Objective To understand the experience of fall alertness in elderly patients with rheumatoid arthritis and to provide references for the development of targeted nursing intervention strategies.Methods 13 elderly patients with rheumatoid arthritis,who were admitted to the Department of Rheumatology and Immunology of a tertiary hospital in Guizhou Province from February to April 2024,were selected through purposive sampling.Phenomenological qualitative research methods were used,with semi-structured in-depth interviews.Data were analyzed using Colaizzi's seven-step method,and themes were extracted.Results 3 main themes and 9 sub-themes were identified:the process of fall risk perception(reshaping fall risk cognition,establishing emotional coping mechanism,enhancing fall alertness effect),behavioral responses to fall alertness(creating a safe living environment,regularizing daily routine plan),and needs for fall prevention support(need for fall prevention knowledge,home rehabilitation care needs,intelligent device usage needs,psychosocial support needs).Conclusion Clinical medical staff should pay attention to the transformation process of fall risk perception in elderly rheumatoid arthritis patients,accurately identify patients'fall support needs in practice,and guide patients to adopt appropriate fall alert response behaviors through innovative fall demand support interaction paths and the construction of social support network systems,in order to improve patients'fall alertness and reduce their fall risk.

The neonatal Fc receptor(FcRn)prolongs the half-life of immunoglobulin G(IgG)and promotes its recycling by binding to and making it an important receptor for maintaining serum IgG homeostasis.However,the abnormal accumulation of pathogenic IgG is closely related to the occurrence of various neuroimmune diseases.FcRn antagonists can significantly reduce the level of pathogenic IgG by blocking the binding of FcRn to IgG,thereby effectively alleviating the clinical symptoms of related diseases.As an emerging targeted therapeutic drug,FcRn antagonists have shown their potential in treating IgG-mediated neuroimmune diseases.This article summarizes the mechanism of action,types and clinical research progress of FcRn antagonists with the aim of providing new ideas for the precise treatment of IgG-mediated neuroimmune diseases.Future research should focus on the long-term safety of drugs,expansion of indications and individualized treatment strategies to further enhance their clinical application value.

Objective Nude mice xenograft model with aberrant activation of the PI3K/AKT pathway was established based on PIK3CA-overexpressing non-small cell lung cancer(NSCLC)cell lines PC-9,to observe the effect of Qingkailing injection combined with gefitinib on the growth of xenograft tumor in nude mice and explore its effects on ROS levels,mTOR pathway and STAT3 pathway.Methods After the xenografttumor model of BALB/c nude mice was established successfully,the mice were randomly divided into control group,Qingkailing injection group(10 mL·kg-1),gefitinib group(2.5 mg·kg-1),and Qingkailing combined with gefitinib group,with 5 mice in each group.They were administered for 32 days and then sacrificed.The tumor weight of each group was weighed and the tumor suppression rate was calculated;the level of ROS in the tumor tissues of each group was detected by flow cytometry;the protein levels of PI3K p110α,p-AKT and p-STAT3 in the xenograft tumor tissues of each group were detected by immunohistochemistry;the protein levels of the PI3K/AKT/mTOR pathway and the STAT3 pathway in the xenografttumor tissues of each group were detected by protein western blotting.Results Compared with the control group,Qingkailing injection could slow the tumor growth,significantly reduce the tumor weight,increase the level of ROS,and could significantly down-regulate the levels of PI3K p110α,AKT,mTOR,and STAT3 proteins in the tumor tissues(P<0.05);compared with the gefitinib single-agent group,the tumor growth of the Qingkailing combined with gefitinib group was slow,the weight of the tumors was significantly lower,and it also could significantly elevate the ROS level and downregulate the levels of PI3K p110α,AKT,mTOR,and STAT3 proteins in tumor tissues(P<0.05).Conclusion Qingkailing injection combined with gefitinib inhibited the growth of gefitinib-resistant xenograft in nude mice caused by abnormal activation of the PI3K/AKT pathway.Qingkailing injection may inhibit the PI3K/AKT pathway,its downstream mTOR pathway and STAT3 signaling pathway by up-regulating ROS levels,thereby enhancing the inhibitory effect of gefitinib on the proliferation of xenograft tumors of lung cancer xenografts in nude mice.

The incidence of apoplexy remains persistently high among the older population.Based on the traditional Chinese medicine principle of"treating the elderly by focusing on the fu",this paper explores the holistic connotation of"fu".It proposes that the onset of apoplexy in the elderly is characterized by obstruction,stagnation,depression,and sluggishness,which should be treated from six fu viscera,xuanfu,and collaterals.The interconnected hierarchical network of these three systems,serving as macro-and micro-channels for qi and fluid metabolism,plays a central role in both disease development and treatment.The failure of the six fu viscera to descend and the upward invasion of turbid yin are identified as prerequisites for apoplexy onset,whereas yang qi stagnation and xuanfu blockage act as key pathogenic drivers,and the core mechanisms involve phlegm-stasis-toxin accumulation,and dysfunction of the collaterals and fu.In the treatment,acute phase requires unblocking fu viscera and restoring xuanfu patency;chronic phase focuses on dredging collaterals and opening xuanfu;and recovery phase emphasizes tonifying combined with regulating xuanfu.The understanding of"treating the elderly by focusing on the fu"emphasizes that the pathogenesis of the disease should be changed to individual conditions;"six fu viscera-xuanfu-collaterals"exhibits a pathological mechanism characterized by the transmission and reception of pathogenic factors,as well as progressive mutual involvement;in clinical practice,treatment should meticulously assess the severity and nuances of the condition,prioritizing method that emphasizes unobstructed flow;additionally,therapy should be essential to protect stomach qi and integrate therapeutic attacks within a framework of supplementation.These principles offer valuable reference for the differentiation and treatment of apoplexy.

Objective:To evaluate the efficacy of peritoneal dialysis (PD) in the treatment of acute kidney injury (AKI) in critically ill neonates.Methods:It was a retrospective study. The baseline characteristic data, PD protocols, PD catheter placement methods and clinical outcomes of AKI neonates who underwent PD in the General Hospital of Ningxia Medical University between July 2015 and December 2024 were collected and analyzed.Results:(1) Among the 8 neonates with AKI, gestational age was (30.38±6.02) weeks, and birth weight was 1 397.5 (839.0, 2 312.5) g, with 6 premature infants. The time from birth to AKI onset was 144 (48, 294) hours. The leading cause of AKI was sepsis (6/8). The treatment time of PD was (93.12±37.20) hours. (2) Renal function recovery: After PD treatment, urine output was significantly increased ( Z=-3.29, P<0.001), and serum creatinine was significantly decreased ( t=2.66, P=0.032). (3) Hyperkalemia: Six out of 8 patients presented with hyperkalemia, which significantly decreased after PD treatment ( t=3.37, P=0.008). (4) Acid-base balance:Five out of 8 neonates had metabolic acidosis, and 3 of 5 neonates achieved basically complete correction (including lactic acidosis). There was no statistically significant difference in acid-base balance indicators before and after PD treatment (all P>0.05). (5) PD-related complications: Two out of 8 patients experienced peritoneal dialysate leakage, and no other PD-related complications occurred. (6) Outcomes: The hospital stay was 27.0 (8.0, 57.5) days. Four out of 8 neonates survived, while the other 4 neonates died after withdrawal of treatment. The primary cause was multiple organ failure. Conclusions:PD is a safe and effective treatment for neonatal AKI, facilitating early renal recovery and correction of electrolyte and acid-base imbalances.

Objective:To explore the clinical and genetic characteristics of X-linked intellectual disability associated with HUWE1 gene variants.Methods:A cases series study retrospectively analyzed the clinical data of 6 children with HUWE1 gene variants. The children were identified from the Third Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Henan University of Chinese Medicine, and Guangzhou Women and Children′s Medical Center of Guangzhou Medical University between April 2021 and July 2023.The data included sex, age, dysmorphic features, intellectual and motor development, seizure history, neuroimaging findings, family history, and genetic results was analyzed.Results:A total of 6 children, including 5 boys and 1 girl. The age of onset ranged from 1 day to 3 years. All children presented with varying degrees of intellectual disability, with or without motor developmental delay. Dysmorphic features were observed in 4 children, including microcephaly in 3 children. Short stature were observed in 3 children. One child was diagnosed with autism spectrum disorders and 1 child had seizures. Two boys had relevant maternal family histories of febrile seizures and mild intellectual disability, respectively. Abnormal neuroimaging findings were presented in 4 children, including cerebral dysplasia (1 child), prominent supratentorial ventricles (1 child), and mild white matter demyelination (2 children). Whole-exome sequencing identified 5 missense variants and 1 in-frame deletion variant. Five variants were novel and previously unreported (c.12290C>T, c.12701T>C, c.9875C>T, c.9641A>T and c.10313_10315del). The variants in 4 boys were maternally inherited, while the remaining 2 children had de novo variants. The child with the in-frame deletion variant (c.10313_10315del) presented with the most severe phenotype, exhibiting symptoms from 1 day of age, absent cognitive development, feeding difficulties, and congenital laryngeal chondrodysplasia. He was lost to follow-up at 3 months of age after treatment was withdrawn. The age at the last follow-up for the remaining 5 children ranged from 2 years and 10 months to 17 years. A boy with seizures died at 2 years and 10 months of age. The remaining 4 children were able to walk independently at the last follow-up, although their developmental progress was slow. Conclusions:HUWE1 gene related X-linked intellectual disability is characterized by varying degrees of developmental delay and intellectual disability, frequently accompanied by microcephaly, short stature, and occasionally by seizures and autism spectrum disorders. Missense variants are more common and the in-frame deletion variant appears to be associated with a particularly severe phenotypic presentation.

The incidence of apoplexy remains persistently high among the older population.Based on the traditional Chinese medicine principle of"treating the elderly by focusing on the fu",this paper explores the holistic connotation of"fu".It proposes that the onset of apoplexy in the elderly is characterized by obstruction,stagnation,depression,and sluggishness,which should be treated from six fu viscera,xuanfu,and collaterals.The interconnected hierarchical network of these three systems,serving as macro-and micro-channels for qi and fluid metabolism,plays a central role in both disease development and treatment.The failure of the six fu viscera to descend and the upward invasion of turbid yin are identified as prerequisites for apoplexy onset,whereas yang qi stagnation and xuanfu blockage act as key pathogenic drivers,and the core mechanisms involve phlegm-stasis-toxin accumulation,and dysfunction of the collaterals and fu.In the treatment,acute phase requires unblocking fu viscera and restoring xuanfu patency;chronic phase focuses on dredging collaterals and opening xuanfu;and recovery phase emphasizes tonifying combined with regulating xuanfu.The understanding of"treating the elderly by focusing on the fu"emphasizes that the pathogenesis of the disease should be changed to individual conditions;"six fu viscera-xuanfu-collaterals"exhibits a pathological mechanism characterized by the transmission and reception of pathogenic factors,as well as progressive mutual involvement;in clinical practice,treatment should meticulously assess the severity and nuances of the condition,prioritizing method that emphasizes unobstructed flow;additionally,therapy should be essential to protect stomach qi and integrate therapeutic attacks within a framework of supplementation.These principles offer valuable reference for the differentiation and treatment of apoplexy.

Objective To understand the experience of fall alertness in elderly patients with rheumatoid arthritis and to provide references for the development of targeted nursing intervention strategies.Methods 13 elderly patients with rheumatoid arthritis,who were admitted to the Department of Rheumatology and Immunology of a tertiary hospital in Guizhou Province from February to April 2024,were selected through purposive sampling.Phenomenological qualitative research methods were used,with semi-structured in-depth interviews.Data were analyzed using Colaizzi's seven-step method,and themes were extracted.Results 3 main themes and 9 sub-themes were identified:the process of fall risk perception(reshaping fall risk cognition,establishing emotional coping mechanism,enhancing fall alertness effect),behavioral responses to fall alertness(creating a safe living environment,regularizing daily routine plan),and needs for fall prevention support(need for fall prevention knowledge,home rehabilitation care needs,intelligent device usage needs,psychosocial support needs).Conclusion Clinical medical staff should pay attention to the transformation process of fall risk perception in elderly rheumatoid arthritis patients,accurately identify patients'fall support needs in practice,and guide patients to adopt appropriate fall alert response behaviors through innovative fall demand support interaction paths and the construction of social support network systems,in order to improve patients'fall alertness and reduce their fall risk.

ObjectiveTo investigate the effects of Scutellariae Radix combined with epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） on cell proliferation， apoptosis， cancer stem cell （CSC） marker expression， and metabolism in non-small cell lung cancer （NSCLC） cells. MethodsThe anti-tumor effects of Scutellariae Radix and EGFR-TKIs （gefitinib or osimertinib） in NSCLC cells were evaluated using the cell counting kit-8 （CCK-8） and Annexin V-FITC/propidium iodide （PI） double staining apoptosis assay. The activity of Scutellariae Radix and EGFR-TKIs in three-dimensional （3D） cultures of NSCLC cells was assessed using the CellTiter-Glo® 3D cell viability assay. The mRNA and protein expression levels of CSC markers， sex determining region y box protein 2 （SOX2） and aldehyde dehydrogenase 1 family member A1 （ALDH1A1）， were detected by quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot， respectively. Changes in intracellular reactive oxygen species （ROS） levels were detected by ROS staining， and the redox ratio was detected by femtosecond laser labeling free imaging （FLI）. ResultsUnder both two-dimensional （2D） and 3D culture conditions， compared with the blank group and EGFR-TKI group， the combination group showed significantly reduced cell viability and increased apoptosis rate （P<0.05）. Compared with the EGFR-TKI group， the mRNA and protein levels of CSC markers were significantly downregulated in the combination group （P<0.05）. Additionally， the redox ratio was significantly elevated （P<0.05）， and ROS levels were also increased in the combination group compared with the EGFR-TKI group. ConclusionIn NSCLC cells， Scutellariae Radix enhances the redox ratio and increases ROS levels， thereby inhibiting the expression of CSC markers and strengthening the anti-tumor effects of EGFR-TKIs. This provides a novel molecular mechanism by which Scutellariae Radix may enhance the sensitivity of targeted therapies.

BACKGROUND: G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA). METHODS: The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism. RESULTS: In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (T regs ), an increase in the cluster of differentiation 8 positive (CD8 + ) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8 + T cells, and induced the proportion of T regs . Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells. CONCLUSION Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cells in RA.
G-Protein-Coupled Receptor Kinase 2/metabolism* ; Arthritis, Rheumatoid/immunology* ; Animals ; Dendritic Cells/metabolism* ; Paroxetine/therapeutic use* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mice ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Lymphocyte Activation/drug effects* ; Female ; T-Lymphocytes/metabolism* ; Middle Aged