitude problems (12.5%) and patient illness (16.9%) . Conclusion:Workplace violence remains prevalent within this medical consortium. Targeted measures should be implemented based on hospital size, functions, and patient demographics.

Objective To investigate the sputum metabolic profiles of patients with occupational coal workers' pneumoconiosis (CWP) by an untargeted metabolomics method, and to identify relevant differential metabolic pathways and potential biomarkers. Methods A total of 12 male patients with stage Ⅰ CWP were selected as the CWP group, and 16 healthy male individuals were selected as the control group, using a judgmental sampling method. Sputum metabolites of individuals in both groups were detected to perform non-targeted metabolomic analysis using the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Differential metabolites (DMs) and their pathways were screened using principal component analysis, partial least squares discriminant analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Potential biomarkers were analyzed and identified via the receiver operating characteristic curve (ROC). Results There were apparent metabolic alterations observed in sputum of CWP patients compared with healthy controls. In the positive ion mode, a total of 42 DMs were identified in sputum from CWP patients, including 19 downregulated and 23 upregulated metabolites. In the negative ion mode, a total of 25 DMs were identified in sputum from CWP patients, including 16 downregulated and 9 upregulated metabolites. KEGG enrichment analysis of sputum from CWP patients showed that seven DMs pathways were enriched in ABC transporters, histidine metabolism, phenylalanine metabolism, arachidonic acid metabolism, linoleic acid metabolism, purine metabolism, and oxidative phosphorylation, involving 26 DMs. ROC analysis indicated that 16(R)-hydroxyarachidonic acid, pyrophosphate, and 2-hydroxyphenylacetate of these 26 DMs may serve as potential biomarkers for CWP. Conclusion Sputum metabolomic profiles were altered in CWP patients compared with healthy controls. The potential biomarkers of CWP prevention and treatment are 16(R)-hydroxyarachidonic acid, pyrophosphate, and 2-hydroxyphenylacetate.

OBJECTIVE: To investigate the effect of relaxing needling at the contracted sites of meridian-muscle regions in the patients with post-stroke shoulder-hand syndrome (SHS) at acute stage. METHODS: Eighty patients with post-stroke SHS at acute stage were randomized into an observation group (40 cases, 1 case dropped out) and a control group (40 cases, 1 case was eliminated). In the control group, the routine medication, basic rehabilitation training, and hyperbaric oxygen therapy were administered. In the observation group, besides the treatment as the control group, relaxing needling was delivered at the contracted sites of meridian-muscle regions. These contracted sites were distributed along three yin meridians of hand and three yang meridians of hand on the affected upper limbs. The intervention was given once daily, 5 times a week and for 4 weeks. Before and after treatment, the scores of visual analogue scale (VAS) for pain, edema degree, modified Barthel index (MBI), and Fugl-Meyer assessment (FMA) for motor function, and the integrated electromyography (iEMG) of surface electromyogram (sEMG) were observed in the two groups. The curative effect was evaluated after treatment and in follow-up of 2 months after treatment in the two groups. RESULTS: After treatment, VAS scores and the scores of edema degree were reduced when compared with those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than those in the control group (P<0.05). MBI and FMA scores increased after treatment compared with those before treatment in the two groups (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05) after treatment. The iEMG values of the biceps brachii, triceps brachii, and wrist extensors were elevated after treatment in comparison with those before treatment (P<0.05) in the two groups, and the values in the observation group were larger than those in the control group after treatment (P<0.05). The total clinical effective rate in the observation group was 92.3% (36/39), which was better than that of the control group (74.4%, 29/39, P<0.05) after treatment; and that of the observation group was 97.4% (38/39), which was better than 82.1% (32/39) in the control group (P<0.05) in follow-up. CONCLUSION Relaxing needling at the contracted sites of meridian-muscle regions in treatment of post-stroke SHS at acute stage can attenuate the symptoms such as upper limb pain, swelling and spasm, improve motor function and the activity of daily living of patients.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Therapy ; Aged ; Meridians ; Stroke/complications* ; Reflex Sympathetic Dystrophy/etiology* ; Adult ; Acupuncture Points