ObjectiveTo observe the effect of M1 bone marrow-derived macrophages （M1-BMDM） with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis， and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDM^Wnt5a-KD cells. A rat model of liver cirrhosis induced by CCl₄/2-AAF was established， and at the end of week 8， rats were randomly divided into model group， M1-BMDM group， M1-BMDM Wnt5a-knockdown empty vector group （M1-BMDM^KD-EV group）， and M1-BMDM Wnt5a-knockdown group （M1-BMDM^Wnt5a-KD group）， with 6 rats in each group. On the first day of week 9， the rats in each group were given a single injection of the corresponding cells via the caudal vein， along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology， serum liver function parameters， hepatic stellate cell activation， and the expression levels of mature hepatocyte markers. 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 further comparison between two groups. ResultsCompared with the model group， all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase （AST） in serum （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group （P<0.05）. The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group， all cell treatment groups had a significant reduction in the percentage of CD68-positive area （all P<0.05）， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area （both P<0.05）. Compared with the model group， all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α （all P<0.05） and the protein expression level of CD68 （all P<0.01）； compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 （both P<0.05）， significant reductions in the protein and mRNA expression levels of CD68 （both P<0.05）， and a significant reduction in the protein expression level of tumor necrosis factor-α （P<0.01）. Sirius Red collagen staining and alpha-smooth muscle actin （α-SMA） immunohistochemical staining showed that compared with the model group， all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area， with the most significant changes in the M1-BMDM^Wnt5a-KD group， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue （all P<0.05）. Compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β （all P<0.05）. Compared with the model group， all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue （all P<0.05）， and the M1-BMDM^Wnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDM^KD-EV group （both P<0.05）. The M1-BMDM^Wnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDM^KD-EV group （P<0.01）. Immunofluorescence co-staining showed that compared with the model group， all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly higher number of such cells than the M1-BMDM^KD-EV group （P<0.05）. ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl₄/2-AAF， which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.

Nifedipine-induced gingival overgrowth (NIGO) refers to gingival hyperplasia caused by long-term use of the hypertensive drug nifedipine (NIF), and it is a drug adverse reaction. NIGO is characterized by a high incidence rate and a large patient base, and it is one of the most common types of gingival hyperplasia in clinical practice. Previous studies on the etiology of NIGO mainly focused on the pharmacological effects of NIF, while in recent years, it has been proposed that inflammation may also be a major risk factor for NIGO. Plaque is the initiating factor of periodontal inflammation. However, the role and mechanism of bacteria in the pathogenesis of NIGO remain unclear at present. Therefore, this article reviews relevant research and finds that bacteria may be involved in the pathogenesis of NIGO through the following pathways: ① Hypertensive drugs represented by NIF can cause dysbiosis of the oral flora, increasing the relative abundance of periodontal pathogenic bacteria. The inflammatory chemokines released by fibroblasts in the immune response to bacteria can work in synergy with NIF to promote excessive collagen production or recruit immune cells to participate in tissue fibrosis. ② Transforming growth factor-β (TGF-β) plays a significant role in fibrotic diseases. Bacterial infections can significantly increase the level of TGF-β, promoting epithelial-mesenchymal transition or allowing TGF-β and its downstream substances to directly participate in gingival fibrosis. ③ Bacteria can also cause massive proliferation of gingival fibroblasts, increased collagen synthesis and reduced degradation by activating the Wnt/β-catenin pathway, interfering with integrin α2β1 expression, and inhibiting miR-200 to alter the cell cycle, ultimately exacerbating NIGO. In conclusion, bacteria may be an important factor in aggravating NIGO, and oral health management for patients with hypertension should be given due attention. Future research can focus on the interaction between the oral microbiota and immune cells in NIGO patients, providing new strategies for their prevention and treatment.

Congenital blood group chimerism refers to the coexistence of two or more distinct blood types within an individual, resulting from the presence of hematopoietic cell populations with different genotypes. Consequently, red blood cells in such individuals may express different blood group antigens. Based on the timing and mechanism of formation, blood group chimerism can be classified as either congenital or acquired. Although congenital blood group chimerism is rare and involves complex mechanisms, it holds significant implications in transfusion medicine, transplantation, and obstetrics. This article reviews the formation mechanisms, detection methods, and clinical significance of congenital blood group chimerism in transfusion medicine. Particular emphasis is placed on the principles, advantages, and limitations of various detection techniques. Furthermore, the potential applications of these technologies in clinical diagnosis are discussed, providing a technical foundation for the development of precise transfusion strategies.

Background The Inner Mongolia Autonomous Region is a vast area with a wide array of ecological environments, resulting in considerable regional variations in air pollution characteristics. Current research is limited by a scarcity of systematic, region-wide studies and risk assessments. Objective To assess the health risks associated with inhalation exposure to nine heavy metal and metalloid elements in atmospheric fine particulate matter (PM_2.5) for the population of the Inner Mongolia Autonomous Region. Methods From the 10th to the 16th of each month throughout 2023, atmospheric PM_2.5 samples were collected at designated monitoring sites in 12 leagues (cities) across the Inner Mongolia Autonomous Region to analyze the characteristics and trends in concentration. The health risk assessment model developed by the United States Environmental Protection Agency was employed to evaluate both the non-carcinogenic and carcinogenic risks associated with the heavy metal elements beryllium (Be), cadmium (Cd), chromium (Cr), hydrargyrum (Hg), plumbum (Pb), manganese (Mn), and nickel (Ni) and the metalloid elements stibium (Sb) and arsenic (As). Results In 2023, a total of 1206 valid PM_2.5 samples were analyzed from the Inner Mongolia Autonomous Region. The annual average PM_2.5 concentrations in Inner Mongolia, as well as in the cities of Ordos, Wuhai, and the Alxa League, all exceeded the national limit of 35 μg·m⁻³. The PM_2.5 concentrations across the leagues (cities) exhibited a clear seasonal variation, peaking in winter, followed by spring, and reaching a minimum in summer and autumn. The median PM_2.5 concentration in Ordos throughout the year was higher than that in the other leagues (cities) of the region. Concerning health risks, the non-carcinogenic risks associated with the 9 elements detected in each league (city) were all below 1, indicating acceptable levels. However, the non-carcinogenic risk values for Mn, Cr, and As were relatively high; specifically, Ordos City displayed the highest non-carcinogenic risk values for Mn (7.74×10⁻¹) and Cr (2.97×10⁻²), while Chifeng City recorded the highest value for As (2.34×10⁻³). The carcinogenic risk values for As, Cd, Cr, and Ni fell within the range of 1×10⁻⁹ to 1×10⁻⁵, representing an acceptable level. The health risks varied with age, and the elderly residents faced the highest non-carcinogenic and carcinogenic health risks. Conclusion While the carcinogenic and non-carcinogenic risks from heavy metals and metalloids within atmospheric PM_2.5 in the Inner Mongolia Autonomous Region are generally within acceptable limits, the potential risks that Mn, As, and Cr pose to the health of elderly people warrants particular attention, and Ordos and Chifeng cities exhibit notably higher health risks among other areas. It is recommended that regular, long-term monitoring be conducted, taking into account the specific conditions at monitoring sites across each league (city), and that targeted air quality management strategies be implemented to protect public health.

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

OBJECTIVES: To investigate the mechanism through which salidroside inhibits proliferation of gastric cancer (GC) cells focusing on glucose metabolic reprogramming pathways. METHODS: High-throughput sequencing combined with bioinformatics analysis was employed to identify the potential targets of salidroside in human GC MGC-803 cells. Liposome-mediated transfection experiments were carried out to validate the functional and mechanistic roles of these targets. CCK-8 and colony formation assays were used to assess the effects of salidroside on GC cell viability and clonogenic ability. qRT-PCR, Western blotting, and biochemical assay kits were used to analyze the regulatory effects of salidroside on the miR-1343-3p-OGDHL/PDHB enzyme complex-pyruvate metabolic pathway in GC cells. RESULTS: Bioinformatics analysis suggested that the tumor-suppressive factor miR-1343-3p negatively regulated the key glycolytic enzyme gene oxoglutarate dehydrogenase-like (OGDHL) in GC cells, and OGDHL and pyruvate dehydrogenase E1 subunit beta (PDHB) were both significantly upregulated in GC tissues, which was close by correlated with reduced survival rates of GC patients. In MGC-803 cells, salidroside treatment significantly enhanced the expression level of miR-1343-3p and downregulated OGDHL expression, resulting in disruption of the stability of PDHB, reduced pyruvate oxidative decarboxylation, and consequently decreased production of acetyl-CoA and ATP. CONCLUSIONS Salidroside inhibits GC cell proliferation possibly by regulating the miR-1343-3p-OGDHL/PDHB enzyme complex-pyruvate metabolic pathway, which provides new insights into its anti-tumor mechanisms and suggests new strategies for targeted therapy for GC.
Humans ; Stomach Neoplasms/pathology* ; MicroRNAs/genetics* ; Cell Proliferation/drug effects* ; Glucosides/pharmacology* ; Phenols/pharmacology* ; Cell Line, Tumor ; Glucose/metabolism* ; Pyruvate Dehydrogenase (Lipoamide)/metabolism*

This article focuses on the application of artificial intelligence in clinical hematology laboratory teaching. By analyzing the current situation of clinical hematology test teaching and combining the advantages of artificial intelligence technology, this paper explores its application prospects in clinical hematology laboratory teaching from multiple perspectives, such as case library construction, atlas resource library construction, virtual simulation training, auxiliary teaching, and clinical thinking training, and analyzes the possible problems of artificial intelligence in teaching practice.

[Objective]Using data mining technology,to investigate the common syndrome types and acupoint compatibility rules of auricular point pressing beans in the treatment of pediatric enuresis,and provide reference for auricular point pressing beans in the treatment of pediatric enuresis.[Methods]A computer-based search of the literature on auricular point pressing beans for the treatment of pediatric enuresis from the establishment date of the database to January 8,2025.The search databases including Web of Science,PubMed,Cochrane library,CNKI,China Biology Medicine disc,VIP Database and Wanfang Medical Data.Descriptive analysis and association rule analysis were performed on the auricular data in the literature.[Results]A total of 90 articles were included,among which 88 were in Chinese and 2 in English.There were four main syndrome types in pediatric enuresis:syndrome of non-consolidation of kidney qi,syndrome of qi deficiencey of spleen and lung,syndrome of dampness-heat of liver channel,spleen-kidney deficiency pattern.There were 31 auricular points involved in the treatment of pediatric enuresis by auricular point pressing with beans,among which the commonly used auricular points were Bladder,Kidney,Subcortical Yuanzhong and Shenmen.The commonly used auricular acupoints for the treatment of pediatric enuresis were Bladder-Urethra-Yuanzhong-Subcortical-Kidney,Kidney-Shenmen-Yuanzhong-Bladder,and so on.[Conclusion]Data mining effectively identified common syndrome types of pediatric enuresis,frequently used auricular acupoints,and their combination patterns in auricular acupressure therapy.The findings revealed the characteristics and regularities of syndrome-based auricular nursing interventions,providing a scientific basis for acupoint selection in clinical practice and supporting the precise application of auricular acupressure in the nursing care of pediatric enuresis.

Objective To investigate the anatomical characteristics and clinical efficacy of femoral tunnel reconstruction in arthroscopic anterior cruciate ligament(ACL)reconstruction.Methods A total of 96 ACL tear patients treated at Guilin Hospital of Traditional Chinese Medicine Affiliated to Guangxi University of Chinese Medicine from September 2018 to October 2023 were selected as subjects.All underwent autologous peroneus longus tendon(PLT)grafting through a posteromedial approach,with femoral tunnel creation using an axial angle of 45° combined with a sagittal angle≥60°.Graft length,diameter,and tunnel dimensions were recorded in operative measurements.Coronal angle,tilt angle,and tunnel exit position measurements were measured before and after surgery.Anterior tibial distance,along with changes in International Knee Documentation Committee(IKDC),Lysholm,and Tegner scores were compared between preoperative and final follow-up.Results The average anterior tibial distance decreased from preoperative(5.8±2.3)mm to postoperative(3.3±1.6)mm.The mean IKDC score increased from(45.3±6.8)points to(85.7±5.2)points,the mean Lysholm score rose from(52.1±7.4)points to(89.6±4.9)points,and the Tegner score improved from(2.3±0.6)points to(6.5±1.1)points,with statistically significant(P＜0.001).Conclusion Axial angle 45° combined with sagittal angle ≥60° drilling constructs femoral tunnels ≥ 36mm in length,which align with PLT grafting characteristics,can effectively restore patient's knee stability and motor function.

This article explores the construction and practice of the"Party Building+Health Science Popularization"model,using the"Yixian Health Science Popularization Guangdong Tour"campaign conducted by Sun Yat-sen Memorial Hospital as a case study.The initiative has achieved remarkable results.Additionally,it summarizes innovative measures,as well as uni-versal and exemplary experiences,providing new insights and pathway recommendations for public hospitals to develop the"Party Building+Health Science Popularization"model.