Objective: To evaluate the safety and efficacy of therapeutic whole blood exchange combined with lymphoplasmapheresis in the treatment of refractory autoimmune hemolytic anemia (AIHA). Methods: A retrospective analysis was performed on the clinical data of AIHA patients who underwent therapeutic whole blood exchange combined with lymphoplasmapheresis at our hospital from March 2022 to May 2025. Efficacy was assessed by comparing changes in hemoglobin, platelet count, and bilirubin levels before and after treatment. Safety was evaluated by analyzing vital signs before and after the procedure, parameters during the exchange, and adverse reactions. Results: A total of 12 AIHA patients were enrolled, completing 19 exchange procedures. The number of procedures per patient ranged from 1 to 3. The median treatment duration was 67 (65-73) minutes, with a median exchange volume of 2 025 (1 851-2 121) mL, comprising 4.5 (4-6) units of red blood cells and 1 350 (1 200-1 400) mL of plasma. Ten patients achieved partial remission, one achieved complete remission, and one showed no response, yielding an response rate of 91% (11/12). After a single session, hemoglobin increased significantly by 17.58±9.85 g/L (P<0.01), while platelets counts decreased by 45 (17.5, 79)×10 /L (P<0.05), and both systolic and diastolic blood pressure showed a significant elevation (P<0.05). However, no statistically significant differences were observed in total bilirubin, indirect bilirubin, white blood cell count, or heart rate. During the procedures, 4 adverse reactions occurred in 3 patients: one child experienced severe heart rate fluctuation twice consecutively, and two adults developed plasma allergies. All reactions resolved spontaneously without pharmacological intervention. Conclusion: The combination of therapeutic whole blood exchange and lymphoplasmapheresis appears to be a safe and effective treatment for refractory AIHA patients.

Objective:To investigate the association of peripheral blood inflammatory markers and lymphocyte subsets with different severities of acute ischemic stroke(AIS).Methods:A total of 128 AIS patients who were admitted to Department of Neurology,The First Affiliated Hospital of Chongqing Medical University,from January to December 2022 were enrolled as subjects,and according to the National Institutes of Health Stroke Scale(NIHSS)score,the patients were divided into mild AIS group(67 patients with an NIHSS score of<4)and moderate-to-severe AIS group(61 patients with an NIHSS score of≥4).The two groups were compared in terms of baseline clinical data,blood biochemical parameters,and peripheral[MLR],neutrophil-to-lymphocyte ratio[NLR],and platelet-to-lymphocyte ratio[PLR]).Flow cytometry was used to measure the number and percentage of lymphocyte subsets.Results:Compared with the mild AIS group,the moderate-to-severe AIS group had a significantly higher proportion of patients with hyperlipidemia blood inflammatory markers(C-reactive protein[CRP],systemic immune-inflammation index[SII],monocyte-to-lymphocyte ratio(47.761%vs.67.213%,P=0.032),with relatively high values of low-density lipoprotein(LDL)/high-density lipoprotein(HDL)ratio(P=0.025)and total cholesterol(TCHO)/HDL ratio(P=0.020),as well as significantly higher levels of the peripheral blood inflamma-tory markers CRP(P<0.001),platelet count(P=0.001),MLR(P<0.001),and NLR(P<0.001),significantly higher numbers of periph-eral blood CD3 T cells(P=0.006),CD4 T cells(P=0.009),CD8 T cells(P=0.032),and CD3-/CD16+/CD56+NK cells(P=0.002),and a significantly higher proportion of T helper cells(P=0.041).The binary logistic regression analysis showed that platelet count(odds ratio[OR]=1.035,P=0.004),CRP(OR=2.016,P<0.001),NLR(OR=2.585,P=0.030),the proportion of total lymphocytes(OR=1.169,P<0.001),and the number of lymphocytes(OR=1.008,P<0.001)were significantly associated with moderate-to-severe AIS.The receiver operating characteristic(ROC)curve analysis showed that NLR,CRP,and the proportion of total lymphocytes had an area under the ROC curve of 0.760,0.812,and 0.777,respectively.Conclusion:Patients with moderate-to-severe AIS tend to have high levels of the peripheral blood inflammatory markers NLR and CRP,a high lymphocyte count,and a high proportion of lymphocytes.NLR,CRP,and the proportion of lymphocytes are independent risk factors for the development of moderate-to-severe AIS.

Kirsten rat sarcoma virus (KRAS) is a common oncogene in human cancers. Approximately 40% of the patients diagnosed with colorectal cancer (CRC) have KRAS mutations that exhibit strong resistance to targeted molecular therapy and EGFR antibody treatment. In this study, we present photocatalytic silica nanoparticles (A6-FS/BiVO₄ DMSNs) for targeted therapy of KRAS mutant CRC with the induction of cascadic ferroptosis events. Dendritic mesoporous silica nanoparticles (DMSNs) were impregnated with photocatalytic BiVO₄, loaded with ferroptotic agents (benzoyl ferrocene: B and sorafenib: S), and encoded with CD44-targeting A6 peptides. For the targeting design, we observed CD44 overexpression in KRAS mutant CRC cells using CPTAC data analysis. Upon laser irradiation, A6-FS/BiVO₄ DMSNs generate electron-hole pairs (e^-/h⁺), which produce hydroxyl radical (OH^·) and superoxide anions (O₂ ^{· -}). Laser irradiation simultaneously initiates the dissociation of iron (Fe²⁺) from benzoyl ferrocene and the release of sorafenib. This cascade induces ferroptosis in KRAS mutant CRC cells, especially under conditional inhibition of redox-regulating proteins (cystine/glutamate antiporter and glutathione peroxidase 4), and significantly inhibits tumor growth in a KRAS mutant CRC xenograft animal model.

Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.

Perimenopausal depression seriously affects women's physical and mental health.It is caused primarily by gonadal function decline,which is typically characterized by low mood,anxiety,slow thinking,and loss of interest,and is accompanied by autonomic dysfunction and endocrine dysfunction.The pathogenesis of perimenopausal depression remains unclear and controversial.Many scholars have conducted scientific research that is based on animal models of perimenopausal depression.Indeed,a good animal model of perimenopausal depression is the basic premise for studying its pathophysiological mechanisms and for facilitating reliability of the scientific result.Therefore,this paper combines the modern research mechanisms of perimenopausal depression and the current status of animal models in China,and provides an overview,evaluation,and generalization of the modeling method,principles and result,to provide a scientific basis and reference for the selection of suitable animal models for scientific research experiments.

Objective:To investigate the association between metabolic dysfunction-associated steatotic liver disease(MASLD)and the risk of adverse pregnancy outcomes,and to analyze the impact of the type and severity of cardiometabolic risk factor(CMRF)abnormalities on this association.Methods:A retrospective cohort study was conducted among primiparous women with singleton pregnancies who had registered at Beijing Friendship Hospital from March 10,2020,to December 31,2022.A total of 2 623 women were included.Basic characteristics and delivery outcomes were documented,liver ultrasound and relevant prenatal examinations were performed,and adverse pregnancy outcomes were diagnosed.Modi-fied Poisson regression models were used to analyze the association between MASLD and adverse pregnan-cy outcomes.The relationship between the type or severity of CMRF abnormalities in MASLD and the risk of adverse pregnancy outcomes was also explored.Results:After adjusting for confounding factors including age,gestational weight gain,and education level,MASLD was associated with an increased risk of cesarean section(RR=1.531,95％CI:1.304-1.799,P＜0.001),gestational diabetes melli-tus(GDM;RR=2.409,95％CI:1.948-2.979,P＜0.001),pregnancy-associated hypertension(PAH;RR=3.062,95％CI:2.069-4.533,P＜0.001),preterm birth(RR=2.145,95％CI:1.342-3.429,P=0.001),and large for gestational age(LGA;2.224,95％CI:1.599-3.095,P＜0.001).However,no significant associations were found for small for gestational age or postpartum hemorrhage.After adjusting for other CMRF abnormalities,the risk of adverse pregnancy outcomes varied among MASLD pregnant women with different CMRF abnormalities:the body mass index abnormal group had higher risks of cesarean section,GDM,PAH,preterm birth,and LGA;the glucose abnormal group had an increased risk of GDM;the blood pressure abnormal group had a higher risk of PAH;the high density lipoprotein cholesterol abnormal group had higher risks of cesarean section,GDM,and PAH;and the tri-glyceride abnormal group was associated with higher risks of GDM and preterm birth.Additional,as the severity of CMRF abnormalities increased,the risks of cesarean section(RR=1.199,95％CI:1.112-1.292,P＜0.001),GDM(RR=1.478,95％CI:1.345-1.624,P＜0.001),PAH(RR=1.626,95％CI:1.367-1.934,P＜0.001),preterm birth(RR=1.384,95％CI:1.120-1.710,P=0.003),and LGA(RR=1.422,95％CI:1.224-1.650,P＜0.001)continued to rise.Conclusion:MASLD during pregnancy is associated with an increased risk of multiple adverse pregnancy outcomes,and the type and severity of CMRF abnormalities significantly influence this association.These results suggest that attention should be paid to the specific CMRF abnormalities when diagnosed MASLD,as this may help to facilitate targeted interventions and reduce the risk of adverse pregnancy outcomes.

Objective:To describe the current status of responsive caregiving behavior of infant mothers,to analyze their influencing factors and pathways using the information-motivation-behavioral skills(IMB)model,and to provide a basis for further interventions related to responsive caregiving be-haviors and comprehensive promotion of early childhood development.Methods:This study was a cross-sectional survey using convenience sampling.Questionnaires were used to collect basic information about mothers and their infants,as well as data on mothers' responsive caregiving behavior,knowledge of re-sponsive caregiving,social support,and parenting self-efficacy.Multivariate linear regression models were employed to analyze the influencing factors of responsive caregiving behavior,and structural equa-tion modeling was used to analyze the pathways of these influencing factors.The criterion for inadequate responsive caregiving is defined as scores not exceeding the lower quartile(P25)of the total score.Results:Among 510 mothers of aged 0-12 months infants in Weifang City,the average score for respon-sive caregiving behavior was 16.41±3.99.The proportion of inadequate responsive caregiving was 25.7％.Mothers in the insufficient responsive caregiving group had lower scores in knowledge(7.70±1.41),social support(57.92±15.16),and parenting self-efficacy(30.36±6.48)compared with those in the sufficient group,with statistically significant differences(P＜0.001).Logistic regres-sion analysis indicated that the influencing factors for responsive caregiving included the level of know-ledge about responsive parenting[adjusted OR(aOR)=0.795,95％CI:0.566-0.838],social support(aOR=0.979,95％CI:0.961-0.996),and parenting self-efficacy(aOR=0.894,95％CI:0.857-0.932).Structural equation modeling revealed that knowledge of responsive caregiving(β=0.089,P=0.031),social support(β=0.153,P=0.001),and parenting self-efficacy(β=0.296,P＜0.001)were directly related to responsive caregiving behavior.Additionally,knowledge of responsive caregiving indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.095,P=0.014),and social support indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.497,P＜0.001).Conclusion:The current level of responsive caregiving behavior among mothers of 0-1-year-old infants in Weifang City is not satisfactory.Future development of responsive care-giving interventions should focus on providing caregivers with relevant knowledge of responsive caregiving based on their needs.Additionally,it is essential to offer social support from multiple aspects to enhance caregivers' parenting self-efficacy,thereby promoting improvements in responsive caregiving behavior.

Objective To explore the effect of hypoxia-inducible factor-1α(HIF-1α)inhibitor LW6 on ferroptosis in septic cardiomyopathy rats.Methods Rat septic cardiomyopathy model was prepared using cecal ligation and puncture(CLP)method.Thirty-six specific pathogen-free(SPF)6-8 weeks male SD rats were randomly divided into the sham-operated group,CLP group,CLP+solvent group,LW6 group,ferrostatin-1(Fer-1)group,and LW6+Fer-1 group.The degree of myocardial damage in each group was evaluated through hematoxylin-eosin stai-ning and detection of lactate dehydrogenase and creatine kinase content in cardiac tissue.Myocardial mitochondrial damage was observed by transmission electron microscopy.Ferroptosis level was determined by detecting iron ion concentration,reduced glutathione,malondialdehyde,and reactive oxygen species.Protein expression levels of HIF-1α,solute carrier family 7 member 11(SLC7A11),and glutathione peroxidase 4(GPX4)in cardiac tissue were detected by Western blotting.Results Compared with the CLP group and the CLP+solvent group,the LW6 group could ameliorate myocardial damage,alleviate mitochondrial damage,inhibit ferroptosis-related indicators(all P＜0.05),reduce HIF-1α protein expression levels(P＜0.05),and enhance SLC7A11 and GPX4 protein expression levels(both P＜0.05).Conclusion LW6 decreases HIF-1α expression and ferroptosis levels through the SLC7A11/GPX4 pathway,and ameliorates sepsis-induced cardiomyopathy.