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.

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

Oncolytic virotherapy is a promising therapeutic approach treating tumors, where oncolytic viruses (OVs) can selectively infect and lyse tumor cells through replication, while also triggering long-lasting anti-tumor immune responses. Vaccinia virus (VV) has emerged as a leading candidate for use as an OV due to its broad cytophilicity and robust capacity to express exogenous genes. Consequently, oncolytic vaccinia virus (OVV) has entered clinical trials. This review provides an overview of the key strategies used in the development of OVV, summarizes the findings from clinical trials, and addresses the challenges that must be overcome in the advancement of OVV-based therapies. Furthermore, it explores potential future strategies for enhancing the development and clinical application of OVV, intending to improve tumor treatment outcomes. The review aims to facilitate the further development and clinical adoption of OVV, thereby advancing tumor therapies.
Vaccinia virus/physiology* ; Humans ; Oncolytic Virotherapy/methods* ; Oncolytic Viruses/physiology* ; Neoplasms/therapy* ; Animals

ObjectiveTo investigate the incidence rate of primary liver cancer （PLC） and the progression of liver fibrosis in chronic hepatitis B （CHB） patients with low-level viremia （LLV） （HBV DNA<2 000 IU/mL but ≥20 IU/mL） after treatment adjustment， and to provide more robust evidence for clinical practice. MethodsA retrospective analysis was performed for the clinical data of LLV patients who initially received nucleos（t）ide analogue （NAs） for at least 48 weeks at the Fifth Medical Center of PLA General Hospital from August 2007 to April 2017 and subsequently underwent NAs adjustment due to LLV， and according to the virologic response after 48 weeks of treatment adjustment， the patients were divided into LLV group and complete virological response （CVR） group （HBV DNA<20 IU/mL）. The patients were followed up once every 3‍ ‍—‍ ‍6 months till the primary endpoint event of PLC or October 2024. The incidence rate of PLC and the progression of liver fibrosis were observed， and the progression of liver fibrosis was defined as an increase of ≥1 grade in fibrosis-4 （FIB-4） index. 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 continuous data with skewed distribution between two groups； the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to calculate the cumulative incidence rate of PLC， and the Log-rank test was used for comparison between groups； the Cox regression analysis was used to investigate the risk factors for PLC， and the Logistic regression analysis was used to investigate the influencing factors for the progression of liver fibrosis. ResultsA total of 307 patients were enrolled， with a mean age of 50.0 years， and the male patients accounted for 80.5%. After 48 weeks of treatment with the adjusted NAs regimen， 254 patients （82.7%） achieved CVR， and 53 patients （17.3%） still had LLV. For the LLV group， the incidence rate of PLC was 30.2% and the rate of liver fibrosis progression was 22.6%， while for the CVR group， the incidence rate of PLC was only 13.4%， and the rate of liver fibrosis progression was 7.5%. The multivariate regression analyses showed that LLV was an independent risk factor for the onset of PLC （hazard ratio=2.623， 95% confidence interval ［CI］： 1.315‍ ‍—‍ ‍5.234， P=0.006） and the progression of liver fibrosis （odds ratio=3.213， 95%CI： 1.385‍ ‍—‍ ‍7.455， P=0.007）. ConclusionActive adjustment of treatment is needed immediately after the diagnosis of LLV to improve CVR， and if LLV persists after treatment adjustment， it is necessary to enhance the monitoring of liver fibrosis progression and PLC， so as to facilitate early diagnosis and treatment.

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 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 evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

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.