Red blood cells (RBCs), as a key component determining the hemorheological properties, play a significant role in the dynamic process of thrombosis by regulating blood viscosity, shear stress distribution, and complex molecular mechanisms (including promoting platelet activation, mediating interactions with vascular endothelial cells, and releasing procoagulant factors). This article systematically elucidates the multidimensional mechanisms of RBCs in hemostasis and thrombus formation by integrating perspectives from hemorheology and molecular biology. It focuses on analyzing how their physical properties and molecular activities dynamically interact and mutually regulate under hemodynamic conditions, collectively forming a complex thrombus formation network. This provides a comprehensive understanding of the pathophysiology of RBCs involvement in coagulation and offers references for developing bleeding and thrombotic risk assessment strategies, as well as precision diagnosis and treatment approaches that incorporate RBCs functions.

ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

Frontotemporal dementia (FTD) refers to a spectrum of neurodegenerative disorders primarily affecting the frontal and/or temporal lobes. Given the marked clinical, genetic, and pathological heterogeneity, achieving accurate antemortem diagnosis and pathological subtyping remains a significant challenge. Recent genetic studies have revealed differences in the genetic landscape of FTD across populations; meanwhile, progress in body fluid and peripheral tissue biomarkers, seed amplification assays, and neuroimaging technologies has provided powerful tools for pathology-based early diagnosis. The research focus in the field of FTD treatment has gradually shifted from symptomatic treatment to disease-modifying therapies and neuromodulation. This review focuses on the latest advances in clinical research of FTD, aiming to provide a reference for the formulation of precise diagnosis and treatment strategies for this disease.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

Occupational stress has been considered as one of the potential independent risk factors for the occurrence and development of hypertension in recent years. This paper reviews the concept connotation and common assessment methods of occupational stress, expounds the potential mechanisms by which occupational stress affects blood pressure levels, summarizes and analyzes the research progress of occupational stress-related hypertension in recent years, identifies existing issues in current research, and discusses future research directions, aiming to provide a reference for further understanding the relationship between occupational stress and hypertension and formulating effective intervention measures.

Objective:To compare the ecchymosis of affected limb in the prevention of deep vein thrombosis using low molecular weight heparin sodium and enoxaparin sodium after total knee arthroplasty.Methods:A total of 160 patients (31 males and 129 females) who underwent unilateral knee replacement in Department of Orthopedics of Chengdu Second People's Hospital from Oct. 2020 to Dec. 2023 were included. According to the random number method, all patients were evenly divided into the low molecular weight heparin sodium group (16 males and 64 females) and the enoxaparin sodium group (15 males and 65 females). All patients were treated with low molecular weight heparin sodium or enoxaparin sodium to prevent deep vein thrombosis in the lower limbs after surgery. The ecchymosis area on the affected limb was observed 7 days after surgery, and the incidence and difference in ecchymosis area between the two groups of patients were statistically analyzed. Simultaneously evaluate whether there are differences in hemoglobin, platelet, and coagulation related indicators between the two groups of patients before and after surgery.Results:There were no significant differences in hemoglobin, platelet, and coagulation parameters between the low molecular weight heparin sodium group and the enoxaparin sodium group before and after surgery ( t=1.13, -0.27, -0.47, 0.27, 0.34, -0.27, -0.89, -0.46, P=0.27, 0.34, 0.64, 0.83, 0.74, 0.97, 0.24, 0.65). The incidence of ecchymosis in patients with low molecular weight heparin sodium group and enoxaparin sodium group was 61.25% and 67.50%, respectively, with no statistically significant difference in the incidence of ecchymosis between the two groups ( P=0.41). The average size of ecchymosis in the two groups of patients was (40.40 ± 60.07) cm 2 and (37.41 ± 43.21) cm 2, respectively. And there was no statistically significant difference in ecchymosis area ( P=0.61) . Conclusion:Both patients had limbs’ecchymosis in the process of preventing deep venous thrombosis of lower limbs after total knee replacement. This indicates that the two anticoagulants had a certain effect on postoperative skin ecchymosis of total knee. And the incidence rate and area of ecchymosis of affected limbs were similar in the two groups.

Objective:To explore the relationship between life events, anxiety, depression, and behavior problems in adolescents.Methods:From September to October 2022, the cluster sampling method was used to select 5 341 adolescents from 4 middle schools in Xinxiang urban area.The subjects and their parents were investigated by the adolescent self-rating life events check list (ASLEC), generalized anxiety disorder scale (GAD-7), patient health questionnaire (PHQ-9), and child behavior checklist (CBCL). SPSS 27.0 software was used for Spearman correlation analysis, and AMOS 28.0 software was used to construct the structural equation model.Results:The scores of anxiety, depression, and behavioral problems were 1 (0, 4), 1 (0, 4), and 3 (0, 10). The total score of life events was 5 (1, 13), and the dimensions scored as follows: interpersonal conflict 1 (0, 4), academic pressure 2 (0, 5), punishment 0 (0, 2), loss 0 (0, 0), health and adaptation problem 0 (0, 1), and others 0 (0, 2). There were positive correlations between life events and its dimensions, depression, anxiety and behavioral problems ( r=0.28-0.69, all P<0.01). In the overall population, anxiety and depression played parallel mediating roles in the impact of life events on behavior problems. Life events could positively predict anxiety ( β=0.68, P<0.01), and anxiety could positively predict behavior problems ( β=0.04, P=0.02). Life events could positively predict depression ( β=0.77, P<0.01), and depression could positively predict behavior problems ( β=0.18, P<0.01). The standardized total effect size of the impact of life events on behavioral problems was 0.622 (95% CI=0.564-0.675). The standardized direct effect size and indirect effect size were 0.460 (95% CI=0.374-0.539) and 0.162 (95% CI=0.108-0.218), accounting for 74.0% and 26.0%of the total effect, respectively. After stratification by gender, the results for male adolescents were consistent with the overall population, while the mediating effect of anxiety was not significant in the female adolescents. Conclusion:Life events can lead to anxiety and depression in adolescents, thereby increasing the risk of behavior problems.

Objective To analyze the clinical characteristics and prognostic risk factors of patients with atrial fibrillation(AF)related to septic shock admitted to the intensive care unit(ICU).Methods This retrospective cohort study included 152 patients with septic shock who were admitted to the ICU between January 2020 and December 2023.Patients were categorized into AF(n=48)and non-AF(n=104)groups based on the occurrence of AF.Clinical parameters were compared between the two groups,and variables with statistically significant differences(P<0.05)were entered into a multivariate logistic regression analysis to identify clinical features associated with AF.Patients were also stratified into survival(n=103)and death(n=49)groups based on 28-day outcomes.Variables showing signifi-cant intergroup differences(P<0.05)were further included in a multivariate model to identify independent risk factors for mortality.Kaplan-Meier survival analysis was performed using AF as a binary variable,and log-rank tests were applied to compare survival curves.Results The incidence of AF was 31.58%among patients with septic shock.Compared with the non-AF group,the AF group was older,received higher cumulative doses of vasoactive agents,and had elevated levels of lactate(Lac),N-terminal brain natriuretic peptide precursor(NT-proBNP),troponin I(cTnI),tumor necrosis factorα(TNF-α),and C-reactive protein(CRP).The AF group also had higher E/e'ratios,left ventricular ejection fraction(LVEF),Acute Physiology and Chronic Health Evaluation-Ⅱ(APACHEⅡ)scores,Sequen-tial Organ Failure Assessment(SOFA)scores,and 28-day mortality rates(all P<0.05).Multivariate logistic regression identified age(odds ratio[OR]=1.060,P=0.015),SOFA score(OR=1.525,P=0.001),TNF-α(OR=1.009,P=0.026),CRP(OR=1.008,P=0.002),and E/e'(OR=1.363,P=0.023)as independent risk factors for AF.The 28-day mortality rate was 32.24%.Compared with survivors,non-survivors had significantly higher Lac,cTnI,E/e',LVEF,and TNF-α levels,higher APACHEⅡand SOFA scores,longer ICU stays,and a higher incidence of AF(all P<0.05).Multivariate analysis identified SOFA score,cTnI,E/e',and AF as independent predictors of 28-day mortality.Kaplan-Meier analysis revealed significantly poorer survival in patients with AF(χ2=6.747,P=0.009).Conclusion AF is common in ICU patients with septic shock.Advanced age,greater organ dysfunction,elevated inflammatory markers,and diastolic dysfunction are associated with AF occurrence.Organ dysfunction,myocardial injury,diastolic dysfunction,and AF are inde-pendent predictors of mortality in this population.Greater clinical attention is warranted in patients with AF and septic shock due to their elevated risk of poor outcomes.