Objective: To explore the correlation between Candida albicans and the development of oral leukoplakia (OLK), and to provide a basis for improving the pathogenic mechanism of the malignant transformation of OLK. Methods: Oral microbiome data were obtained from public databases (NCBI BioProject, PRJNA788378; GEO, GSE227919), and bioinformatic methods were employed to evaluate the correlation between Candida albicans infection and OLK. Approval was obtained from the institutional Medical Ethics Committee. A tissue microarray was constructed using samples collected from an OLK clinical cohort. Hematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining were performed to analyze the relationship between the Candida albicans detection rate and clinicopathological features. Approval was obtained from the institutional Animal Ethics Committee. A mouse model was established by combining 4-nitroquinoline-1-oxide (4NQO) in drinking water with oral inoculation of Candida albicans (4NQO + Candida albicans group), while mice treated with 4NQO in drinking water and PBS served as the control group (4NQO + PBS group). The degree of epithelial dysplasia was compared between the two groups to assess the impact of Candida albicans infection on lesion progression (defined in this study as the progression from mild/moderate epithelial dysplasia to severe dysplasia/carcinoma in situ or invasive squamous cell carcinoma). Results: Bioinformatic analysis revealed that the detection rate of Candida albicans in OPMDs and OLK tissues was significantly higher than that in the healthy control group. Staining results of clinical samples demonstrated that Candida albicans colonized OLK lesions; compared with Candida albicans-negative patients, positive patients exhibited a state of high-grade progression. Animal experiments indicated that, compared with the 4NQO + PBS group, the degree of oral epithelial dysplasia in the 4NQO + Candida albicans group was significantly exacerbated, and the malignant transformation rate was higher, suggesting that Candida albicans promotes the high-grade progression of OLK. Conclusion Candida albicans exhibits a increasing trend during the malignant progression of the OLK. It aggravates the degree of epithelial dysplasia in OLK and promotes its transformation into high-grade lesions, suggesting that Candida albicans plays a crucial promoting role in the high-grade progression of OLK.

ObjectiveTo investigate the effect of mitochondrial calcium uniporter （MCU） on the cytoskeleton of pancreatic ductal epithelial cells in a mouse model of acute pancreatitis （AP） induced by caerulein （CAE）， to analyze the role of MCU in the development of AP， and to provide a theoretical basis for clinical treatment. MethodsIn the in vivo experiment， wild-type male C57BL6/J mice， aged 4 weeks， were randomly divided into control group and AP group， with 6 mice in each group. The mice in the AP group were given intraperitoneal injection of CAE to establish a model of AP， and those in the control group were given intraperitoneal injection of an equal volume of normal saline. Serum and pancreatic tissue samples were collected after 24 hours of modeling. HE staining was used to observe pancreatic histopathological changes； Western Blot was used to measure the expression levels of MCU， glutathione peroxidase 4 （GPX4）， and acyl-CoA synthetase long chain family member 4 （ASCL4）； kits were used to measure the serum level of amylase. In the in vitro experiment， the human pancreatic ductal epithelial cell line HPDE6-C7 was co-cultured with CAE for 24 hours to establish an in vitro AP model， and the cells were divided into control group， CAE group， RR （an MCU activity inhibitor） group， CAE+RR group， Fer-1 （an ferroptosis inhibitor） group， CAE+Fer-1 group， Erastin （an ferroptosis inducer） group， and CAE+Erastin group. CCK-8 assay was used to observe the influence of different agents on cell viability； Western Blot was used to measure the expression levels of MCU， GPX4， and ASCL4； immunofluorescence assay was used to measure reactive oxygen species （ROS）， actin cytoskeleton， and monolayer permeability； kits were used to measure the concentrations of malondialdehyde （MDA）， glutathione （GSH）， Fe²⁺， and total iron. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for comparison between two groups. ResultsIn the in vivo experiment， compared with the control group， the AP group had significant increases in pancreatic histopathological score， the serum level of amylase， and the expression levels of MCU and ASCL4， as well as a significant reduction in the expression of GPX4 （all P<0.05）. In the in vitro experiment， compared with the control group， the CAE group had significant increases in the expression levels of MCU and ASCL4， a significant reduction in the expression of GPX4， and significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability， as well as a significant reduction in the concentration of GSH （all P<0.05）， with the presence of actin cytoskeleton disruption. Compared with the CAE group， the CAE+RR group had a significant increase in the expression level of GPX4， a significant reduction in the expression level of ASCL4， and significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Fer-1 group had significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Erastin group had significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant reduction in the concentration of GSH （all P<0.05）， with aggravation of actin cytoskeleton disruption. ConclusionDuring the onset of AP， MCU mediates oxidative stress-induced ferroptosis and leads to the disruption of the pancreatic ductal epithelial barrier， which may be one of the possible pathogeneses of AP.

Objective To investigate dynamic changes in myocardial protein phosphorylation during the acute phase of myocardial infarction (MI) in mice. Methods Six 8-week-old C57BL/6J mice were randomly assigned to MI model (n＝3) or sham-operated control (n＝3) groups. Cardiac tissues were harvested 72 hours post-intervention for proteomic analysis. Phosphorylation modifications were systematically characterized using liquid chromatography-mass spectrometry (LC-MS). Bioinformatics analyses included differential phosphorylation screening, functional enrichment, hierarchical clustering, and protein-protein interaction network. Results LC-MS identified 1 921 differentially phosphorylated sites (20 tyrosine and 1 901 serine/threonine sites) across 851 proteins. Compared with controls, MI hearts exhibited significant phosphorylation upregulation at 1 545 sites and downregulation at 376 sites (P＜0.05). Conclusions This study delineates MI-associated phosphorylation dynamics, providing mechanistic insights and potential therapeutic targets for acute MI intervention.

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.

Lung transplantation is the ultimate therapeutic option for end-stage pulmonary diseases such as interstitial pneumonia, chronic obstructive pulmonary disease and pneumoconiosis. Currently, the shortage of allogeneic lung donors significantly limits the opportunity for end-stage lung disease patients to receive lung transplantation. In recent years, with the rapid development of biomedical engineering technologies, especially the major breakthroughs in genetic modification and cloning, xenogeneic lung transplantation has shown important potential for clinical translation. Among them, genetically modified pigs have become the most promising xenogeneic lung source due to the close similarity of organ size and physiological characteristics to humans, and the ability to perform targeted gene knockouts (such as α-Gal antigen knockout) to reduce the occurrence of hyperacute rejection. This article focuses on the research progress of porcine xenogeneic lung transplantation, systematically reviews the latest achievements and challenges in animal experiments and human trials, and introduces the technical experience accumulated by Shenzhen Third People's Hospital in the porcine-to-monkey xenogeneic lung transplantation model, in the hope of providing practical references for future research in this field.

Objective To explore the expert consensus on perinatal care management of infants with congenital heart disease(hereinafter referred to as"Consensus")in order to promote the standardization of integrated nursing.Methods The literature was systematically searched and several discussions were organized within the group to compile the first draft of the Consensus.From January to March 2024,20 experts in the clinical nursing,nursing management,clinical medicine and other fields of congenital heart disease were solicited through 2 rounds of Delphi,and 8 experts were invited to conduct a validation to revise the items to form the final Consensus.Results The recovery rates of the 2 rounds of questionnaires were 100％;the experts'authority coefficient was 0.89;the Kendall's W were 0.172,0.211,with statistical significance(P＜0.05).The Consensus included 8 first-level subjects,namely prenatal examination and consultation,postpartum screening,standardized referral,preoperative nursing,intraoperative nursing,postoperative nursing,other disease screening,health education and discharge follow-up.Conclusion The Consensus is scientific and rigorous,and it can provide a reference basis for clinical nursing staff to carry out the care and management of newborns with congenital heart disease.

Toxoplasma gondii is an obligate intracellular parasite that can invade the central nervous system(CNS)and cause complications such as encephalitis and schizophrenia.To migrate into the brain,T.gondii must cross restrictive cell barriers(blood-brain barrier,blood-cerebrospinal fluid barrier,and meninges).T.gondii migrates into the brain through transcellular or/and paracel-lular invasion and"Trojan horse"mechanisms,alone or in combination.The excessive inflammatory response after T.gondii infection destroys the blood-brain barrier and increases its permeability,thus further promoting the migration of T.gondii into the brain and causing persistent infection of the central nervous system.This review focuses on the mechanisms through which T.gondii migrates into the brain and the anti-T.gondii responses of brain parenchymal cells,to provide a deeper understanding of the pathogenic mecha-nisms of T.gondii and to offer insights for the development of novel therapeutic strategies.

This study investigates the expression pattern and functional significance of EF-hand domain-containing protein 2 (EFHD2) in hepatocellular carcinoma (HCC), with particular focus on its regulatory effects on tumor proliferation, migration, and invasion. Cellular experimental study was completed from June 2024 to January 2025 in the Basic Laboratory of the General Hospital of Southern Theater Command. TCGA database to determine EFHD2 expression and its clinicopathological correlations. GSCA database to assess methylation patterns and immune infiltration. Model of transient overexpression and knockdown of EFHD2 was constructed in hepatocellular carcinoma cells Hep3B, then RT-qPCR and Western blot were applied to verify the transfection efficiency. CCK-8 and colony formation assays for proliferation assessment, Transwell chambers for migration/invasion quantification. Protein-protein interaction networks were constructed via STRING, followed by GO/KEGG enrichment analysis. Statistical analysis was performed using the two independent samples t-test. The results showed that EFHD2 demonstrated significant upregulation in HCC tissues versus normal controls ( P<0.05). Elevated EFHD2 expression correlated with advanced clinical stage ( P<0.05) and poor differentiation ( P<0.05). In the CCK-8 assay, the EFHD2 overexpression group demonstrated significantly higher cell viability than the control group, as evidenced by 450 nm relative absorbance values on Day 1 (0.529±0.019 vs. 0.515±0.016, F=0.041, P=0.320), Day 2 (1.356±0.019 vs. 1.094±0.042, F=3.833, P<0.001), Day 3 (2.817±0.049 vs. 2.143±0.124, F=3.833, P<0.001), and Day 4 (3.848±0.015 vs. 3.430±0.021, F=0.469, P<0.001). The EFHD2 knockdown group showed reduced cell viability compared to controls: Day 1 (0.541±0.020 vs. 0.552±0.015, F=0.098, P=0.423), Day 2 (1.154±0.009 vs. 1.326±0.029, F=2.485, P<0.001), Day 3 (2.453±0.041 vs. 2.653±0.031, F=0.479, P<0.001), and Day 4 (3.685±0.038 vs. 3.836±0.021, F=6.804, P<0.001). In colony formation assays, the overexpression group displayed a significant increase in colony numbers (254.667±23.861 vs. 186.000±16.703, F=0.865, P=0.015), whereas the knockdown group exhibited decreased colony formation (229.000±24.637 vs. 306.667±36.501, F=0.988, P=0.038). In Transwell assays, the EFHD2 overexpression group revealed enhanced migratory capacity [ (605.000±72.670) cells vs. (472.667±28.095) cells, F=2.462, P=0.042] and invasive potential [(767.333±21.221) cells vs. (414.333±16.623) cells, F=0.331, P<0.001]. The knockdown group showed attenuated migration [(311.000±71.084) cells vs. (479.667±50.846) cells, F=0.718, P=0.029] and invasion [(247.667±48.263) cells vs. (345.667±32.130) cells, F=0.727, P=0.043] compared to controls. The network of EFHD2-interacting proteins was further constructed by the STRING database, and the GO and KEGG analysis were used to perform bioinformatics analysis reveal that EFHD2 is mainly involved in actin cytoskeleton regulation. In conclusion, EFHD2 is highly expressed in HCC and is involved in the process of proliferation, migration and invasion of HCC.

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.

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