Objective: To report the antibody identification, blood management during pregnancy and the monitoring process of fetal hemolytic disease of fetus and newborn (HDFN) in a pregnant woman with a history of blood transfusion and pregnancy who developed anti-Jr . Methods: Saline tube technique and anti-human globulin technique were used for maternal blood typing, unexpected antibody screening and identification, as well as for determining antibody titer and IgG subclasses. PCR-SSP was employed for genotyping of 18 blood group systems. Next-generation sequencing (NGS) was utilized for gene sequencing of 38 blood group systems. Sanger sequencing was applied to verify rare blood group mutations detected by NGS and to investigate the corresponding rare blood group genes in family members. Blood preparation was achieved through anemia management in prenatal clinics and autologous blood collection during pregnancy. The newborn underwent the three primary tests for HDFN and plasma IgG subclass testing. Results: The pregnant woman's blood type was B, RhD positive, with a positive unexpected antibody screen, and the antibody identification pattern was consistent with a high-frequency antigen antibody. Gene sequencing revealed a homozygous ABCG2 c.376C>T mutation in the woman, resulting in the Jr(a-) phenotype, and anti-Jr antibody was present in her plasma. No compatible Jr(a-) blood was found among family members. The maternal anti-Jr IgG titer remained stable at 256 during pregnancy, with no detectable IgG1 or IgG3 subclasses against the Jr antigen. A total of 800 mL of autologous blood was collected in two stages during pregnancy. The newborn was B, RhD positive, Jr(a+), with a positive unexpected antibody screen (anti-Jr ). IgG subclass typing detected no IgG1 or IgG3. The direct antiglobulin test was positive, while the acid elution test was negative. Conclusion: The combination of serology and blood group genetic analysis provides a diagnostic basis for identifying antibodies to high-frequency antigens. Managing perinatal anemia and implementing staged autologous blood storage can secure blood supply for the perioperative period. IgG antibody subclass typing offers a reference for clinical assessment and prevention of HDFN.

ObjectiveTo investigate the potential mechanism of Yiqi Yangyin Huoxue Formula （益气养阴活血方， YYHF） in the treatment of membranous nephropathy （MN） based on the NOX4-mediated stromal cell-derived factor-1α（SDF-1α）/CXC chemokine receptor 4 （CXCR4） signaling pathway. MethodsA total of 42 male SD rats were randomly divided into blank group （n=6） and modeling group （n=36）. The modeling rats were given a single injection of sheep antirat Fx1A （6 ml/kg） serum into the tail vein to establish MN model. Thirty-six rats with successful modeling were further divided into model group （normal saline， 10 ml/kg）， benazepril group （10 mg·kg^-1·d^-1）， the medium-dose YYHF group （11.0 g·kg^-1·d^-1） and high-dose YYHF group （22.0 g·kg^-1·d^-1）， with 9 rats in each group. All groups received daily intragastric administration for 6 consecutive weeks. During the experimental period， the general condition of rats in each group was observed. After gavage administration finished， a fully automated biochemical analyzer was used to measure the 24-hour urine total protein （24 h-UTP） and serum biochemical parameters， including albumin （ALB）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， serum creatinine （SCr）， total cholesterol （TC）， and triglyceride （TG）. Hematoxylin-eosin （HE） staining and periodic acid-silver metheramine （PASM） staining were used to observe the histopathological changes of renal tissues in each group of rats. The levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were detected by ELISA. The protein expression levels of NOX4， SDF-1α， CXCR4， Nrf2， nuclear factor kappa B subunit p65 （NF-κB p65） and podocyte slit diaphragm protein nephrin in rat renal tissues were detected by Western Blotting. The mRNA expressions of NOX4， SDF-1α， CXCR4， Nrf2， NF-κB p65 and Nephrin in renal tissues were detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultsCompared to the blank group， rats in the model group exhibited typical features of MN， including lethargy， reduced activity， dull and coarse fur， marked edema， and massive proteinuria. Compared to the model group， these abnormal conditions were improved to varying degrees in all treatment groups. The high-dose YYHF group showed a level of improvement comparable to that of the benazepril group， with overall recovery superior to that of the medium-dose YYHF group. Compared to the blank group， the model group showed increased levels of 24 h-UTP， BUN， SCr， TC and TG， decreased level of ALB， increased levels of MDA and protein and mRNA expressions of NOX4， SDF-1α， CXCR4 and NF-κB p65 in renal tissue， along with decreased levels of SOD and protein and mRNA expressions of Nrf2， Nephrin （P＜0.01）， accompanied by severe renal pathological damage. Compared to the model group， the benazepril and the medium- and high-dose YYHF groups showed significant improvements in the above indicators （P＜0.01）， along with alleviation of renal pathological injury. The 24 h-UTP level in the high-dose YYHF group was lower than that in the medium-dose group （P＜0.01）， while no statistically significant difference was observed among the other treatment groups （P＞0.01）. ConclusionYYHF may alleviate oxidative stress and inflammatory responses by down-regulating the expression of NOX4 and inhibiting the SDF-1α/CXCR4-Nrf2 signaling pathway， thereby improving podocyte damage and protecting renal function.

Exercise-induced muscle damage (EIMD) is a frequent form of skeletal muscle microdamage that occurs after high-intensity, prolonged, or unaccustomed exercise, especially exercise dominated by eccentric contractions. It is commonly characterized by delayed-onset muscle soreness, transient loss of muscle strength, local inflammation, structural disruption of myofibers, and delayed functional recovery. Although mild EIMD may serve as a stimulus for training adaptation, excessive or insufficiently recovered muscle damage can impair exercise performance, disturb training continuity, and reduce participation in physical activity. Therefore, clarifying the molecular mechanisms that underlie the initiation, amplification, and resolution of EIMD is important for optimizing athletic training, improving post-exercise recovery, and guiding evidence-based public fitness practice. Necroptosis is a regulated form of programmed cell death mediated primarily by the receptor-interacting protein kinase (RIPK) 1/RIPK3/mixed lineage kinase domain-like protein (MLKL) signaling axis. Recent studies have shown that necroptosis is closely involved in tissue injury, sterile inflammation, and repair remodeling. However, whether necroptosis acts as an initiating driver, a secondary damage amplifier, or an adaptive signal required for repair after EIMD remains unclear. This review aimed to summarize the potential role of necroptosis in EIMD and to establish a mechanistic framework linking regulated cell death, inflammatory amplification, immune regulation, and skeletal muscle repair. Relevant studies concerning EIMD, necroptosis, RIPK1/RIPK3/MLKL signaling, damage-associated molecular patterns (DAMPs), inflammatory responses, immune cell recruitment, extracellular matrix remodeling, and muscle regeneration were reviewed and integrated. On this basis, the possible temporal and functional involvement of necroptosis in different phases of EIMD was analyzed. The main evidence summarized in this review suggests that EIMD is not merely a consequence of primary mechanical disruption. Instead, it develops through a dynamic sequence that includes sarcolemmal instability, calcium overload, mitochondrial dysfunction, oxidative stress, inflammatory mediator production, immune cell infiltration, necrotic tissue clearance, and regeneration-associated remodeling. Necroptosis may participate in this process through at least two interconnected mechanisms. First, in the early or progressive phase of EIMD, activation of the RIPK1/RIPK3/MLKL signaling axis may promote MLKL phosphorylation and plasma membrane permeabilization, leading to the release of DAMPs such as high-mobility group box 1, ATP, mitochondrial DNA, and other intracellular components. These signals may activate innate immune pathways, amplify inflammatory cytokine production, and enhance the recruitment of neutrophils and macrophages, thereby aggravating secondary inflammation and extending muscle fiber injury. Second, during the resolution and repair phases, necroptosis-related signaling may also contribute indirectly to the formation of a regenerative microenvironment. By influencing the clearance of necrotic debris, the recruitment and phenotypic transition of immune cells, and the remodeling of extracellular matrix components, necroptosis may affect satellite cell activation, myogenic repair, and the eventual structural and functional recovery of injured skeletal muscle. Thus, the biological effect of necroptosis in EIMD may be context dependent rather than uniformly harmful. Its outcome may depend on exercise intensity, the extent of tissue damage, the timing of pathway activation, the involved cell types, inflammatory status, training background, age, and metabolic condition. In conclusion, necroptosis may represent an important molecular link between skeletal muscle injury, sterile inflammation, and tissue repair after damaging exercise. It may exert a dual role in EIMD by amplifying secondary damage while also contributing to repair coordination under appropriate temporal and microenvironmental conditions. Future studies should determine the activation pattern of RIPK1/RIPK3/MLKL signaling after different exercise protocols, identify the major cell populations undergoing necroptosis in injured skeletal muscle, and examine whether targeted modulation of necroptosis can reduce excessive inflammation without impairing necessary regenerative responses. This review provides a theoretical basis for understanding the pathogenesis of EIMD and for developing targeted strategies to improve skeletal muscle recovery after exercise-induced injury.

Endometrial injury disease is a kind of uterine disease of thin endometrium and intrauterine adhesion caused by endometrial basal layer damage.The current clinical use of drug therapy and hysteroscopy surgery can not have good curative effects.Mesenchymal stem cells(MSCs)and platelet-rich plasma(PRP)can secrete a variety of active factors to regulate the inflammatory response and immune response of endometrial,promote endometrial proliferation and repair,and there is a mutual promoting effect between the two.Combined use can provide a new idea for the clinical treatment of endometrial injury diseases.

Objective To investigate the effects of light-at-night exposure on anxiety and depression behaviors in mice and to explore the underlying neural mechanisms.Methods Six-week-old male C57BL/6J mice were randomly assigned to a control(Ctrl)group and a light-at-night exposure(LAN)group.Mice in the LAN group were exposed to 460 nm blue light for 1 h daily during the zeitgeber time(ZT)13-14 while the Ctrl group mice were maintained under a 12-h light/12-h dark cycle.Behavioral tests were conducted at different time points following LAN exposure to evaluate anxiety and depression behaviors in the mice.Immunofluorescence staining was used to observe the effect of LAN on c-fos expressions in the medial prefrontal cortex(mPFC),basal ateral amygdala(BLA),paraventricular nucleus(PVN)and paraventricular thalamus(PVT).ELISA was performed to measure changes in serum corticosterone,adrenocorticotropic hormone(ACTH)and corticotropin-releasing hormone(CRH)levels.Golgi staining was applied to measurethe dendritic spine density and morphology from mPFC and CA1.Western blotting analysis was conducted to detect expression levels of brain-derived neurotrophic factors(BDNFs),phosphorylated tropomyosin receptor kinase B(p-TrkB)/TrkB,postsynaptic density protein 95(PSD95)and synaptophysin(SYP)in the mPFC.Results Mice exhibited anxiety-like behaviors after 14 days of LAN exposure,with depression-like behaviors emerging after 28 days.LAN exposure of 28 days led to a significant increase in the number of c-fos-positive neurons in the mPFC,BLA,PVN and PVT(P＜0.05),resulted in elevated serum corticosterone levels(P＜0.01)and reduced protein expression levels of BDNF and SYP(P＜0.05).Furthermore,there was a marked decrease in synapse numbers and synaptic density in the mPFC(P＜0.01).Conclusion Prolonged exposure to blue light at night enhances neuronal activity in the mPFC and BLA and suppresses the BDNF/TrkB signaling pathway by activating the hypothalamic-pituitary-adrenal axis(HPA),thus leading to synaptic structural and functional damage and inducing anxiety and depression behaviors in mice.

Objective:To explore the characteristics of social skills and problem behaviors of children and adolescents with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), as well as the association with core symptoms.Methods:A total of 409 patients aged 5-18 years old with ASD or ADHD in the outpatient department of Nanjing Brain Hospital from 2023 to 2024, and 344 children and adolescents with typical development(TD) were recruited.All participants were matched in a ratio of 1∶1∶1 (ASD∶ADHD∶TD) according to gender and age, and 97 participants were included in each group for analysis.The Chinese version of the social skills improvement system rating scales(SSIS-RS-C) was used to evaluate social skills and problem behaviors, and autistic child behavior checklist(ABC), childhood autism rating scale(CARS), the Chinese version of the social communication questionnaire(SCQ) and the Chinese version of Swanson, Nolan, and Pelham, version Ⅳ scale-parent form(SNAP-Ⅳ) were used to evaluate the core symptoms of ASD and ADHD, respectively. SPSS 26.0 software was used to perform variance, Chi-square test, Spearman correlation analysis and multivariate Logistic regression analysis.Results:The social skills score of ASD group was lower than ADHD group ((61.53±24.26) vs (80.89±15.19), P<0.05), while the problem behavior score of ASD group was higher than ADHD group ((38.82±11.92) vs (34.00±12.45), P<0.05). In ASD group, the scores of ABC, CARS and SCQ were negatively correlated with the score of social skills ( r=-0.26--0.55, P<0.05). In ADHD group, the total score and each subscale of SNAP-Ⅳ were positively correlated with the score of problem behavior ( r=0.25-0.65, P<0.05). Multivariate Logistic regression analysis showed that empathy was a negative influencing factor of ASD ( B=-0.246, OR=0.782, P<0.05), and hyperactivity/inattention was a positive influencing factor of ASD ( B=0.589, OR=1.802, P<0.01), while only hyperactivity/inattention was a positive influencing factor of ADHD( B=0.779, OR=2.180, P<0.01). Conclusion:Children and adolescents with ASD and ADHD both have defects in social skills and problem behaviors, and these defects are associated with the core characteristics of their respective diseases.

Objective To investigate the feasibility and safety of bedside transesophageal echocardiography(TEE)-guided atrial septostomy in patients undergoing extracorporeal membrane oxygenation(ECMO)support.Methods Eight patients(2 females and 6 males)who developed pulmonary edema during VA-ECMO treatment between January 2020 and October 2024 were enrolled.All patients underwent bedside TEE-guided atrial septal puncture,followed by gradual balloon dilation using an Inoue balloon(diameter:18-24 mm).The endpoint for dilation was defined as mean left atrial pressure＜15 mmHg.Post-procedure evaluation included assessment of the septal defect size,mean left atrial pressure,and improvement in bilateral pulmonary edema.Results The mean age of all 8 patients was(43.50±16.84)years old.Atrial septostomy was successfully performed in all patients.The mean balloon dilation diameter was(22.75±2.68)mm,resulting in a mean septal defect size of(6.31±0.37)mm.The mean left atrial pressure significantly decreased from(26.63±1.77)mmHg pre-procedure to(12.75±1.28)mmHg post-procedure(P＜0.001).All patients demonstrated marked improvement in bilateral pulmonary edema,and six patients also showed a significant reduction in the severity of mitral regurgitation following the procedure.No procedure-related complications were observed.Conclusions Bedside TEE-guided atrial septostomy is safe and effective for reducing left heart loading during ECMO support and improving pulmonary edema.

Objective To explore current status and potential subtypes of elderly stroke patients' medication literacy among,and to analyze related influencing factors of different subtypes.Methods A total of 285 elderly stroke patients admitted in the First Affiliated Hospital of Zhengzhou University from November 2023 to June 2024 were selected as subjects.General Information questionnaire,medication literacy scale for elderly patients with chronic diseases,and perceived social support scale were conducted.Latent profile analysis(LPA)of elderly stroke patients' medication literacy was conducted,and Logistic regression analysis was used to explore influencing factors of different profiles.Results Score of medication literacy scale for elderly stroke patients was(48.26±12.51)points.Medication literacy among elderly stroke patients can be divided into 3 profiles,namely proactive-high literacy type(51.9％),balanced-medium literacy type(34.0％),and dependent-low literacy type(14.1％).Logistic regression analysis showed that recent medication types,current place of residence,educational level,diabetes,and social support were the influencing factors of elderly stroke patients' medication literacy(P＜0.05).Conclusion The level of medication literacy among elderly stroke patients is medium,which is characterized by 3 categories.Medical staffs targeted intervention should be adopted according to different category characteristics,so as to accurately meet their nursing needs,finally improve the level of elderly stroke patients' medication literacy.

Objective:To investigate the impact of different treatment sequences of immunotherapy combined with chemoradiotherapy (CRT) as the first-line therapy on the prognosis of patients with stage III non-small cell lung cancer (NSCLC).Methods:Clinical data of 112 patients with stage III NSCLC treated at the Fourth Hospital of Hebei Medical University from January 2019 to December 2021 were retrospectively collected, with follow-up continued until December 31, 2023. According to the sequence of CRT and immune checkpoint inhibitors (ICIs) therapy, patients were divided into 3 groups: ICIs simultaneous with CRT (sICR, n=20), chemotherapy combined with ICIs followed by CRT (CI-CR, n=53), and CRT followed by consolidative ICIs (CR-I, n=39). Analyses were performed before and after propensity score matching (PSM). Survival outcomes were assessed using the Kaplan-Meier method and compared by log-rank tests, and prognostic factors were identified through multivariate Cox regression analysis. Results:The median overall survival (OS) and progression-free survival (PFS) for the entire cohort were 30.1 months (95% CI: 21.4-38.9) and 12.8 months (95% CI: 9.14-16.1), respectively. Before PSM: No significant differences were observed in OS and PFS among the 3 groups ( χ2=0.18, 1.05; P=0.669, 0.305). However, OS in the sICR and CR-I groups was significantly better than that in the CI-CR group ( χ2=4.43, 6.11; P=0.035, 0.013). After PSM: Each group included 17 patients. There were no significant differences in OS or PFS among the 3 groups ( χ2=2.50, 2.74; P=0.287, 0.254), and pairwise comparisons also showed no significant differences. Multivariate Cox regression analysis revealed that clinical stage ( HR=3.392, 95% CI: 1.215-9.470, P=0.020), number of immunotherapy cycles ( HR=0.312, 95% CI: 0.100-0.972, P=0.044), and treatment response ( HR=6.566, 95% CI: 1.705-25.284, P=0.006) were independent prognostic factors for OS. After PSM, the numbers of patients with grade ≥2 treatment-related adverse events were 13 in the sICR group, 10 in the CI-CR group, and 9 in the CR-I group, with no significant differences among them ( χ2=2.181, P=0.336). Conclusions:First-line immunotherapy combined with chemoradiotherapy showed favorable clinical efficacy in locally advanced NSCLC compared to other studies, but the treatment sequence did not significantly affect prognosis. It is recommended that immunotherapy be administered for at least four cycles.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.