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.

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.

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.

Objective : To analyze the relationship between tongue volume, tongue position, dental and skeletal parameters in adult patients with different skeletal malocclusions, providing references for the etiology, diagnosis, and treatment of skeletal malocclusions. Methods: This study has been reviewed and approved by the Ethics Committee, and informed consent has been obtained from patients. Cone-beam computed tomography (CBCT) and cephalometric radiographs were collected from 60 adult patients, divided into three groups based on ANB angle values: skeletal Class I (0° < ANB < 4°), II (ANB > 4°), and III (ANB < 0°), with 20 cases in each group. Dental and skeletal parameters were measured using Dolphin software. Mimics software was used for 3D reconstruction of the tongue, oral cavity, and upper airway to measure tongue position, tongue volume, oral cavity volume, and upper airway volume, followed by statistical analysis. Results: The skeletal Class III group had significantly larger tongue and oral cavity volumes than the skeletal Class I and Class II groups (P = 0.02). Tongue length in the skeletal Class III group was also greater than in the skeletal Class I and Class II groups (P = 0.016). There was no significant difference in the ratio of tongue volume/oral cavity capacity among the three skeletal malocclusion groups (P > 0.05). Tongue volume was positively correlated with U1-SN and negatively correlated with overbite and overjet (P < 0.05). Additionally, tongue volume showed a significant positive correlation with Go-Gn and Pg-Np (P < 0.01), as well as with maxillary and mandibular dental arch width and basal bone arch width (P < 0.01). Upper airway volume was positively correlated with TT-VRL and TP-VRL (P < 0.05). Conclusion Patients with skeletal Class III malocclusion have larger tongue volumes and longer tongues. Patients with larger tongue volumes may also have larger, more forward-positioned mandibles. Patients with more posterior tongue positions may have smaller upper airway volumes. When developing orthodontic or orthognathic treatment plans, it is crucial to consider the relationship between tongue position, tongue volume, the jaws, and the airway to ensure optimal outcomes for both dental and orofacial function.

Objective:To compare the differences in clinical characteristics among the patients at clinical high risk for bipolar disorder(CHR-BD),the patients with bipolar disorder(BD),and the healthy controls(HC)at low risk,and to provide the basis for the diognasis and treatment of CHR-BD.Methods:For the first time,the BD risk criteria and prospective structured assessment tools were jointly used in outpatients aged 16-30 years,and 43 CHR-BD patients were included to ensure the accuracy of the assessment.Meanwhile,33 BD patients and 32 HC subjects were also enrolled.The clinical symptoms,neurocognitive function,and global functional levels of the subjects in the three groups were evaluated using observer-rated and self-rated tools.The CHR-BD and BD groups were combined,and Logistic regression analysis was used to identify the independent influencing factors related to diagnostic status;Pearson or Spearman correlation analysis was used to analyze the correlations between the global functional levels and the symptoms or neurocognitive characteristics of the patients in CHR-BD and BD groups.Results:There were statistically significant differences in the scores of symptom and global functional level scales among HC,CHR-BD,and BD groups(P<0.05).Compared with HC group,the scores of mood symptoms(anxiety,depression,and mania/hypomania),psychotic symptoms,total affective temperament questionnaire scores,and some dimensions(cyclothymic,depressive,irritable,and anxious temperaments)in CHR-BD and BD groups were significantly increased(P<0.001),while the global functional levels were significantly decreased(P<0.001).Compared with BD group,the lowest global functional level score in the past year in CHR-BD group was significantly increased(P=0.022),while the current global functional level score was significantly decreased(P=0.005).No significant differences were observed in neurocognitive function scores among the three groups(P>0.05).The lowest global functional level score in the past year was an independent influencing factor for BD diagnosis[odds ratio(OR)=0.952,95%confidence interval(CI):0.917-0.988,P=0.010].In both CHR-BD and BD patients,the current global functional levels were negatively correlated with depressive(r=-0.417,P=0.005;r=-0.617,P<0.001)and anxiety symptoms(r=-0.360,P=0.018;r=-0.506,P=0.003).In BD patients,the current global functional level was negatively correlated with lifetime manic/hypomanic symptoms(r=-0.360,P=0.039),psychotic symptoms(r=-0.502,P=0.003),and affective temperament scores(r=-0.479,P=0.005),while the lowest global functional level in the past year was negatively correlated with lifetime manic/hypomanic symptoms(r=-0.391,P=0.024).Conclusion:CHR-BD patients share similar mood symptom characteristics with BD patients,and their global functional levels are negatively correlated with depressive and anxiety symptoms.BD patients exhibit worse lowest global functional levels in the past year,and their global functional levels are negatively correlated with manic/hypomanic symptoms.

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*

BACKGROUND:Research on adipose-derived mesenchymal stem cells and their exosomes often uses proteomics to analyze their roles in tissue repair,but comparative proteomic analyses between the two are scarce.OBJECTIVE:To analyze adipose-derived mesenchymal stem cells and their exosomes using proteomic analysis.METHODS:Rat adipose-derived mesenchymal stem cells were isolated,cultured,and identified.Exosomes were then extracted from cell supernatant and identified.Differentially expressed proteins of adipose-derived mesenchymal stem cells and their exosomes were analyzed using DIA proteomics.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed on these differentially expressed proteins.RESULTS AND CONCLUSION:(1) Adipose-derived mesenchymal stem cells displayed a mainly spindle-shaped,fibroblast-like morphology.(2) The exosome suspension protein concentration was 7.66 mg/mL,as determined by the BCA method.(3) Exosomes exhibited a characteristic teacup shape with a visible double-layer membrane vesicle structure.The center presented a low electron density component.The exosomes showed a peak particle size distribution of 112.2 nm,a concentration of 7.5×1011 particles/mL,and an average diameter ranging from 70 to 140 nm.(4) Exosomes expressed high levels of surface marker proteins CD9 and TSG101.(5) Gene Ontology analysis of differentially expressed proteins revealed enrichment in the extracellular matrix and synapses,with functions related to ion binding,ribosome binding,and particularly cell adhesion and translation.(6) Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the differentially expressed proteins were primarily involved in extracellular matrix receptor interaction,ribosome,and cytokine receptor interaction,and also associated with various metabolic diseases like cholesterol and thyroid disorders.

Objective:To adapt and validate the Chinese version of the Supervisory Relationship Questionnaire(SRQ)and evaluate its psychometric properties among supervisees.Methods:Item analysis,exploratory factor anal-ysis(EFA)and confirmatory factor analysis(CFA)were conducted on data from 888 supervisees recruited via on-line platform.Test-retest reliability over a four-week interval was examined in a randomly selected subset of 70 su-pervisees.An additional sample of 367 supervisees completed the Supervisory Relationship Scale(SRS)to evaluate criterion validity.Results:The revised SRQ contained 65 items and 6 factors.Both exploratory factor analysis and confirmatory factor analysis supported six-factor structure(safe base,structure,commitment,reflective education,role model and formative feedback),explaining 66.52％of the variance,with factor loadings of the items ranging from 0.58 to 0.83.The revised SRQ had six factors with good fit indices(x2/df=1.31,GFI=0.81,NFI=0.87,CFI=0.97,TLI=0.90,IFI=0.91,RMSEA=0.03,SRMR=0.05).The scores of the revised SRQ were positively correlated with the scores of SRS(ICC=0.96,P＜0.01).The Cronbach α coefficient of the revised SRQ was 0.97,and the test-retest reliability coefficient(ICC)was 0.74.Conclusion:The SRQ-C demonstrates sound psy-chometric properties,including structural validity,criterion-related validity,internal consistency,and temporal stabil-ity.It is a reliable and valid instrument for assessing supervisory relationships from the supervisee perspective.

OBJECTIVE To investigate the in vitro antitumor activity and in vivo targeting of nanopolymers co-loaded with arse-nic trioxide(ATO),an active ingredient of traditional Chinese medicine arsenic,and photosensitizer(IR780)to activate the patient's own immune system in the treatment of brain glioma in synergistically with chemotherapy and phototherapy.METHODS PLGA/AI containing ATO and IR780 was prepared by volatilization with multiple emulsion solvent.The particle size,potential and polydispersity index(PDI)were determined by dynamic light scatterometer(DLS)at different feed ratios.Transmission electron microscopy(TEM)was used to detect the morphology of PLGA/AI.Fluorescence spectrophotometer was used to investigate the spectroscopic characteris-tics.UV-vis spectrophotometer was used to determine the drug loading and encapsulation rate of IR780.Under laser irradiation,the physiological release of ATO was measured by dialysis bag method.The uptake of PLGA/AI in GL261 cells was photographed by confo-cal microscopy(CLSM).The cell uptake mechanism of PLGA/AI was investigated by flow cytometry(FCM).3D tumor spheroid mod-el was constructed to simulate the deep penetration of PLGA/AI in solid tumors.The synergistic anti-tumor effects of PLGA/AI in vitro were studied by MTT assay and dying staining.DCFH-DA staining and FCM determination of the co-expression of CD80 CD86 co-stimulatory molecules verified the immune activation induced by PLGA/AI in vitro photochemotherapy.The in vivo targeting of PLGA/AI and the tissue distribution of the main organs were investigated by means of in vivo imaging of small animals after tail vein injection.RESULTS The optimal ratio of ATO to IR780 was 1∶10,its particle size was(134.11±2.19)nm,Zeta potential was(-7.02±0.649)mV,PDI was 0.254±0.059,and it was a uniform spherical shape under TEM.The fluorescence spectra showed that IR780 was successfully loaded onto PLGA,and the drug loading and encapsulation rate of IR780 in PLGA/AI were(2.53±0.02)%and(71.26±0.38)%respectively.The results of in vitro release experiments showed that ATO could be released in response to laser light by IR780-mediated photo-dynamics.Cell uptake experiments showed that the nano-polymer could effectively enter tumor cells under clathrin-mediated endocytosis.In vitro investigation of cell viability,ROS detection and dendritic cell maturation experiment showed that it could effectively kill tumor cells by inducing a large amount of ROS to generate and activate immune cells.In vivo targe-ting and biological distribution study confirmed that PLGA/AI could effectively penetrate BBB into tumor sites.CONCLUSION The active ingredients of traditional Chinese medicine arsenic,ATO and IR780,use PLGA as carriers to form nano-polymers through the volatilization of multiple emulsion solvents,which can cross the BBB and effectively accumulate at the tumor site.Based on"strengthe-ning the healthy qi and eliminating pathogenic factors"and combined with chemotherapy and photo-immune activation,it has the po-tential for long-term anti-glioblastoma treatment.