Objective: To address systemic challenges in the blood system, such as supply-demand imbalance, inefficient allocation, and inappropriate clinical use, while bridging gaps in current theories regarding the integration of social mobilization, institutional practice, and policy coordination. It sought to construct a system dynamics model spanning from macro to micro levels to analyze the blood management system holistically. Methods: Key variables were identified by a systematic literature search in both Chinese and English databases. An improved Delphi method was then employed to conduct expert consultations across different fields, leading to the selection and determination of core variable sets for each sub-model. Furthermore, by defining their logical relationships, a system dynamics model was constructed to systematically analyze the operation mechanism of the blood management system. Results: Four core sub-models were developed: 1) A macro "Dynamic Balance" model quantifying regional supply-demand equilibrium and inventory control; 2) a mobilization "Three-Layer Funnel" model analyzing how socio-cultural factors, service channels, and policy incentives influence donation behavior; 3) an institutional "Dual-Cycle Regulation" model revealing hospital blood usage is driven by both disease burden (demand cycle) and management practices (regulation cycle); and 4) an individual "Three-Layer Filter" model standardizing clinical transfusion decisions based on necessity, risk-benefit, and context. These were integrated into a "Multi-Layer Linkage and Feedback" model, elucidating bidirectional interactions among five levels: policy environment, regional supply, blood station mobilization, hospital application, and clinical decision-making. Conclusion: This study constructed a system dynamics model for blood management. By defining key variables and their logical relationships, it systematically analyzes the system′s operational mechanism. The integrated framework connects multiple levels—regional supply, voluntary donation, hospital blood use, and clinical decision-making—revealing their intrinsic linkages. Future efforts should employ systems thinking to synergistically enhance supply-side mobilization, demand-side management, systemic regulation, and decision standardization to build a safe, efficient, and sustainable blood security system.

Oral submucous fibrosis (OSF), characterized by excessive deposition of extracellular matrix (ECM) that causes oral mucosal tissue sclerosis, and even cancer transformation, is a chronic, progressive fibrosis disease. However, despite some advancements in recent years, no targeted antifibrotic strategies for OSF have been approved; likely because the complicated mechanisms that initiate and drive fibrosis remain to be determined. In this review, we briefly introduce the epidemiology and etiology of OSF. Then, we highlight how cell-intrinsic changes in significant structural cells can drive fibrotic response by regulating biological behaviors, secretion function, and activation of ECM-producing myofibroblasts. In addition, we also discuss the role of innate and adaptive immune cells and how they contribute to the pathogenesis of OSF. Finally, we summarize strategies to interrupt key mechanisms that cause OSF, including modulation of the ECM, inhibition of inflammation, improvement of vascular disturbance. This review will provide potential routes for developing novel anti-OSF therapeutics.
Humans ; Oral Submucous Fibrosis/immunology* ; Extracellular Matrix/metabolism* ; Myofibroblasts

Objective To explore the relationship between CT quantitative left heart structure parameters and recurrence after hypertrophic cardiomyopathy(HCM)and atrial fibrillation(AF)radiofrequency ablation(RFCA).Methods A total of 120 patients with HCM and AF admitted to our hospital from April 2021 to June 2023 were selected.Patients were divided into the relapse group and the non-recurrence group according to whether RFCA recurred 6 months after operation.All patients underwent CT examination,and left ventricular ejection fraction(LVEF),left atrial ejection fraction(LAEF),left atrial volume index(LAVI)and left atrial auricular volume of the two groups were analyzed.The clinical data of patients were collected.Logistic regression model was used to analyze the influencing factors of postoperative recurrence of RFCA in HCM patients with AF.Receiver operating characteristic curve(ROC)curve was used to analyze the predictive efficacy of left heart structure parameters for postoperative recurrence of RFCA in HCM patients with AF.Results The volume levels of LAVI and left auricle were higher in the relapsed group than those in the non-relapsed group,and the level of LAEF was lower than those in the non-relapsed group(P＜0.05).Logistic regression analysis showed that persistent atrial fibrillation,LAVI and high left atrial appendage volume were independent risk factors for postoperative recurrence in HCM patients with AF(P＜0.05),and high LAEF was protective factor(P＜0.05).The results of ROC curve analysis showed that the AUC value of LAVI,LAEF and left atrial appendage volume in predicting recurrence after RFCA in patients with HCM and AF was 0.902,which was higher than that of 0.789,0.755 and 0.675 of each individual test.The combined prediction efficiency of the three tests was higher than that of each single test(Z=2.177,2.555 and 3.628,P＜0.05).Conclusion High level of LAVI and left atrial appendage volume and low level of LAEF are risk factors for postoperative recurrence of RFCA.The combined detection of the three methods has high predictive value for postoperative recurrence of RFCA in HCM patients with AF.

Objective To investigate the mechanisms by which astaxanthin(AST)alleviates oxaliplatin(OXA)-induced neuropathic pain through antioxidant pathways so as to provide theoretical basis for clinical intervention.Methods Animal experiments:SD rats were divided into five groups(n=6):control group,OXA(4 mg/kg)group,OXA+Oil group,OXA+AST(5 mg/kg)group,and OXA+AST(10 mg/kg)group.Mechanical and cold pain thresholds were measured at day 0,7,14,and 21.Malondialdehyde(MDA)content and superoxide dismutase(SOD)activity in the dorsal root ganglia(DRG)were detected using the thiobarbituric acid(TBA)method and WST-1 assay,respectively.Western blotting was performed to analyze the expressions of Nrf2 and HO-1.Cell experiments:neuro-2a cells were divided into control group,OXA(50 μmol/L)group,AST(10 μmol/L)group,and OXA(50 μmol/L)+AST(10 μmol/L)group.Cells were treated with nerve growth factor(NGF,50 ng/mL)to induce growth,and morphological changes were observed under an inverted microscope.Intracellular reactive oxygen species(ROS)level and mitochondrial superoxide were measured using DCFH-DA fluorescent probe and MitoSOXTM red,respectively.Mitochondrial function was assessed by JC-1 assay.Western blotting was used to detect Nrf2 and HO-1 expressions.Results Animal experiments:① Mechanical and cold pain thresholds were reduced in OXA and OXA+Oil groups(P＜0.05),while AST significantly increased these thresholds in OXA-treated rats(P＜0.05).② SOD activity decreased while MDA content increased in the DRG of OXA-treated rats(P＜0.05).AST restored SOD activity and reduced MDA level(P＜0.05,P＜0.01).③ Western blotting showed elevated Nrf2 and HO-1 expressions in OXA group(P＞0.05),which were further upregulated by AST(P＜0.05,P＜0.01).Cell experiments:① OXA reduced the number of neurite-bearing cells and shortened the average neurite length(P＜0.05).Inverted microscopic observation revealed that AST intervention increased both parameters(P＜0.01,P＜0.001).② OXA increased intracellular and mitochondrial ROS fluorescence intensity(P＜0.05),which was attenuated by AST(P＜0.01).③ JC-1 assay revealed decreased mitochondrial membrane potential in OXA group(P＜0.01),which was partially reversed by AST(P＜0.05).④ Western blotting results showed that OXA upregulated Nrf2 and HO-1 expressions(P＜0.05,P＜0.01),and AST further enhanced their levels(P＜0.01).Conclusion AST alleviates OXA-induced neuropathic pain by promoting Nrf2/HO-1 expression,enhancing SOD activity,reducing lipid peroxidation and ROS production,and improving mitochondrial function.

AIM:To explore the role of miR-195-5p in mediating trastuzumab resistance in gastric cancer and to validate its potential as a therapeutic target along with its target gene GPRC5A.METH-ODS:Trastuzumab-resistant gastric cancer cell lines(NCI-N87 and MKN45)were established.Cell viabili-ty under trastuzumab treatment was assessed us-ing CCK-8 assays.Expression levels of miR-195-5p were determined by RT-qPCR.Transfection with miR-195-5p mimics was performed to evaluate changes in trastuzumab sensitivity and prolifera-tion.GPRC5A expression was also measured by RT-qPCR,and the targeting relationship between miR-195-5p and GPRC5A was confirmed using a dual-lu-ciferase reporter assay.RESULTS:Parental cells showed higher sensitivity to trastuzumab than re-sistant cells,with miR-195-5p expression signifi-cantly lower in the latter.Overexpression of miR-195-5p in resistant cells enhanced trastuzumab sen-sitivity and reduced proliferation.GPRC5A was found to be upregulated in resistant cells,and miR-195-5p directly targeted GPRC5A,affecting cell pro-liferation under trastuzumab treatment.CONCLU-SION:miR-195-5p may regulate trastuzumab sensi-tivity in gastric cancer by targeting GPRC5A,sug-gesting potential as a molecular marker for trastu-zumab therapy guidance.

Objective:To analyze Hepatitis B virus(HBV)drug resistance mutations in patients with chronic hepatitis B(CHB)infection who have undergone long-term monotherapy with Entecavir(ETV)and those receiving combination therapy with ETV and Lamivudine(LAM), and to explore the related factors affecting HBV drug resistance mutations.Methods:The study retrospectively analyzed patients with CHB, compensated cirrhosis, decompensated cirrhosis, and liver cancer who received long-term nucleotide analogue antiviral therapy at the Fifth Medical Center of PLA General Hospital from August 2012 to August 2019.The patients were divided into an ETV monotherapy group and a combined LAM+ETV therapy group.Chi-square tests, independent sample t-tests, and Wilcoxon rank-sum tests were used to compare the clinical baseline characteristics and HBV drug resistance mutation features between the two therapy groups.A multivariate logistic regression model was used to analyze the factors related to HBV drug resistance mutations. Results:A total of 533 patients were enrolled in this study, 357 in the ETV monotherapy group and 176 in the LAM+ETV group. The ETV monotherapy group had 122 (34.17%) patients with resistance mutations, while the LAM+ETV group had 126 (71.59%).In general, the difference in gene mutation rate between the two therapy groups was statistically significant( χ2=66.337, P<0.001). The median age and alanine aminotransferase levels of patients with drug resistance mutations in the two therapy groups were higher than those in the non-mutation group[( t=-4.743, P<0.001)/( Z=-4.809, P<0.001), ( Z=-2.667, P=0.007)/( Z=-2.001, P=0.045)].Age( OR=1.044, 95% CI:1.023-1.066), compensated cirrhosis( OR=2.163, 95% CI:1.193-3.922), liver cancer( OR=4.017, 95% CI:2.170-7.436) and the treatment regimen( OR=6.075, 95% CI:3.889-9.489) were associated with drug resistance gene mutations( P<0.001).The mutation rates in different stages of chronic liver disease(CHB, cirrhosis, and liver cancer)showed statistically significant( χ2=41.038, P<0.001; χ2=15.894, P<0.001).The overall mutation rates of ETV-related genes in the two therapy groups were 25.49% and 32.39%, respectively.Additionally, 10 mutation sites and 38 variant combinations were identified, containing five common combinations being rtL180M, rtM204V, rtS202G;rtL180M, rtM204V, rtT184A; rtL180M, rtM204V, rtT184L;rtM204I and rtL180M, rtM204V. Conclusion:In CHB patients undergoing long-term therapy, the rate of HBV resistance mutations is higher in those receiving ETV and LAM combination therapy than in those receiving ETV monotherapy.Monitoring older patients and those with cirrhosis or liver cancer is especially important for preventing resistance mutations.

Objective:To investigate the CT image characteristics of anterior ethmoidal artery（AEA） through CT scan and its significance in nasal endoscopic surgery. Methods:A retrospective study of 82 patients（164 sides） with chronic sinusitis was conducted. All patients underwent CT scan and the images were reconstructed. The AEA classification was used and calculate the rate of AEA suspension. The AEA was classified, and the suspension rate of the AEA was calculated. The height of the lateral lamella of the cribriform plate （LLCP） was measured, and Keros classification was performed. The relationship between Keros classification and AEA suspension was analyzed. The supraorbital ethmoidal cell （SOEC） was identified, and its relationship with AEA suspension was analyzed. Results:Type Ⅰ AEA accounted for 42.07%（69/164）. Type Ⅱ AEA accounted for 22.56%（37/164）. Type Ⅲ AEA accounted for 35.37%（58/164）. The suspension rate was 35.37%. The average height of the LLCP was （3.7±1.8） mm. In the Keros classification, type Ⅰaccounted for 53.05%（87/164）, Type Ⅱaccounted for 37.80%（62/164）. Type Ⅲ accounted for 9.15%（15/164）. The results of the Spearman analysis showed that there was a moderate positive correlation between the Keros classification and the suspension of the AEA（r=0.526, P<0.01）. Among 164 sides, SOEC was present in 15 sides. The suspension rate of AEA in the group with SOEC was significantly higher than that in the group without SOEC（P<0.01）. Conclusion:Sinus CT and multiplanar reconstruction can clarify the image characteristics of AEA and its relationship with surrounding structures. When the level of Keros classification is higher or SOEC is present, the suspension rate of AEA increases significantly. It is of great significance to clarify the characteristics of AEA before surgery in order to avoid injury during surgery.
Humans ; Retrospective Studies ; Endoscopy ; Ethmoid Sinus/diagnostic imaging* ; Tomography, X-Ray Computed ; Arteries/diagnostic imaging* ; Sinusitis/diagnostic imaging* ; Male ; Female ; Middle Aged ; Adult ; Aged

Tumors exhibit abnormal glucose metabolism, consuming excessive glucose and excreting lactate, which constructs a tumor microenvironment that facilitates cancer progression and disrupts immunotherapeutic efficacy. Currently, tumor glucose metabolic dysregulation to reshape the immunosuppressive microenvironment and enhance immunotherapy efficacy is emerging as an innovative therapeutic strategy. However, glucose metabolism modulators lack specificity and still face significant challenges in overcoming tumor delivery barriers, microenvironmental complexity, and metabolic heterogeneity, resulting in poor clinical benefit. Nanomedicines, with their ability to selectively target tumors or immune cells, respond to the tumor microenvironment, co-deliver multiple drugs, and facilitate combinatorial therapies, hold significant promise for enhancing immunotherapy through tumor glucose metabolic reprogramming. This review explores the complex interactions between tumor glucose metabolism-specifically metabolite transport, glycolysis processes, and lactate-and the immune microenvironment. We summarize how nanomedicine-mediated reprogramming of tumor glucose metabolism can enhance immunotherapy efficacy and outline the prospects and challenges in this field.

OBJECTIVES: To investigate the mechanism of Qihuang Jianpi Zishen Granules (QJZ) for ameliorating renal damage in MRL/lpr mice. METHODS: With 6 female C57BL/6 mice as the normal control group, 30 female MRL/lpr mice were randomized into model group, QJZ treatment groups at low, moderate and high doses, and prednisone treatment group (n=6). After 8 weeks of treatment, the mice were examined for 24-h urine protein, creatinine and albumin levels, serum levels of IgG, complement 3 (C3), C4, anti-dsDNA, interferon γ (IFN‑γ) and interleukin 17 (IL-17). Kidney tissues were sampled for histopathological examination with HE staining and observation of glomerular ultrastructure changes using transmission electron microscopy (TEM). The expressions of MyD88/NF-κB pathway-related molecules in the kidney tissue were detected using RT-qPCR, Western blotting and immunohistochemistry. RESULTS: Compared with those in the model group, the mice treated with QJZ at the 3 doses and prednisone showed significant reductions in the renal injury biomarkers and serum IgG, anti-dsDNA, IFN‑γ and IL-17 levels and elevation of serum C3 and C4 levels. HE staining revealed lessened glomerular endothelial cell proliferation and mesangial thickening in all the treatment groups. TEM observation further demonstrated reduced electron-dense deposits and diminished inflammatory cell infiltration in the glomeruli in the intervention groups. QJZ at the 3 doses and prednisone treatment all significantly lowered renal expression levels of MyD88, NF-κB, p65 and p52 in the mouse models. CONCLUSIONS QJZ can improve renal damage in MRL/lpr mice possibly by inhibiting overactivation of the MyD88/NF-κB pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Mice, Inbred C57BL ; Mice, Inbred MRL lpr ; Myeloid Differentiation Factor 88/metabolism* ; Mice ; NF-kappa B/metabolism* ; Signal Transduction/drug effects* ; Kidney/metabolism* ; Interleukin-17

OBJECTIVES: To investigate the efficacy of Qihuang Jianpi Zishen Granules (QJZ) for inhibiting renal B cell differentiation in MRL/lpr mice and explore its underlying mechanism. METHODS: Thirty 8-week-old female MRL/lpr mice were randomly divided into model group, QJZ group, prednisone (Pred) group, QJZ+Pred group, and AIM2 inhibitor group (n=6), with 6 8-week-old female C57BL/6 mice as the normal control group. After treatments with normal saline, QJZ, Pred, or AIM2 inhibitor for 8 weeks, the mice were examined for urinary total protein-to-creatinine ratio (TPCR) and albumin-to-creatinine ratio (ACR), serum creatinine (Cr) and blood urea nitrogen (BUN) levels, and renal histopathology (with HE, Masson, and PAS staining) and ultrastructural changes (with electron microscopy). ELISA, immunohistochemistry, immunofluorescence staining and flow cytometry were used to detect blood levels of anti-dsDNA antibodies, cytokines and chemokines, renal deposition of complement components C3 and C4, renal expressions of AIM2, CD19, CD27 and CD138, and changes in splenic B lymphocyte subsets. The effect of QJZ on the AIM2/Blimp-1/Bcl-6 signaling axis was examined using Western blotting. RESULTS: QJZ treatment significantly improved Cr, BUN, TPCR and ACR in MRL/lpr mice, ameliorated renal pathologies, reduced the expressions of ds-DNA, BAFF, IL-21, CXCL12, CXCL13, C3 and C4, and increased IL-10 levels. QJZ significantly downregulated renal expressions of the key B-cell transcription factors Blimp-1 and XBP-1, upregulated Bcl-6 and PAX5 expressions, inhibited B-cell differentiation, and lowered the expressions of AIM2, CD27, CD138 and CD69. Inhibition of AIM2 similarly reduced renal Blimp-1 and XBP-1 expressions, increased Bcl-6 and PAX5 levels, suppressed B-cell differentiation, decreased IgG production, reduced C3 and C4 deposition, and alleviated renal pathology in MRL/lpr mice. CONCLUSIONS QJZ inhibits B cell differentiation and alleviates renal damage in systemic lupus erythematosus possibly by suppressing the AIM2/Blimp-1/Bcl-6 signaling pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred MRL lpr ; Female ; Mice ; Mice, Inbred C57BL ; Cell Differentiation/drug effects* ; B-Lymphocytes/drug effects* ; Proto-Oncogene Proteins c-bcl-6/metabolism* ; Kidney/drug effects* ; DNA-Binding Proteins/metabolism* ; Signal Transduction ; Lupus Nephritis