Objective: To investigate the epidemiological characteristics, outcome patterns, and management strategies for blood donors with a positive direct antiglobulin test (DAT). Methods: A retrospective analysis was conducted on donation data from 808 386 donors from 2013 to 2023, focusing on those whose blood was discarded due to DAT positivity. Follow-up was performed on 125 DAT-positive donors, and 98 blood samples were collected. The samples were re-tested for DAT, DAT typing (IgG/C3d), and unexpected antibody screening using both the tube method and the microcolumn gel method. Results: Epidemiological characteristics: Retrospective data revealed 147 DAT-positive blood donors, yielding a positivity rate of 1/5 500. The DAT positivity rate using the tube method was 0.118‰ (49/416 893), lower than that of the microcolumn gel method at 0.25‰ (98/391 493). Among DAT-positive individuals, 44.2% (65/147) exhibited agglutination intensity<2+. Outcome analysis: The proportion of donors with positive DAT test results that converted to negative was 54.1% (53/98), with a conversion interval ranging from 8 to 117 months (mean 49.9 months). All donors in the negative conversion group had a previous DAT intensity<2+, whereas 95.6% (43/45) of the non-negative conversion group had intensity ≥2+ (P<0.001). Unexpected antibodies (anti-E, anti-M, etc.) were detected in 18 cases. Methodological differences: Review of results revealed 35 cases positive by both the DAT tube assay and microcolumn gel method. An additional 10 cases were positive by only one method: 5 were positive only by the tube assay, and 5 were positive only by the microcolumn gel method. Clinical validation: Among 14 DAT-positive donors who became negative and donated blood again, the clinical infusion efficacy of red blood cell products could be assessed in 10 cases, with 9 cases demonstrating effective infusion. Conclusion: Some DAT-positive blood donors may naturally convert to negative status, with the intensity of previous test results potentially serving as a key predictive factor for conversion. It is recommended to employ a combined approach of tube-based and microcolumn gel-based methods for retesting, concurrently screening for irregular antibodies. A tentative tiered management strategy is proposed: individuals with DAT intensity <2+ should be deferred for 12 months before retesting, while those with ≥2+ intensity should be permanently deferred.

Diabetic Peripheral Neuropathy （DPN） is one of the most common and harmful complications of type 2 diabetes. DPN's pathogenesis include high blood sugar-induced oxidative stress， inflammation， and mitochondrial dysfunction. These factors are combined to damage nerve fibers， leading to sensory issues， pain， and numbness. Through a coordinated effect， these factors trigger nerve fiber damage and lead to sensory abnormalities， pain and numbness in limbs， and other symptoms， seriously restricting patients' activities of daily living and mobility. Recent research highlights that cellular senescence plays a critical role in DPN. Cellular senescence is manifested by the loss of cell proliferation ability， and further aggravates nerve damage via oxidative stress， mitochondrial dysfunction， autophagy impairment， inflammatory reaction， and other mechanisms， accelerating DPN occurrence and progression. In terms of medical treatment， current methods focus on blood sugar control， pain relief medicine， and microcirculation improvement， while no therapy has been developed based on cellular senescence. In contrast， traditional Chinese medicine （TCM） shows a unique advantage in DPN prevention and treatment via cellular senescence modulation. TCM emphasizes a holistic approach， as well as syndrome differentiation and treatment， effective in anti-aging and nerve damage repair. Recent studies show that TCM active ingredients， including puerarin， ginsenosides， and berberine， can reduce inflammation， oxidative stress， and apoptosis via signaling pathway regulation， thereby slowing cellular senescence to alleviate nerve damage. Furthermore， TCM compounds such as Buyang Huanwutang， Taohong Siwutang， and Huangqi Guizhi Wuwutang exert synergistic effects on cellular senescence-related pathways to improve nerve health and reduce DPN clinical symptoms. Therefore， this paper reviews the literature related to the interaction between cellular senescence and DPN from the perspective of cellular senescence， summarizing the mechanism of DPN and TCM intervention strategies.

The deficiency of fingers due to various reasons leads to a certain degree of loss of full or part hand functions. Physical and mental health of patients are seriously affected, and patients have varying degrees of reduced quality of life. Prosthesis fingers play an important role in completing the body shape and enhancing patients’ self-confidence and self-esteem. However, how to make prosthesis fingers perform coordinated movements and restore complete functions is a crucial problem that urgently needs to be solved. This paper reviews the methods of brain-computer interface controlled fine finger movements and elaborates on the origin, current situation, and advancements of the development of this technology, laying a foundation for subsequent research, with the expectation of helping patients solve the problems arising from the insufficiency or absence of finger functions.

ObjectiveTo investigate the effects of Chaihu and Longgu Mulitang （CLMT） on hippocampal neural damage in the mouse model of depression via the extracellular signal-regulated protein kinase （ERK）/cAMP-response element-binding protein （CREB） signaling pathway. MethodsSeventy-eight male C57BL/6 mice were randomly allocated into normal control， model， low/medium/high-dose （2.89， 5.78， and 11.56 g·kg^-1， respectively） CLMT， and paroxetine （10 mg·kg^-1） groups. A depression model was established by chronic unpredictable mild stress （CUMS） combined with social isolation. Behavioral tests were carried out to evaluate depressive-like behaviors. Hematoxylin-eosin staining and Nissl staining were performed to assess hippocampal morphology and neuronal damage. Immunofluorescence was employed to detect glial fibrillary acidic protein （GFAP） and ionized calcium-binding adapter molecule 1 （Iba1）. Real-time PCR was employed to measure the mRNA levels of ERK and CREB. Western blot was employed to determine the expression of ERK/CREB pathway proteins and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. Molecular Operating Environment （MOE） software was used for molecular docking to evaluate the interactions between CLMT components and target proteins. ResultsCompared with the normal control group， the model group showed decreased sucrose preference （P0.01）， increased tail-suspension immobility time （P0.01）， decreased activity in the central region of the open field test （P0.01）， and decreased activity in the middle and open-arm region of the elevated plus maze test （P0.01）. The hippocampal area in the model group showed wrinkled cells and a reduction in the number of cells， neurons with reduced sizes and Nissl bodies， enhanced fluorescence intensity of GFAP and Iba1 （P0.01）， and down-regulated expression of phosphorylated （p）-ERK， p-CREB， and BDNF （P0.05， P0.01） and mRNA levels of ERK and CREB （P0.01）. Compared with the model group， the CLMT group showed increased body weight （P0.05， P0.01）， restored cell morphology， with only a small number of ruptured cells， normal neuronal structure and morphology with obvious nuclei and abundant Nissl bodies， weakened fluorescence intensity of GFAP and Iba1 （P0.05， P0.01）， up-regulated mRNA levels of ERK and CREB （P0.05， P0.01） and protein levels of phosphorylated （p）-ERK， p-CREB， and BDNF in the hippocampal tissue （P0.05， P0.01）. The results of molecular docking indicated that nine active ingredients in CLMT had good binding affinity with ERK and CREB. ConclusionCLMT may ameliorate the hippocampal nerve injury in the mouse model of depression by regulating the ERK/CREB pathway.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Tubal ciliary movement is one of the essential transport mechanisms for female fertility, playing a key role in facilitating oocyte pickup and transporting the fertilized ovum. This movement is mediated by multiciliated cells and regulated by specific proteins and hormones that modulate ciliary number, length, polarity, beat frequency, and amplitude to ensure proper function. Genetic mutations, inflammatory stimuli, and hormonal fluctuations can impair ciliary activity or induce ciliary apoptosis, leading to ciliary dysfunction. Disorders of tubal ciliary movement are frequently observed in primary ciliary dyskinesia, pelvic inflammatory disease, polycystic ovary syndrome, and endometriosis, conditions commonly associated with female infertility. These disorders manifest as structural abnormalities of cilia, disrupted polarity, shortened ciliary length, reduced ciliary count, and decreased beat frequency and amplitude. Understanding the role of tubal ciliary movement in female infertility-related diseases, through immunohistochemistry and ultrastructural analysis, helps clarify underlying infertility mechanisms. Identifying abnormal inflammatory factors, hormonal environments, and gene expression, combined with advanced techniques for measuring ciliary protein and beat frequency, may offer novel clinical targets for early prevention and treatment of female infertility.
Humans ; Female ; Infertility, Female/etiology* ; Cilia/physiology* ; Polycystic Ovary Syndrome/physiopathology* ; Fallopian Tubes/physiopathology* ; Endometriosis/complications* ; Pelvic Inflammatory Disease/complications*

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Objective·To investigate the expression of serpin family E member 1(SERPINE1)in gastric cancer and its potential mechanisms in promoting gastric cancer.Methods·Pan-cancer analysis of SERPINE1 was performed by using the TIMER2.0 online website,and the differences in the expression of SERPINE1 in samples with different tumor stages of gastric cancer were analysed by the clinical data of gastric cancer from The Cancer Genome Atlas(TCGA)database.Survival curves were plotted.Quantitative real-time PCR(qRT-PCR)was used to detect mRNA expression in paired samples of clinical gastric cancer tissues.The small interfering RNA(siRNA)transfection technique was used to knock down the expression of SERPINE1 in MGC-803 and SGC-7901 gastric cancer cell lines,and the migration and invasive abilities of gastric cancer cells were investigated by Transwell and invasion chamber experiments.The effects of SERPINE1 knockdown on the angiogenesis of gastric cancer cells were further explored by the migration assay of human umbilical vein endothelial cells(HUVEC)and tubule formation assay of HUVECs.The Gene Expression Omnibus(GEO)dataset was used for differential gene analysis in high and low expression groups based on the median value of SERPINE1 expression.The differentially expressed genes were further analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and Gene Set Enrichment Analysis(GSEA).qRT-PCR was performed to verify the expression levels of key genes related to epithelial-mesenchymal transition(EMT)and angiogenesis.Results·Bioinformatics analysis showed that SERPINE1 was highly overexpressed in a variety of primary tumour tissues,including gastric cancer.SERPINE1 gene expression increased with increasing tumour stage(P<0.001),and increased expression of SERPINE1 was associated with poor prognosis of gastric cancer(P<0.001).qRT-PCR results showed that SERPINE1 was significantly highly expressed in gastric cancer tissues(P=0.038).After knocking down SERPINE1,gastric cancer cell lines MGC-803 and SGC-7901 cells had decreased migration and invasion(P<0.05).Gastric cancer culture supernatants from the SERPINE1-knockdown gastric cancer cell line reduced angiogenesis in HUVECs(P<0.05).Differential genes in gastric cancer patients in the SERPINE1 high-expression group in the GEO database were enriched in cancer-related pathways such as focal adhesion,extracellular matrix receptor interaction,and angiogenesis-related pathways like angiogenesis and the vascular endothelial growth factor(VEGF)signalling pathway.The expression of SERPINE1 was negatively correlated with cadherin 1(CDH1),and positively correlated with other key genes related to EMT and angiogenesis.Moreover,the expression levels of key genes related to EMT and angiogenesis detected by qRT-PCR in SERPINE1 knockdown gastric cancer cell lines(P<0.05),were consistent with the correlation analysis results mentioned above.Conclusion·SERPINE1 expression is elevated in gastric cancer tissues,which could regulate the expression levels of key genes related to EMT and angiogenesis to promote the migration,invasion and angiogenesis of gastric cancer cells.

Objective:This study aimed to explore the molecular mechanisms of the maladaptation of H3N2 influenza virus in chicken embryos, provide a theoretical basis for the restoration of H3N2 influenza vaccine production in chicken embryos.Methods:Samples of respiratory secretions from patients with influenza-like symptoms (Influenza-like Illness, ILI) caused by H3N2 influenza virus were inoculated into chicken embryos and Madin-Darby Canine Kidney cells (MDCK), respectively. After isolating the virus, hemagglutination experiments were conducted to detect hemagglutination titers and hemagglutination inhibition experiments were used to compare antigenic differences; further, whole-genome sequencing of H3N2 influenza virus was performed using second-generation high-throughput gene sequencing (Next Generation High-Throughput Gene Sequencing, NGS), and key amino acid sites of mutations were identified through sequence alignment; combined with sialic acid receptor binding experiments, the differences in the binding of wild-type and mutant receptor binding sites (RBS) to sialic acid receptors were compared; finally, molecular docking and molecular dynamics simulation method were used to explore the specific molecular mechanisms of how mutation sites affect the differences in the affinity of the RBS pocket for sialic acid receptors.Results:The hemagglutination assay result indicated that both chicken embryos and MDCK cells could isolate the influenza virus, and the hemagglutination inhibition test showed that no antigenic differences were produced in the isolated strains. NGS analysis revealed that the H3N2 virus underwent an F195Y mutation in the (RBS) region of the hemagglutinin (HA) protein after adaptation through chicken embryo passages. Receptor-binding experiments demonstrated that the F195Y mutation enhanced the virus′s binding ability to α2, 3-linked sialic acid glycan (Neu5Acα2-3Galβ1-4GlcNAcβ-PAA, 3′SLN), while the mutation did not affect the affinity of the RBS pocket for α2, 6-linked sialic acid glycan (Neu5Acα2-6Galβ1-4GlcNAcβ-PAA, 6′SLN). Molecular docking and molecular dynamics simulation result indicate that the F195Y mutation, by replacing a hydrophobic amino acid with a hydrophilic one, leads to a significant decrease in the structure of the RBS pocket, enhancing the binding stability of the H3N2 influenza virus with α2, 3-sln. This is specifically manifested by an increase in binding time and an increase in the number of hydrogen bonds at the RBS site with the receptor. Furthermore, the F195Y mutation does not alter the binding of the virus to other receptors.Conclusions:The F195Y mutation in the RBS pocket of H3N2 influenza virus is a key site affecting the viral chicken embryo inadaptability.

Objective:To systematically compares the medial plantar venous flap (MPVF) and the lateral toe flap (LTF) reconstruction of digit-pulp defect, aiming to establish whether there exist significant differences between the 2 flaps in flap survival rate, two-point discrimination (TPD), score of Vancouver Scar Scale (VSS) and score of digit-pulp defect reconstruction evaluation.Methods:With a prospective cohort design, this study enrolled 36 patients who were admitted in Department of Hand Surgery, Longgang Eighth People's Hospital of Shenzhen for digit-pulp defects with bone or tendon exposure between January 2024 and September 2024. According to the random grouping method, participants were divided into 2 groups. The MPVF group comprised 18 patients (21 digits) of 13 males (15 digits) and 5 females (6 digits), aged 13-58 (mean 44±12) years. The MPVF group included 9 left and 12 right digits, with distribution as follows: 2 thumbs, 5 index fingers, 7 middle fingers, 5 ring fingers and 2 little fingers. The soft tissue defect area ranged from 2.0 cm × 1.0 cm to 9.2 cm × 3.3 cm (mean 6.69 cm 2± 6.69 cm 2). Flap dimensions ranged from 2.1 cm×1.1 cm to 9.5 cm×3.5 cm (mean 7.54 cm 2±7.22 cm 2). Donor sites were closed primarily or by full-thickness skin grafts harvested from the leg. The LTF group included 18 patients (21 digits) of 15 males (17 digits) and 3 females (4 digits), aged 22-62 (mean 41±12) years. The affected digits in LTF group comprised 12 left and 9 right digits, with a distribution of: 3 thumbs, 9 index fingers, 5 middle fingers, 2 ring fingers and 2 little fingers. The area of soft tissue defect ranges from 1.4 cm × 1.0 cm to 3.9 cm × 1.8 cm (mean 3.93 cm 2± 1.80 cm 2). Flap dimensions ranged from 1.5 cm×1.2 cm to 4.0 cm×1.9 cm (mean 4.52 cm 2±1.89 cm 2). Donor sites were closed primarily, or by full-thickness skin grafts harvested through extension of proximal wound extension or from calf for defect coverage. Patients were contacted for postoperative follow-up by telephone or WeChat to arrange a visit of outpatient clinic or a home visit by surgeon. Statistical analysis was conducted to compare the 2 groups regarding: gender, age and flap dimensions, flap survival rate at 2 weeks after surgery and TPD of flaps, VSS scores, and digit-pulp defect reconstruction evaluation scale scores at 4 months and 6 months postoperatively. P<0.05 indicates a statistically significant difference. Results:The comparative analysis revealed no statistically significant differences between 2 groups in baseline characteristics: gender distribution ( χ2=0.53, P=0.47), mean age ( t=0.75, P=0.46), flap dimensions ( t=1.86, P=0.08), confirming a demographic and surgical parameter equivalence in subsequent outcome comparisons ( P>0.05). All flaps survived at 2 weeks after surgery. All skin grafts at donor sites demonstrated complete viability with uneventful primary wound healing. At 4 months after surgey, the TPD in the MPVF group were 14.71 mm±1.90 mm and 7.81 mm±1.78 mm, respectively, compared to 14.48 mm±1.57 mm and 7.67 mm±1.39 mm in the LTF group at 6 months after surgery. The VSS scores were 1.67±1.11 and 1.29±0.72 for MPVF versus 1.86±1.15 and 1.38±0.81 for LTF at corresponding time points. The digit-pulp defects reconstruction evaluation scale scores showed 88.43±2.62 and 91.43±3.59 for MPVF versus 88.19±2.70 and 91.19±3.50 for LTF. Statistical analysis revealed no significant differences (all P>0.05) at 2 postoperative time points. Conclusion:The MPVF demonstrated non-inferior clinical efficacy to the LTF in reconstruction of digit-pulp defects, with comparable outcomes in flap survival rate at 2 weeks, and in TPD, VSS scores, digit-pulp defect reconstruction evaluation scale scores at 4 months and at 6 month after surgey.